Skip to main content
SpringerLink
Log in

Site-Selective Reactions with Peptide-Based Catalysts

  • Chapter
  • First Online:
Book cover Site-Selective Catalysis

Part of the book series: Topics in Current Chemistry ((TOPCURRCHEM,volume 372))

Abstract

The problem of catalyst-controlled site-selectivity can potentially require a catalyst to overcome energetic barriers larger than those associated with enantioselective reactions. This challenge is a signature of substrates that present reactive sites that are not of equivalent reactivity. Herein we present a narrative of our laboratory’s efforts to overcome this challenge using peptide-based catalysts. We highlight the interplay between understanding the inherent reactivity preferences of a given target molecule and the development of catalysts that can overcome intrinsic preferences embedded within a substrate.

This is a preview of subscription content, log in via an institution to check access.

Access this chapter

Log in via an institution
Chapter
USD 29.95
Price excludes VAT (USA)
  • Available as PDF
  • Read on any device
  • Instant download
  • Own it forever
eBook
USD 169.00
Price excludes VAT (USA)
  • Available as EPUB and PDF
  • Read on any device
  • Instant download
  • Own it forever
Softcover Book
USD 219.99
Price excludes VAT (USA)
  • Compact, lightweight edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info
Hardcover Book
USD 219.99
Price excludes VAT (USA)
  • Durable hardcover edition
  • Dispatched in 3 to 5 business days
  • Free shipping worldwide - see info

Tax calculation will be finalised at checkout

Purchases are for personal use only

Institutional subscriptions

References

  1. Matsumoto M, Lee SJ, Gagne MR, Waters ML (2014) Cross-strand histidine-aromatic interactions enhance acyl-transfer rates in beta-hairpin peptide catalysts. Org Biomol Chem 12:8711–8718

    Article  CAS  Google Scholar 

  2. Matsumoto M, Lee SJ, Waters ML, Gagne MR (2014) A catalyst selection protocol that identifies biomimetic motifs from β-hairpin libraries. J Am Chem Soc 136:15817–15820

    Article  CAS  Google Scholar 

  3. Julia S, Masana J, Vega JC (1980) “Synthetic enzymes”. Highly stereoselective epoxidation of a chalcone in a triphasic toluene-water-poly[(S)-alanine] system. Angew Chem Int Ed 19:929–931

    Article  Google Scholar 

  4. Porter MJ, Roberts SM, Skidmore J (1999) Polyamino acids as catalysts in asymmetric synthesis. Bioorg Med Chem 7:2145–2156

    Article  CAS  Google Scholar 

  5. Jarvo ER, Miller SJ (2002) Amino acids and peptides as asymmetric organocatalysts. Tetrahedron 58:2481–2495

    Article  CAS  Google Scholar 

  6. Miller SJ (2004) In search of peptide-based catalysts for asymmetric organic synthesis. Acc Chem Res 37:601–610

    Article  CAS  Google Scholar 

  7. Colby Davie EA, Mennen SM, Xu Y, Miller SJ (2007) Asymmetric catalysis mediated by synthetic peptides. Chem Rev 107:5759–5812

    Article  CAS  Google Scholar 

  8. Wenemers H (2011) Asymmetric catalysis with peptides. Chem Commun 47:12036–12041

    Article  CAS  Google Scholar 

  9. Lewandowski B, Wennemers H (2014) Asymmetric catalysis with short-chain peptides. Curr Opin Chem Biol 22:40–46

    Article  CAS  Google Scholar 

  10. Kagan HB, Fiaud JC (1979) New approaches in asymmetric synthesis. In: Eliel EL, Allinger NL (eds) Topics in stereochemistry, vol 10. Wiley, Hoboken, pp 175–285

    Chapter  Google Scholar 

  11. Kagan HB, Fiaud JC (1988) Kinetic resolution. In: Eliel EL, Wilen SH (eds) Topics in stereochemistry, vol 18. Wiley, Hoboken, pp 249–330

    Chapter  Google Scholar 

  12. Fenwick DR, Kagan HB (1999) Asymmetric amplification. In: Denmark SE (ed) Topics in stereochemistry, vol 122. Wiley, Hoboken, pp 257–296

    Chapter  Google Scholar 

  13. Manning G, Whyte DB, Martinez R, Hunter T, Sudarsanam S (2002) The protein kinase complement of the human genome. Science 298:1912–1934

    Article  CAS  Google Scholar 

  14. Krebs EG (1983) Historical perspectives on protein phosphorylation and a classification system for protein kinases. Philos Trans R Soc Lond B Biol Sci 302:3–11

    Article  CAS  Google Scholar 

  15. Demchenko AV (ed) (2008) Handbook of chemical glycosylation: advances in stereoselectivity and therapeutic relevance. Wiley-VCH, Weinheim

    Google Scholar 

  16. Ernst B, Hart GW, Sinay P (2000) Protecting groups: effects on reactivity, glycosylation stereoselectivity, and coupling efficiency. In: Green LG, Ley SV (eds) Carbohydrates in chemistry and biology. Wiley-VCH, Weinheim

    Chapter  Google Scholar 

  17. Fischer E (1914) Über Phosphorsäureester des Methyl-glucosids und Theophyllin-glucosids. Ber Chem 47:3193–3205

    Article  CAS  Google Scholar 

  18. Moffatt JG, Khorana HG (1957) Carbodiimides. VII. Tetra-p-nitrophenyl pyrophosphate, a new phosphorylating agent. J Am Chem Soc 79:3741–3746

    Article  CAS  Google Scholar 

  19. Chambers RW, Moffatt JG, Khorana HG (1957) Nucleoside polyphosphates. IV. A new synthesis of guanosine-5′-phosphate. J Am Chem Soc 79:3747

    Article  CAS  Google Scholar 

  20. Sculimbrene BR, Miller SJ (2001) Discovery of a catalytic asymmetric phosphorylation through selection of a minimal kinase mimic: a concise total synthesis of D-myo-inositol-1-phosphate. J Am Chem Soc 123:10125–10126

    Article  CAS  Google Scholar 

  21. Sculimbrene BR, Morgan AJ, Miller SJ (2002) Enantiodivergence in small-molecule catalysis of asymmetric phosphorylation: concise total syntheses of the enantiomeric D-myo-inositol-1-phosphate and D-myo-inositol-3-phosphate. J Am Chem Soc 124:11653–11656

    Article  CAS  Google Scholar 

  22. Sculimbrene BR, Morgan AJ, Miller SJ (2003) Nonenzymatic peptide-based catalytic asymmetric phosphorylation of inositol derivatives. Chem Commun 1781–1785

    Google Scholar 

  23. Agranoff BW, Fisher SK (1991) Inositol phosphates and derivatives: synthesis, biochemistry, and therapeutic potential. In Reitz AB (ed) ACS Symposium series 463, American Chemical Society, Washington, p 20

    Google Scholar 

  24. Billington DC (1993) The inositol phosphates: chemical synthesis and biological significance. VCH, New York

    Google Scholar 

  25. Pirrung MC (1999) Histidine kinases and two-component signal transduction systems. Chem Biol 121:11638–11643

    Google Scholar 

  26. Kee JM, Muir TW (2012) Chasing phosphohistidine, an elusive sibling in the phosphoamino acid family. ACS Chem Biol 7:44–51

    Article  CAS  Google Scholar 

  27. Copeland GT, Miller SJ (2001) Selection of enantioselective acyl transfer catalysts from a pooled peptide library through a fluorescence-based activity assay: an approach to kinetic resolution of secondary alcohols of broad structural scope. J Am Chem Soc 123:6496–6502

    Article  CAS  Google Scholar 

  28. Jarvo ER, Copeland GT, Papaioannou N, Bonitatebus PJ, Miller SJ (1999) A biomimetic approach to asymmetric acyl transfer catalysis. J Am Chem Soc 121:11638–11643

    Article  CAS  Google Scholar 

  29. Billington DC, Baker R, Kulagowski JJ, Mawer IM, Vacca JP, deSolms SJ, Huff JR (1989) The total synthesis of myo-inositol phosphates via myo-inositol orthoformate. J Chem Soc Perkin Trans 1:1423–1429

    Article  Google Scholar 

  30. Irvine RF, Schell MJ (2001) Back in the water: the return of the inositol phosphates. Nat Rev Mol Cell Biol 2:327–338

    Article  CAS  Google Scholar 

  31. Prestwich GD (2004) Phosphoinositide signaling: from affinity probes to pharmaceutical targets. Chem Biol 11:619–637

    Article  CAS  Google Scholar 

  32. Di Paolo G, de Camilli P (2006) Phosphoinositides in cell regulation and membrane dynamics. Nature 443:651–657

    Article  CAS  Google Scholar 

  33. Sculimbrene BR, Xu Y, Miller SJ (2004) Asymmetric syntheses of phosphatidylinositol-3-phosphates with saturated and unsaturated side chains through catalytic asymmetric phosphorylation. J Am Chem Soc 126:13182–13183

    Article  CAS  Google Scholar 

  34. Morgan AJ, Wang YK, Roberts MF, Miller SJ (2004) Chemistry and biology of deoxy-myo-inositol phosphates: stereospecificity of substrate interactions within an archaeal and a bacterial IMPase. J Am Chem Soc 126:15370–15371

    Article  CAS  Google Scholar 

  35. Morgan AJ, Komiya S, Xu Y, Miller SJ (2006) Unified total syntheses of the inositol polyphosphates: D-I-3,5,6P3, D-I-3,4,5P3, and D-I-3,4,5,6P4 via catalytic enantioselective and site-selective phosphorylation. J Org Chem 71:6923–6931

    Article  CAS  Google Scholar 

  36. Xu Y, Sculimbrene BR, Miller SJ (2006) Streamlined synthesis of phosphatidylinositol (PI), PI3P, PI3,5P2, and deoxygenated analogues as potential biological probes. J Org Chem 71:4919–4928

    Article  CAS  Google Scholar 

  37. Longo CM, Wei Y, Roberts MF, Miller SJ (2009) Asymmetric syntheses of L, L- and L, D-di-myo-inositol-1,1′-phosphate and their behavior as stabilizers of enzyme activity at extreme temperatures. Angew Chem Int Ed 48:4158–4161

    Article  CAS  Google Scholar 

  38. Cuilla R, Burrgraf S, Stetter KO, Roberts MF (1994) Occurrence and role of di-myo-inositol-1,1′-phosphate in Methanococcus igneus. Appl Environ Microbiol 60:3660–3664

    Google Scholar 

  39. Chen L, Spiliotis ET, Roberts MF (1998) Biosynthesis of di-myo-inositol-1,1′-phosphate, a novel osmolyte in hyperthermophilic Archaea. J Bacteriol 180:3785–3792

    CAS  Google Scholar 

  40. Chandler BD, Burkhardt AL, Foley K, Cullis C, Driscoll D, D’Amore NR, Miller SJ (2014) A fully synthetic and biochemically validated phosphatidyl inositol-3-phosphate hapten via asymmetric synthesis and native chemical ligation. J Am Chem Soc 136:412–418

    Article  CAS  Google Scholar 

  41. Harris JR, Markl J (1999) Keyhole limpet hemocyanin (KLH): a biomedical review. Micron 6:597–623

    Article  Google Scholar 

  42. Harlow E, Lane D (1988) Antibodies: a laboratory manual. Cold Spring Harbor, New York, Chapter 5

    Google Scholar 

  43. Hermanson GT (2008) Bioconjugate techniques, 2nd edn. Academic, New York, Chapter 19

    Google Scholar 

  44. Martin SF, Josey JA, Wong YL, Dean DW (1994) General method for the synthesis of phospholipid derivatives of 1,2-O-diacyl-sn-glycerols. J Org Chem 59:4805–4820

    Article  CAS  Google Scholar 

  45. Dawson PE, Muir TW, Clark-Lewis I, Kent SBH (1994) Synthesis of proteins by native chemical ligation. Science 266:776–779

    Article  CAS  Google Scholar 

  46. Johnson ECB, Kent SBH (2006) Insights into the mechanism and catalysis of the native chemical ligation reaction. J Am Chem Soc 128:6640–6646

    Article  CAS  Google Scholar 

  47. Nilsson BL, Soellner MB, Raines RT (2005) Chemical synthesis of proteins. Annu Rev Biophys Biomol Struct 34:91–118

    Article  CAS  Google Scholar 

  48. Fang GM, Cui HK, Zheng JS, Liu L (2010) Chemoselective ligation of peptide phenyl esters with N-terminal cysteines. ChemBioChem 11:1061–1065

    Article  CAS  Google Scholar 

  49. Lewis CA, Sculimbrene BR, Xu Y, Miller SJ (2005) Desymmetrization of glycerol derivatives with peptide-based acylation catalysts. Org Lett 7:3021–3023

    Article  CAS  Google Scholar 

  50. Griswold KS, Miller SJ (2003) A peptide-based catalyst approach to regioselective functionalization of carbohydrates. Tetrahedron 59:8869–8875

    Article  CAS  Google Scholar 

  51. Evans JW, Fierman MB, Miller SJ, Ellman JA (2004) Catalytic enantioselective synthesis of sulfinate esters through the dynamic resolution of tert-butanesulfinyl chloride. J Am Chem Soc 126:8134–8135

    Article  CAS  Google Scholar 

  52. Schreiber SL, Schreiber TS, Smith DB (1987) Reactions that proceed with a combination of enantiotopic group and diastereotopic face selectivity can deliver products with very high enantiomeric excess: experimental support of a mathematical model. J Am Chem Soc 109:1525–1529

    Article  CAS  Google Scholar 

  53. Kawabata T, Nagato M, Takasu K, Fuji K (1997) Nonenzymatic kinetic resolution of racemic alcohols through an “induced fit” process. J Am Chem Soc 119:3169–3170

    Article  CAS  Google Scholar 

  54. Kawabata T, Yamamoto K, Momose Y, Yoshida H, Nagaoka Y, Fuji K (2001) Kinetic resolution of amino alcohol derivatives with a chiral nucleophilic catalyst: access to enantiopure cyclic cis-amino alcohols. Chem Commun 2700–2701

    Google Scholar 

  55. Kawabata T, Muramatsu W, Nishio T, Shibata T, Schedel H (2007) A catalytic one-step process for the chemo- and regioselective acylation of monosaccharides. J Am Chem Soc 129:12890–12895

    Article  CAS  Google Scholar 

  56. Ueda Y, Muramatsu W, Mishiro K, Furuta T, Kawabata T (2009) Functional group tolerance in organocatalytic regioselective acylation of carbohydrates. J Org Chem 74:8802–8805

    Article  CAS  Google Scholar 

  57. Williamson CL, Chan L, Taylor MS (2012) Regioselective, borinic acid-catalyzed monoacylation, sulfonylation, and alkylation of diols and carbohydrates: expansion of substrate and mechanistic studies. J Am Chem Soc 134:8260–8267

    Article  CAS  Google Scholar 

  58. Taylor MS (2015) Catalysis based on reversible covalent interactions of organoboron compounds. Acc Chem Res 48:295–305

    Article  CAS  Google Scholar 

  59. Sun X, Lee H, Lee S, Tan KL (2013) Catalyst recognition of cis-1,2-diols enables site-selective functionalization of complex molecules. Nat Chem 5:790–795

    Article  CAS  Google Scholar 

  60. Manville N, Alite H, Haeffner F, Hoveyda AH, Snapper ML (2013) Enantioselective silyl protection of alcohols promoted by a combination of chiral and achiral Lewis basic catalysts. Nat Chem 5:768–774

    Article  CAS  Google Scholar 

  61. Blaisdell TP, Lee S, Kasaplar P, Sun X, Tan KL (2013) Practical silyl protection of ribonucleosides. Org Lett 15:4710–4713

    Article  CAS  Google Scholar 

  62. Sun X, Worthy AD, Tan KL (2013) Resolution of terminal 1,2-diols via silyl transfer. J Org Chem 78:10494–10499

    Article  CAS  Google Scholar 

  63. Sun X, Lee H, Lee S, Tan KL (2013) Catalyst recognition of cis-1,2-diols enables site-selective functionalization of complex molecules. Nature Chem 5:790–795

    Article  CAS  Google Scholar 

  64. Zhao Y, Rodrigo J, Hoveyda AH, Snapper ML (2006) Enantioselective silyl protection of alcohols catalysed by amino-acid-based small molecule. Nature 443:64–70

    Article  CAS  Google Scholar 

  65. Rawlings BJ (1999) Biosynthesis of polyketides (other than actinomycete macrolides). Nat Prod Rep 16:425–484

    Article  CAS  Google Scholar 

  66. Shen B (2000) Biosynthesis of aromatic polyketides. Top Curr Chem 209:1–51

    Article  CAS  Google Scholar 

  67. Newman DJ, Cragg GM (2007) Natural products as sources of new drugs over the last 25 years. J Nat Prod 70:461–477

    Article  CAS  Google Scholar 

  68. Walsh CT (2008) The chemical versatility of natural product assembly lines. Acc Chem Res 41:4–10

    Article  CAS  Google Scholar 

  69. Cragg GM, Newman DJ (2013) Natural products: a continuing source of novel drug leads. Biochim Biophys Acta 1830:3670–3695

    Article  CAS  Google Scholar 

  70. Hertweck C (2009) The biosynthetic logic of polyketide diversity. Angew Chem Int Ed 48:4688–4716

    Article  CAS  Google Scholar 

  71. Schetter B, Mahrwald R (2006) Modern aldol methods for the total synthesis of polyketides. Angew Chem Int Ed 45:7506–7525

    Article  CAS  Google Scholar 

  72. Dechert-Schmitt AMR, Schmitt DC, Gao X, Itoh T, Krische MJ (2014) Polyketide construction via hydrohydroxyalkylation and related alcohol C-H functionalizations. Reinventing the chemistry of carbonyl addition. Nat Prod Rep 31:504–513

    Article  CAS  Google Scholar 

  73. Dalby SM, Paterson I (2010) Synthesis of polyketide natural products and analogs as promising anticancer agents. Curr Opin Drug Discov Devel 13:777–794

    CAS  Google Scholar 

  74. Cane DE, Walsh CT, Khosla C (1998) Harnessing the biosynthetic code: combinations, permutations, and mutations. Science 282:63–68

    Article  CAS  Google Scholar 

  75. Khosla C, Herschlag D, Cane DE, Walsh CT (2014) Assembly line polyketide synthases: mechanistic insights and unsolved problems. Biochemistry 53:2875–2883

    Article  CAS  Google Scholar 

  76. Hutchinson CR, Fuji I (1995) Polyketide synthase gene manipulation: a structure-function approach in engineering novel antibiotics. Annu Rev Microbiol 49:201–238

    Article  CAS  Google Scholar 

  77. Jacobsen JR, Hutchinson CR, Cane DE, Khosla C (1997) Precursor-directed biosynthesis of erythromycin analogs by an engineered polyketide synthase. Science 277:367–369

    Article  CAS  Google Scholar 

  78. Hertweck C (2015) Decoding and reprogramming complex polyketide assemblylines: prospects for synthetic biology. Trends Biochem Sci 40:189–199

    Article  CAS  Google Scholar 

  79. Wiley PF, Gerzon K, Flynn EH, Sigal MV, Weaver O, Quarck UC, Chauvette RR, Monahan R (1957) Erythromycin. X. Structure of erythromycin. J Am Chem Soc 79:6062–6070

    Article  CAS  Google Scholar 

  80. Kim JW, Adachi H, Kazuo SY, Hayakwa Y, Seto H (1997) Apoptolidin, a new apoptosis inducer in transformed cells from Nocardiopsis sp. J Antibiot 50:628–630

    Article  CAS  Google Scholar 

  81. Taylor RE, Chen Y, Galvin GM, Prabba PK (2004) Conformation-activity relationships in polyketide natural products. Towards to biologically active conformation of epothilone. Org Biomol Chem 2:127–132

    Article  CAS  Google Scholar 

  82. Larsen EM, Wilson MR, Taylor RE (2015) Conformation-activity relationships of polyketide natural products. Nat Prod Rep 32:1183–1206

    Article  CAS  Google Scholar 

  83. Wright GD (2005) Bacterial resistance to antibiotics: enzymatic degradation and modification. Adv Drug Deliv Rev 57:1451–1470

    Article  CAS  Google Scholar 

  84. Walsh CT (2005) Molecular mechanisms that confer antibacterial drug resistance. Nature 406:775–781

    Article  Google Scholar 

  85. Peddibhotia S, Dang Y, Liu JO, Romo D (2007) Simultaneous arming and structure/activity studies of natural products employing O-H insertions: an expedient and versatile strategy for natural products-based chemical genetics. J Am Chem Soc 129:12222–12231

    Article  CAS  Google Scholar 

  86. Robles O, Romo D (2014) Chemo- and site-selective derivatizations of natural products enabling biological studies. Nat Prod Rep 31:318–334

    Article  CAS  Google Scholar 

  87. Lewis CA, Miller SJ (2006) Site-selective derivatization and remodeling of erythromycin A by using simple peptide-based chiral catalysts. Angew Chem Int Ed 45:5616–5619

    Article  CAS  Google Scholar 

  88. Lewis CA, Merkel J, Miller SJ (2008) Catalytic site-selective synthesis and evaluation of a series of erythromycin analogs. Bioorg Med Chem Lett 18:6007–6011

    Article  CAS  Google Scholar 

  89. Jones PH, Perun TJ, Rowley EK, Baker EJ (1972) Chemical modifications of erythromycin antibiotics. 3. Synthesis of 4″ and 11 esters of erythromycin A and B. J Med Chem 15:631–634

    Article  CAS  Google Scholar 

  90. Martin YC, Jones PH, Perun TJ, Grundy WE, Bell S, Bower RR, Shipkowitz NL (1972) Chemical modification of erythromycin antibiotics. 4. Structure-activity relations of erythromycin esters. J Med Chem 15:635–638

    Article  CAS  Google Scholar 

  91. Haque TS, Little JC, Gellman SH (1994) ‘Mirror image’ reverse turns promote β-hairpin formation. J Am Chem Soc 116:4105–4106

    Article  CAS  Google Scholar 

  92. Haque TS, Little JC, Gellman SH (1996) Stereochemical requirements for β-hairpin formation: model studies with four-residue peptides and depsipeptides. J Am Chem Soc 118:6975–6985

    Article  CAS  Google Scholar 

  93. Gellman SH (1998) Minimal models systems for β-sheet secondary structure in proteins. Curr Opin Chem Biol 2:717–725

    Article  CAS  Google Scholar 

  94. Davies JS, Everett JR, Hatton IK, Hunt E, Tyler JW, Zomaya II, Slawin AMZ, Williams DJ (1991) NMR spectroscopic and X-ray crystallographic studies on the structure, stereochemistry and conformation of a series of 9,11 cyclic aminals of (9S)-9-N-methylerythromyclamine A. J Chem Soc Perkin Trans 2:201–214

    Article  Google Scholar 

  95. Everett JR, Hunt E, Tyler JW (1991) Ketone-hemiacetal tautomerism in erythromycin A in non-aqueous solutions. An NMR spectroscopic study. J Chem Soc Perkin Trans 2:1481–1487

    Article  Google Scholar 

  96. Tardrew PL, Mao JCH, Kenney D (1969) Antibacterial activity of 2′esters of erythromycin. Appl Microbiol 18:159–165

    CAS  Google Scholar 

  97. Lewis CA, Longcore KE, Miller SJ, Wender PA (2009) An approach to the site-selective diversification of apoptolidin A with peptide-based catalysts. J Nat Prod 72:1864–1869

    Article  CAS  Google Scholar 

  98. Wender PA, Gulledge AV, Jankowski OD, Seto H (2002) Isoapoptolidin: structure and activity of the ring-expanded isomer of apoptolidin. Org Lett 4:3819–3822

    Article  CAS  Google Scholar 

  99. Pennington JD, Williams HJ, Salomon AR, Sulikowski GA (2002) Toward a stable apoptolidin derivative: identification of isoapoptolidin and selective deglycosylation of apoptolidin. Org Lett 4:3823–3825

    Article  CAS  Google Scholar 

  100. Wender PA, Jankowski OD, Longcore K, Tabet EA, Seto H, Tomikawa T (2006) Correlation of F0F1-ATPase inhibition and antiproliferative activity of apoptolidin analogues. Org Lett 8:589–592

    Article  CAS  Google Scholar 

  101. Linnane P, Magnus N, Magnus P (1997) Induction of molecular asymmetry by a remote chiral group. Nature 385:799–801

    Article  CAS  Google Scholar 

  102. Clayden J, Lund A, Vallverdu L, Helliwell M (2004) Ultra-remote stereocontrol by conformational communication of information along a carbon chain. Nature 431:966–971

    Article  CAS  Google Scholar 

  103. Byrne L, Sola J, Boddaert T, Marcelli T, Adams RW, Morris GA, Clayden J (2014) Foldamer-mediated remote stereocontrol: >1,60 asymmetric induction. Angew Chem Int Ed 53:151–155

    Article  CAS  Google Scholar 

  104. Lewis CA, Chiu A, Kubryk M, Balsells J, Pollard D, Esser CK, Murry J, Reamer RA, Hansen KB, Miller SJ (2006) Remote desymmetrization at near-nanometer group separation catalyzed by a miniaturized enzyme mimic. J Am Chem Soc 128:16454–16455

    Article  CAS  Google Scholar 

  105. Lewis CA, Gustafson JL, Chiu A, Balsells J, Pollard D, Murry J, Reamer RA, Hansen KB, Miller SJ (2008) A case of remote asymmetric induction in the peptide-catalyzed desymmetrization of a bis(phenol). J Am Chem Soc 130:16358–16455

    Article  CAS  Google Scholar 

  106. Hoveyda A, Evans DA, Fu GC (1993) Substrate-directable chemical reactions. Chem Rev 93:1307–1370

    Article  CAS  Google Scholar 

  107. Yoshimoto FK, Guengerich FP (2014) Mechanism of the third oxidative step in the conversion of androgens to estrogens by cytochrome P450 19A1 steroid aromatase. J Am Chem Soc 136:15016–15025

    Article  CAS  Google Scholar 

  108. Pallan PS, Nagy LD, Li L, Gonzalez E, Kramlinger VM, Azumaya CM, Waterman MR, Guengerich FP, Egli M, Wawrzak Z (2015) Structural and kinetic basis of steroid 17α,20-lyase activity in teleost fish cytochrome P450 17A1 and its absence in cytochrome P450 17A2. J Biol Chem 290:3248–3268

    Article  CAS  Google Scholar 

  109. Payne AH, Hales DB (2004) Overview of steroidogenic enzymes in the pathway from cholesterol to active steroid hormones. Endocr Rev 25:947–970

    Article  CAS  Google Scholar 

  110. Barton DHR, McCombie SW (1975) A new method for the deoxygenation of secondary alcohols. J Chem Soc Perkin Trans 1:1574–1585

    Article  Google Scholar 

  111. Barton DHR, Blundell P, Dorchak J, Jang DO, Jaszberenyi J (1991) The invention of radical reactions. Part XXI. Simple methods for the radical deoxygenation of primary alcohols. Tetrahedron 47:8969–8984

    Article  CAS  Google Scholar 

  112. Barton DHR, Dorchak J, Jaszberenyi J (1992) The invention of radical reactions. Part XXIV. Relative rates of acylation and radical deoxygenation of secondary alcohols. Tetrahedron 48:7435–7446

    Article  CAS  Google Scholar 

  113. Sanchez-Rosello M, Puchlopek ALA, Morgan AJ, Miller SJ (2008) Site-selective catalysis of phenyl thionoformate transfer as a tool for regioselective deoxygenation of polyols. J Org Chem 73:1774–1782

    Article  CAS  Google Scholar 

  114. Jordan PA, Kayser-Bricker KJ, Miller SJ (2010) Asymmetric phosphorylation through catalytic P(III) phosphoramidite transfer: enantioselective synthesis of D-myo-inositol-6-phosphate. Proc Natl Acad Sci U S A 107:20620–20624

    Article  CAS  Google Scholar 

  115. Sculimbrene BR (2004). Catalytic asymmetric phosphorylation. Ph.D. thesis. Boston College, Boston

    Google Scholar 

  116. Carruthers MH (1991) Chemical synthesis of DNA and DNA analogs. Acc Chem Res 24:278–284

    Article  Google Scholar 

  117. Vlasuk GP, Webb TR, Abelman MM, Pearson DA, Miller TA (21, 1999) US Patent 5492895

    Google Scholar 

  118. Hayakawa Y, Katoka M (1997) Preparation of short oligonucleotides via the phosphoramidite method using a tetrazole promoter in a catalytic manner. J Am Chem Soc 119:11758–11762

    Article  CAS  Google Scholar 

  119. Jordan PA, Miller SJ (2012) An approach to the site-selective deoxygenation of hydroxyl groups based on catalytic phosphoramidite transfer. Angew Chem Int Ed 51:2907–2911

    Article  CAS  Google Scholar 

  120. Zhang L, Koreeda M (2004) Radical deoxygenation of hydroxyl groups via phosphites. J Am Chem Soc 126:13190–13191

    Article  CAS  Google Scholar 

  121. Fiori KW, Puchlopek ALA, Miller SJ (2009) Enantioselective sulfonylation reactions mediated by a tetrapeptide catalyst. Nat Chem 1:630–634

    Article  CAS  Google Scholar 

  122. Butler MS, Hansford KA, Blaskovich MAT, Halai R, Cooper MA (2014) Glycopeptide antibiotics: back to the future. J Antibiot 67:631–644

    Article  CAS  Google Scholar 

  123. Hubbard BK, Walsh CT (2003) Vancomycin assembly: nature’s way. Angew Chem Int Ed 42:730–765

    Article  CAS  Google Scholar 

  124. Nicolaou KC, Boddy CNC, Brase S, Winissinger N (1999) Chemistry, biology, and medicine of the glycopeptide antibiotics. Angew Chem Int Ed 38:2097–2152

    CAS  Google Scholar 

  125. Williams DH (1996) The glycopeptide story – how to kill the deadly ‘superbugs.’. Nat Prod Rep 13:469–477

    Article  CAS  Google Scholar 

  126. Min G, Chen Z, Onishi HR, Kohler J, Silver LL, Kerns R, Fukuzawa S, Thompson C, Kahne D (1999) Vancomycin derivatives that inhibit peptidoglycan biosynthesis without binding D-Ala-D-Ala. Science 284:507–511

    Article  Google Scholar 

  127. Kerns R, Dong SD, Fukuzawa S, Carbeck J, Kohler J, Silver LL, Kahne D (2000) The role of hydrophobic substituents in the biological activity of glycopeptide antibiotics. J Am Chem Soc 122:12608–12609

    Article  CAS  Google Scholar 

  128. Sun B, Chen Z, Eggert US, Shaw SJ, LaTour JV, Kahne D (2001) Hybrid glycopeptide antibiotics. J Am Chem Soc 123:12722–12723

    Article  CAS  Google Scholar 

  129. Lin H, Walsh CT (2004) A chemoenzymatic approach to glycopeptide antibiotics. J Am Chem Soc 126:13998–14003

    Article  CAS  Google Scholar 

  130. Leimkuhler C, Chen L, Barrett D, Panzone G, Sun B, Falcone B, Oberthuer M, Walker S, Kahne D (2005) Differential inhibition of Staphylococcus aureus PBP2 by glycopeptide antibiotics. J Am Chem Soc 127:3250–3251

    Article  CAS  Google Scholar 

  131. Ashford PA, Bew SP (2012) Recent advances in the synthesis of new glycopeptide antibiotics. Chem Soc Rev 41:957–978

    Article  CAS  Google Scholar 

  132. Higgins DL, Chang R, Debabov DV, Leung J, Wu T, Krause KM, Sandvik E, Hubbard JM, Kaniga K, Schmidt DE et al (2005) Telavancin, a multifunctional lipoglycopeptide, disrupts both cell wall synthesis and cell membrane integrity in methicillin-resistant Staphylococcus aureus. Antimicrob Agents Chemother 49:1127–1134

    Article  CAS  Google Scholar 

  133. Zhanel GC, Calic D, Schweizer F, Zelenitsky S, Adam H, Lagace-Wiens PRS, Rubinstein E, Gin AS, Hoban DJ, Karlowsky JA (2010) New lipoglycopeptides: a comparative review of dalbavancin, oritavancin, and telavancin. Drugs 70:859–886

    Article  CAS  Google Scholar 

  134. Reynolds PE (1989) Structure, biochemistry, and mechanism of action of glycopeptide antibiotics. Eur J Clin Microbiol Infect Dis 8:943–950

    Article  CAS  Google Scholar 

  135. Mackay JP, Gerhard U, Beauregard DA, Williams DH, Westwell MS, Searle MS (1994) Glycopeptide antibiotic activity and the possible role of dimerization: a model for biological signaling. J Am Chem Soc 116:4581–4590

    Article  CAS  Google Scholar 

  136. Dong SD, Oberthuer M, Losey HC, Anderson JW, Eggert US, Peczuh MW, Walsh CT, Kahne D (2002) The structural basis for induction of VanB resistance. J Am Chem Soc 124:9064–9065

    Article  CAS  Google Scholar 

  137. McComas CC, Crowley BM, Boger DL (2003) Partitioning the loss in vancomycin binding affinity or D-Ala-D-Lac into lost H-bond and repulsive lone pair contributions. J Am Chem Soc 125:9314–9315

    Article  CAS  Google Scholar 

  138. Crowley BM, Boger DL (2006) Total synthesis and evaluation of [Ψ[CH2NH]Tpg4]vancomycin aglycon: reengineering vancomycin for dual D-Ala-D-Ala and D-Ala-D-Lac binding. J Am Chem Soc 128:2885–2892

    Article  CAS  Google Scholar 

  139. Xie J, Pierce JG, James RC, Okano A, Boger DL (2011) A redesigned vancomycin engineered for dual D-Ala-D-Ala and D-Ala-D-Lac binding exhibits potent antimicrobial activity against vancomycin-resistant bacteria. J Am Chem Soc 133:13946–13949

    Article  CAS  Google Scholar 

  140. Xie J, Okano A, Pierce JG, James RC, Stamm S, Crane CM, Boger DL (2012) Total synthesis of [Ψ[C(═S)NH]Tpg4]vancomycin aglycon, [Ψ[C(═NH)NH]Tpg4]vancomycin aglycon, and related key compounds: reengineering vancomycin for dual D-Ala-D-Ala and D-Ala-D-Lac binding. J Am Chem Soc 134:1284–1297

    Article  CAS  Google Scholar 

  141. Bugg TDH, Wright GD, Dutka-Malen S, Arthur M, Courvalin P, Walsh CT (1991) Molecular basis for vancomycin resistance in Enterococus faecium BM4147: biosynthesis of a depsipeptide peptidoglycan precursor by vancomycin resistance proteins VanH and VanA. Biochemistry 30:10408–10415

    Article  CAS  Google Scholar 

  142. Walsh CT, Fisher SL, Park IS, Prahalad M, Wu Z (1996) Bacterial resistance to vancomycin: five genes and one missing hydrogen bond tell the story. Chem Biol 3:21–28

    Article  CAS  Google Scholar 

  143. Walsh CT (1993) Vancomycin resistance: decoding the molecular logic. Science 261:308–309

    Article  CAS  Google Scholar 

  144. Gray KC, Palacios DS, Dailey I, Endo MM, Uno BE, Wilcock BC, Burke MD (2012) Amphotericin primarily kills yeast by simply binding ergosterol. Proc Natl Acad Sci U S A 109:2234–2239

    Article  CAS  Google Scholar 

  145. Hanessian S, Giguere A, Grzyb J, Maianti JP, Saavedra OM, Aggen JB, Linsell MS, Goldblum AA, Hildebrandt DJ, Kane TR, Dozzo P, Gliedt MJ, Matias RD, Feeney LA, Armstrong ES (2011) Toward overcoming Staphylococcus aureus aminoglycoside resistance mechanism with a functionally designed neomycin analogue. ACS Med Chem Lett 2:924–928

    Article  CAS  Google Scholar 

  146. Szpilman AM, Cereghetti DM, Manthorpe JM, Wurtz NR, Carreira EM (2009) Synthesis and biophysical studies on 35-deoxy amphotericin B methyl ester. Chem Eur J 15:7117–7128

    Article  CAS  Google Scholar 

  147. Fujisawa KL, Hoshiya T, Kawaguchi H (1974) Aminoglycoside antiobiotics. VII. Acute toxicity of aminoglycoside antibiotics. J Antibiot 27:677–681

    Article  CAS  Google Scholar 

  148. Griffith BR, Krepel C, Fu X, Blanchard S, Ahmed A, Edmiston CE, Thorson JS (2007) Model for antibiotic optimization via neoglycosylation: synthesis of liponeoglycopeptides active against VRE. J Am Chem Soc 129:8150–8155

    Article  CAS  Google Scholar 

  149. Thompson C, Ge M, Kahne D (1999) Synthesis of vancomycin from the aglycon. J Am Chem Soc 121:1237–1244

    Article  CAS  Google Scholar 

  150. Fowler BS, Lammerhold KM, Miller SJ (2012) Catalytic site-selective thiocarbonylations and deoxygenations of vancomycin reveal hydroxy-dependent conformational effects. J Am Chem Soc 134:9755–9761

    Article  CAS  Google Scholar 

  151. Yoganathan S, Miller SJ (2015) Structure diversificiation of vancomycin through peptide-catalyzed, site-selective lipidation: a catalysis-based approach to combat glycopeptide-resistant pathogens. J Med Chem 58:2367–2377

    Article  CAS  Google Scholar 

  152. Fowler BS, Mikochik PJ, Miller SJ (2010) Peptide-catalyzed kinetic resolution of formamides and thioformamides as an entry to nonracemic amines. J Am Chem Soc 132:2870–2871

    Article  CAS  Google Scholar 

  153. Han S, Miller SJ (2013) Asymmetric catalysis at a distance: catalytic, site-selective phosphorylation of teicoplanin. J Am Chem Soc 135:12414–12421

    Article  CAS  Google Scholar 

  154. Han S, Le BV, Hajare HS, Baxter RHG, Miller SJ (2014) X-Ray crystal structure of teicoplanin-A2-2 bound to a catalytic peptide sequence via the carrier protein strategy. J Org Chem 79:8550–8556

    Article  CAS  Google Scholar 

  155. Chan HC, Huang YT, Lyu SY, Huang CJ, Li YS, Liu YC, Chou CC, Tsai MD, Li TL (2011) Regioselective deacetylation based on teicoplanin-complexed Orf2* crystal structures. Mol Biosyst 7:1224–1231

    Article  CAS  Google Scholar 

  156. Nieto M, Perkins HR (1971) The specificity of combination between ristocetins and peptides related to bacterial cell-wall mucopeptide precursors. Biochem J 124:845–852

    Article  CAS  Google Scholar 

  157. Economou NJ, Zentner IJ, Lazo E, Jakonicic J, Stojanoff V, Weeks SD, Gratsky KC, Cocklin S, Loll PJ (2013) Structure of the complex between teicoplanin and a bacterial cell-wall peptide: use of a carrier-protein approach. Acta Crystallogr D69:520–533

    Google Scholar 

  158. Economou NJ, Nahoum V, Weeks SD, Gratsky KC, Zentner IJ, Townsend TM, Bhuiya MW, Cocklin S, Loll PJ (2012) A carrier protein strategy yields the structure of dalbavancin. J Am Chem Soc 134:4637–4645

    Article  CAS  Google Scholar 

  159. Muir TW, Sondhi D, Cole PA (1998) Expressed protein ligation: a general method for protein engineering. Proc Natl Acad Sci U S A 95:6705–6710

    Article  CAS  Google Scholar 

  160. Muir TW (2013) Semisynthesis of proteins by expressed protein ligation. Annu Rev Biochem 72:249–289

    Article  CAS  Google Scholar 

  161. Gustafson J, Lim D, Miller SJ (2010) Dynamic kinetic resolution of biaryl atropisomers via peptide-catalyzed asymmetric bromination. Science 328:1251–1255

    Article  CAS  Google Scholar 

  162. Garand E, Kamrath MZ, Jordan PA, Wolk AB, McCoy AB, Miller SJ (2012) Determination of non-covalent docking by IR spectroscopy of cold gas-phase complexes. Science 335:694–698

    Article  CAS  Google Scholar 

  163. Barrett KT, Miller SJ (2013) Enantioselective synthesis of atropisomeric benzamides through peptide-catalyzed bromination. J Am Chem Soc 135:2963–2966

    Article  CAS  Google Scholar 

  164. Barrett KT, Metrano AJ, Rablen PR, Miller SJ (2014) Spontaneous transfer of chirality in an atropisomerically enriched two-axis system. Nature 509:71–75

    Article  CAS  Google Scholar 

  165. Denmark SE, Burk MT (2010) Lewis base catalysis of bromo- and iodolactonization and cycloetherification. Proc Natl Acad Sci U S A 107:20655–20660

    Article  CAS  Google Scholar 

  166. Pathak TP, Miller SJ (2012) Site-selective bromination of vancomycin. J Am Chem Soc 134:6120–6123

    Article  CAS  Google Scholar 

  167. Pathak TP, Miller SJ (2013) Chemical tailoring of teicoplanin with site-selective reactions. J Am Chem Soc 135:8415–8422

    Article  CAS  Google Scholar 

  168. Fu X, Tan CH (2011) Mechanistic considerations of guanidine-catalyzed reactions. Chem Commun 47:8210–8222

    Article  CAS  Google Scholar 

  169. Anderson KW, Buchwald SL (2005) General catalysts for the Suzuki-Miyaura and Songoashira coupling reactions of aryl chlorides and for the coupling of challenging substrate combinations in water. Angew Chem Int Ed 44:6173–6177

    Article  CAS  Google Scholar 

  170. Van Temelen EE, Heys JR (1975) Enzymic epoxidation of squalene variants. J Am Chem Soc 97:1252–1253

    Article  Google Scholar 

  171. Maayan G, Ward MD, Kirshenbaum K (2009) Folded biomimetic oligomers for enantioselective catalysis. Proc Natl Acad Sci U S A 106:13679–13684

    Article  CAS  Google Scholar 

  172. Berkessel A, Koch B, Toniolo C, Rainaldi M, Broxterman QB, Kaptein B (2006) Asymmetric enone epoxidation by short solid-phase bound peptides: further evidence for catalyst helicity and catalytic activity of individual peptide strands. Biopolymers 84:90–96

    Article  CAS  Google Scholar 

  173. Formagio F, Boncio M, Crisma M, Peggion C, Mezzato S, Polese A, Barazza A, Antonello S, Maran F, Broxterman QB, Kaptein B, Kamphuis J, Vitale RM, Saviano M, Benedetti E, Toniolo C (2002) Nitroxyl peptides as catalysts of enantioselective oxidations. Chem Eur J 8:84–93

    Article  Google Scholar 

  174. Peris G, Jakobsche CE, Miller SJ (2007) Aspartate-catalyzed asymmetric epoxidation reactions. J Am Chem Soc 129:8710–8711

    Article  CAS  Google Scholar 

  175. Jakobsche CE, Peris G, Miller SJ (2008) Functional analysis of an aspartate-based epoxidation catalyst with amide-to-alkene peptidomimetic catalyst analogues. Angew Chem Int Ed 120:6809–6813

    Article  Google Scholar 

  176. Kolundzic F, Noshi MN, Tjandra M, Movassaghi M, Miller SJ (2011) Chemoselective and enantioselective oxidation of indoles employing aspartyl peptide catalysts. J Am Chem Soc 133:9104–9111

    Article  CAS  Google Scholar 

  177. Mercado-Marin EV, Garcia-Reynaga P, Romminger S, Pimenta EF, Romney DK, Lodewyk MW, Williams DE, Andersen RJ, Miller SJ, Tantillo DJ, Berlinck RGS, Sarpong R (2014) Total synthesis and isolation of citrinalin and cyclopiamine congeners. Nature 509:293–294

    Article  CAS  Google Scholar 

  178. Gnanadesikan V, Corey EJ (2008) A strategy for position-selective epoxidation of polyprenols. J Am Chem Soc 130:8089–8093

    Article  CAS  Google Scholar 

  179. Chang S, Lee NH, Jacobsen EN (1993) Regio- and enantioselective catalytic epoxidation of conjugated polyenes. Formal synthesis of LTA4 methyl ester. J Org Chem 58:6939–6941

    Article  CAS  Google Scholar 

  180. Burke CP, Shi Y (2006) Regio- and enantioselective epoxidation of dienes by a chiral dioxirane: synthesis of optically active vinyl cis-epoxides. Angew Chem Int Ed 45:4475–4478

    Article  CAS  Google Scholar 

  181. Barlan AU, Baak A, Yamamoto H (2006) Enantioselective oxidation of olefins catalyzed by a chiral bishydroxamic acid complex of molybdenum. Angew Chem Int Ed 45:5849–5852

    Article  CAS  Google Scholar 

  182. Lichtor PA, Miller SJ (2012) Combinatorial evolution of site- and enantioselective catalysts for polyene epoxidation. Nat Chem 4:990–995

    Article  CAS  Google Scholar 

  183. Lichtor PA, Miller SJ (2014) Experimental lineage and functional analysis of a remotely directed peptide epoxidation catalyst. J Am Chem Soc 136:5301–5308

    Article  CAS  Google Scholar 

  184. Abascal NC, Lichtor PA, Giuliano MW, Miller SJ (2014) Function-oriented investigations of a peptide-based catalyst that mediates enantioselective allylic alcohol epoxidation. Chem Sci 5:4504–4511

    Article  CAS  Google Scholar 

  185. Lichtor PA, Miller SJ (2011) One-bead-one-catalyst approach to aspartic acid-based oxidation catalyst discovery. ACS Comb Sci 13:321–326

    Article  CAS  Google Scholar 

  186. Brustad EM, Arnold FH (2011) Optimizing non-natural protein function with directed evolution. Curr Opin Chem Biol 15:201–210

    Article  CAS  Google Scholar 

  187. Foo K, Usui I, Gotz DCG, Werner EW, Holte D, Baran PS (2012) Scalable, enantioselective synthesis of germacrenes and related sesquiterpenes inspired by terpene cyclase phase logic. Angew Chem Int Ed 51:11491–11495

    Article  CAS  Google Scholar 

  188. Yoon TP, Jacobsen EN (2003) Privileged chiral catalysts. Science 299:1691–1693

    Article  CAS  Google Scholar 

  189. Breslow R, Gellman SH (1983) Intramolecular nitrene C-H insertions mediated by transition-metal complexes as nitrogen analogues of cytochrome P-450 reactions. J Am Chem Soc 105:6729–6730

    Article  Google Scholar 

  190. Breslow R, Gellman SH (1982) Tosylamidation of cyclohexane by a cytochrome P-450 model. J Chem Soc Chem Commun 1400–1401

    Google Scholar 

  191. Breslow R (1980) Biomimetic control of chemical selectivity. Acc Chem Res 13:170–177

    Article  CAS  Google Scholar 

  192. Xu D, Crispino GA, Sharpless KB (1992) Selective asymmetric dihydroxylation (AD) of dienes. J Am Chem Soc 114:7570–7571

    Article  CAS  Google Scholar 

  193. Becker H, Soler MA, Sharpless KB (1995) Selective asymmetric dhihydroxylation of polyenes. Tetrahedron 51:1345–1376

    Article  CAS  Google Scholar 

  194. Kolb HC, VanNieuwenhze MS, Sharpless KB (1994) Catalytic asymmetric dihydroxylation. Chem Rev 94:2483–2547

    Article  CAS  Google Scholar 

  195. Jacobsen EN, Pfaltz A, Yamamoto H (eds) (1999) Comprehensive asymmetric catalysis, vol I–III and Supplement 1. Springer, New York

    Google Scholar 

  196. Chen MS, White MC (2007) A predictably selective aliphatic C-H oxidation reaction for complex molecule synthesis. Science 318:783–787

    Article  CAS  Google Scholar 

  197. Newhouse T, Baran PS (2011) If C-H bonds could talk: selective C-H bond oxidation. Angew Chem Int Ed 50:3362–3374

    Article  CAS  Google Scholar 

  198. Vohidov F, Coughlin JM, Ball ZT (2015) Rhodium(II) metallopeptie catalyst design enables fine control in selective functionalization of natural SH3 domains. Angew Chem Int Ed 54:4587–4591

    Article  CAS  Google Scholar 

  199. Ball ZT (2012) Designing enzyme-like catalysts: a rhodium(II) metallopeptide case study. Acc Chem Res 46:560–570

    Article  CAS  Google Scholar 

Download references

Author information

Authors and Affiliations

  1. Department of Chemistry, Yale University, 225 Prospect Street, New Haven, CT, 06520-8107, USA

    Michael W. Giuliano & Scott J. Miller

Authors
  1. Michael W. Giuliano
    View author publications

    You can also search for this author in PubMed Google Scholar

  2. Scott J. Miller
    View author publications

    You can also search for this author in PubMed Google Scholar

Corresponding author

Correspondence to Scott J. Miller .

Editor information

Editors and Affiliations

  1. Institute for Chemical Research Kyoto University, Kyoto, Japan

    Takeo Kawabata

Rights and permissions

Reprints and permissions

Copyright information

© 2015 Springer International Publishing Switzerland

About this chapter

Cite this chapter

Giuliano, M.W., Miller, S.J. (2015). Site-Selective Reactions with Peptide-Based Catalysts. In: Kawabata, T. (eds) Site-Selective Catalysis. Topics in Current Chemistry, vol 372. Springer, Cham. https://doi.org/10.1007/128_2015_653

Download citation

Publish with us

Policies and ethics

Search

Navigation