Bioorganic Chemistry of Amino Acids and Polypeptides

  • Hermann Dugas
Part of the Springer Advanced Texts in Chemistry book series (SATC)


Bioorganic chemistry provides a link between the work of the organic chemist and biochemist, and this chapter is intended to serve as a link between organic chemistry, biochemistry, and protein and medicinal chemistry or pharmacology. The emphasis is chemical and one is continually reminded to compare and contrast biochemical reactions with mechanistic and synthetic counterparts. The organic chemistry of the peptide bond and the phosphate ester linkage (see Chapter 3) are presented “side by side”; this way, a surprising number of similarities are readily seen.


Bioorganic Chemistry Opiate Receptor Optical Purity Catalytic Antibody Peptide Bond Formation 
These keywords were added by machine and not by the authors. This process is experimental and the keywords may be updated as the learning algorithm improves.


Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.


  1. 16.
    R.J.P. Williams (1987), Missing information in bio-inorganic chemistry. Coord. Chem. Rev. 79, 175–193.CrossRefGoogle Scholar
  2. 17.
    G.M. Bodner (1986), Metabolism, parts I, II and III. J. Chem. Educ. 63, 566–570, 673–677, and 772–775.CrossRefGoogle Scholar
  3. 18.
    F. Lipmann (1973), Nonribosomal polypeptide synthesis on polyenzyme templates. Acc. Chem. Res. 6, 361–367.CrossRefGoogle Scholar
  4. 19.
    J.A. Walder, R.Y. Walder, M.J. Heller, S.M. Freier, R.L. Letsinger, and I.M. Klotz (1979), Complementary carrier peptide synthesis: General strategy and implications for prebiotic origin of peptide synthesis. Proc. Nat. Acad. Sci. USA, 76, 51–55.CrossRefGoogle Scholar
  5. 20a.
    D.S. Kemp, D.J. Kerkman, S.L. Leung, and G. Hanson (1981), Intramolecular O,N-acyl transfer via cyclic intermediates of nine and twelve members. Models for extensions of the amine capture strategy for peptide synthesis. J. Org. Chem. 46, 490–498.CrossRefGoogle Scholar
  6. 20b.
    D.S. Kemp and N. Fotouhi (1987), Peptide synthesis by prior thiol capture V. The scope and control of disulfide interchange during the acyl transfer step. Tetrahedron Lett. 28, 4637–4640.CrossRefGoogle Scholar
  7. 21.
    K. Johnsson, R.K. Allemann, H. Widmer, and S.A. Benner (1994), Synthesis, structure and activity of artificial, rationally designed catalytic polypeptides. Nature 365, 530–532.CrossRefGoogle Scholar
  8. 22.
    J.P. Vigneron, H. Kagan, and A. Horeau (1968), Synthèse asmétrique de l’acide aspartique optiquement pur. Tetrahedron Lett. 5681–5683.Google Scholar
  9. 23.
    E.J. Corey, R.J. McCaully, and H.S. Sachdev (1970), Studies on the asymmetric synthesis of a-amino acids. I. A new approach. J. Amer. Chem. Soc. 92, 2476–2488.CrossRefGoogle Scholar
  10. 24.
    M.D. Fryzuk and B. Bosnich (1977), Asymmetric synthesis. Production of optically active amino acids by catalytic hydrogenation. J. Amer. Chem. Soc. 99, 6262–6267.CrossRefGoogle Scholar
  11. 25.
    M.D. Fryzuk and B. Bosnich (1979), Asymmetric synthesis. Preparation of chiral methyl chiral lactic acid by catalytic asymmetric hydrogenation. J. Amer. Chem. Soc. 101, 3043–3049.CrossRefGoogle Scholar
  12. 26.
    N. Takaishi, H. Imai, C.A. Bertelo, and J.K. Stille (1978), Transition metal catalyzed asymmetric organic Synthesis via polymer-attached optically active phosphine ligands. Synthesis of R amino acid and hydratopic acid by hydrogenation. J. Amer. Chem. Soc. 100, 264–267.CrossRefGoogle Scholar
  13. 27.
    M.E. Wilson and G.M. Whitesides (1978), Conversion of a protein to a homogeneous asymmetric hydrogenation catalyst by site-specific modification with a diphosphinerhodium(I) moiety. J. Amer. Chem. Soc. 100, 306–307.CrossRefGoogle Scholar
  14. 28.
    M.E. Wilson, R.G. Nuzzo, and G.M. Whitesides (1978), Bis(2-diphenylphos-phinoethyl)amine. A flexible synthesis of functionalized chelating diphosphines. J. Amer. Chem. Soc. 100, 2269–2270.CrossRefGoogle Scholar
  15. 29.
    W. Marckwald (1904), Veber asymmetrische synthese. Ber. Chem, 37, 1368–1370.CrossRefGoogle Scholar
  16. 30.
    D.A. Evans (1984), Stereoselective alkylation reactions of chiral metal enolates. In: Asymmetric Synthesis (J.D. Morrison, Ed.), Vol. 3. Academic Press, New York.Google Scholar
  17. 31.
    A.I. Meyers, G. Knaus, and K. Kamata (1974), Synthesis via 2-oxazolines. IV. An asymmetric synthesis of 2-methylalkanoic acid from a chiral oxazoline. J. Amer. Chem. Soc. 96, 268–270.CrossRefGoogle Scholar
  18. 32.
    M. Kitamoto, K. Miroi, S. Terashima, and S. Yamada (1974), Stereochemical studies. XXIV. Asymmetric synthesis of 2-alkylcyclohexamines via optically active lithioenamines. Chem. Pharm. Bull. 22, 459–464.Google Scholar
  19. 33.
    T. Katsuki and K.B. Sharpless (1980), The first practical method of asymmetric epoxidation. J. Amer. Chem. Soc. 102, 5974–5976.CrossRefGoogle Scholar
  20. 34.
    D. Seebach, R. Imwinkelried, and T. Weber (1986), in R. Scheffold, Ed., Modern Synthetic Methods. Springer-Verlag, Berlin.Google Scholar
  21. 35.
    D.A. Evans, T.C. Britton, R.L. Dorow, and J.F. Dellaria (1986), Stereoselective aminatin of chiral enolates. A new approach to the asymmetric synthesis of α-amino and derivatives. J. Amer. Chem. Soc. 108, 6395–6397.CrossRefGoogle Scholar
  22. 36.
    F. Schöllkopf and U. Groth (1981), Enantioselective synthesis of (R)-α-vinylamino acids. Angew. Chem. Int. Ed. Engl. 20, 977–978.CrossRefGoogle Scholar
  23. 37.
    M.B. Buergi, J.D. Dunitz, J.-M. Lehn, and G. Wipff (1974), Stereochemistry of reaction paths at carbonyl centres. Tetrahedron 30, 1563–1572.CrossRefGoogle Scholar
  24. 38.
    F.M. Menger (1983), Directionality of organic reactions in solution. Tetrahedron 39, 1013–1040.CrossRefGoogle Scholar
  25. 39.
    J.E. Baldwin (1976), Rules for ring closure. Chem. Commun. 734–736.Google Scholar
  26. 40.
    D.R. Storm and D.E. Koshland, Jr. (1970), A source for the special catalytic power of enzymes: Orbital steering. Proc. Nat. Acad. Sci. USA 66, 445–452.CrossRefGoogle Scholar
  27. 41.
    F.M. Menger and L.E. Glass (1980), Contribution of orbital alignment to organic and enzymatic reactivity. J. Amer. Chem. Soc. 102, 5404–5406.CrossRefGoogle Scholar
  28. 42.
    S. Scheiner, W.N. Lipscomb, and D.A. Kleier (1976), Molecular orbital studies of enzyme activity. 2. Nucleophilic attack and carbonyl systems with comments on orbital steering. J. Amer. Chem. Soc. 98, 4770–4777.CrossRefGoogle Scholar
  29. 43.
    D. Seebach and R. Naef (1981), Enantioselective generation and diastereo-selective reactions of chiral enolates derived from α-hetero-substituted carboxylic acids. Helv. Chim. Acta 64, 2704–2708.CrossRefGoogle Scholar
  30. 44.
    D. Seebach, M. Boes, R. Naef, and W.B. Schweizer (1983), Alkylation of amino acids without loss of the optical activity: Preparation of α-substituted proline derivatives. A case of self-reproduction of chirality. J. Amer. Chem. Soc. 105, 5390–5398.CrossRefGoogle Scholar
  31. 45.
    R.M. Wenger (1985), Synthesis of cyclosporine analogues: Structural requirements for immunosuppressive activity. Angew. Chem. Int. Ed. Engl. 24, 77–85.CrossRefGoogle Scholar
  32. 46.
    D.A. Evans and A.E. Weber (1986), Asymmetric glycine enolate aldol reactions: Synthesis of cyclosporine’s unusual amino acid, MeBmt. J. Amer. Chem. Soc. 108, 6757–6761.CrossRefGoogle Scholar
  33. 47.
    D.A. Evans and T.C. Britton (1987), Electrophilic azide transfer to chiral enolates. A general approach to the asymmetric synthesis of α-amino acids. J. Amer. Chem. Soc. 109, 6881–6883.CrossRefGoogle Scholar
  34. 48.
    G.M. Coppola and M.F. Schuster (1987), Asymmetric Synthesis. J. Wiley & Sons, New York.Google Scholar
  35. 49.
    M.G. Finn and K.B. Sharpless (1985), On the mechanism of asymmetric epoxidation with titanium-tartrate catalysts. In: (J.D. Morrison, Ed.) Asymmetric Synthesis, Vol. 5. Academic Press, Inc., New York.Google Scholar
  36. 50.
    E.N. Jacobsen, I. Markó, W.S. Mungall, G. Schröder, and K.B. Sharpless (1988), Asymmetric dihydroxylation via ligand-accelerated catalysis. J. Amer. Chem. Soc. 110, 1968–1970.CrossRefGoogle Scholar
  37. 51.
    B. Bosnish (1984), Asymmetric Catalysis. Chem. Britain 808–810.Google Scholar
  38. 52.
    H. Brunner (1983), Rhodium catalysts for enantioselective hydrosilylation. A new concept in the development of asymmetric catalyses. Angew. Chem. Int. Ed. Engl. 22, 897–907.CrossRefGoogle Scholar
  39. 53.
    P.A. MacNeil, K.N. Roberts, and B. Bosnish (1981), Asymmetric synthesis. Asymmetric catalytic hydrogenation using chiral chelating six-membered ring bisphosphines. J. Amer. Chem. Soc. 103, 2273–2380.CrossRefGoogle Scholar
  40. 54.
    G.W. Parshall and W.A. Nugent (1988), Making pharmaceuticals via homogeneous catalysis. ChemTech. 184–190.Google Scholar
  41. 55.
    J.W. ApSimon and T. Lee Colhier (1984), Recent Advances in Asymmetric Synthesis II. Tetrahedron 42, 5127–5254.Google Scholar
  42. 56.
    M. Levin-Pinto, J.L. Morgat, P. Fromageot, D. Meyer, J.L. Poulin, and H.B. Kagan (1982), Asymmetric tritiation of N-acetyl dehydro-phenylalanyl(S)-phenylalanine (methyl ester) catalyzed with a rhodium (+)-DIOP complex. Tetrahedron 38, 119–123.CrossRefGoogle Scholar
  43. 57.
    R. Noyori, T. Ohkuma, M. Kitamura, H. Takaya, N. Sayo, H. Kumobayashi, and S. Akutagawa (1987), Asymmetric hydrogénation of β-ketone carboxylic esters. A practical, purely chemical access to β-hydroxy esters in high enantiomeric purity. J. Amer. Chem. Soc. 109, 5856–5857.CrossRefGoogle Scholar
  44. 58.
    T.T. Ngo and G. Tunnicliff (1981), Inhibition of enzymic reactions by transition-state analogs. An approach for drug design. Gen. Pharmac. 12, 129–138.Google Scholar
  45. 59.
    K.T. Douglas (1983), Transition-state analogues in drug design. Chem. & Ind. 311–315.Google Scholar
  46. 60.
    G.M. Blackburn (1981), Phosphonates as analogues of biological phosphates. Chem. & Ind. 134–138.Google Scholar
  47. 61.
    P.A. Bartlett and C.K. Marlowe (1983), Phosphonamidates as transition-state analogue inhibitors of thermolysin. Biochemistry 22, 4618–4624.CrossRefGoogle Scholar
  48. 62.
    N.E. Jacobsen and P.A. Bartlett (1981), A phosphonamidate dipeptide analogue as an inhibitor of carboxypeptidase A. J. Amer. Chem. Soc. 103, 654–657.CrossRefGoogle Scholar
  49. 63.
    P.P. Giannousis and P.A. Bartlett (1987), Phosphorous amino acid analogues as inhibitors of leucine aminopeptidase. J. Med. Chem. 30, 1603–1609.CrossRefGoogle Scholar
  50. 64.
    M.L. Sinnott (1979), Inimitable enzymes? Chem. Britain 15, 293–297.Google Scholar
  51. 65.
    S.D. Copley and J.R. Knowles (1985), The uncatalyzed Claisen rearrangement of chorismate to prephenate prefers a transition-state of chainlike geometry. J. Amer. Chem. Soc. 109, 5306–5308.CrossRefGoogle Scholar
  52. 66.
    S.D. Copley and J.R. Knowles (1987), The conformational equilibrium of chorismate in solution. Implications for the mechanism of the non-enzymic and the enzyme-catalyzed rearrangement of chorismate to prephenate. J. Amer. Chem. Soc. 109, 5008–5013.CrossRefGoogle Scholar
  53. 67.
    P.A. Bartlett and CR. Johnson (1985), An inhibitor of chorismate mutase resembling the transition-state conformation. J. Amer. Chem. Soc. 107, 7792–7793.CrossRefGoogle Scholar
  54. 68.
    J. Jacobs, P.G. Schultz, R. Sugasawara, and M. Powell (1987), Catalytic antibodies. J. Amer. Chem. Soc. 109, 2174–2176.CrossRefGoogle Scholar
  55. 69.
    A. Tramontane, K.D. Janda, and R.A. Lerner (1986), Chemical reactivity at an antibody binding site elicited by mechanistic design of a synthetic antigen. Proc. Natl. Acad. Sci. 83, 6736–6740.CrossRefGoogle Scholar
  56. 70.
    S.J. Pollack, J.W. Jacobs, and P.G. Schultz (1986), Selective chemical catalysis by an antibody. Science 234, 1570–1573.CrossRefGoogle Scholar
  57. 71.
    A.D. Napper, S.J. Benkovic, A. Tramontano, and R.A. Lerner (1987), A stereospecific cyclization catalyzed by an antibody. Science 273, 1041–1043.CrossRefGoogle Scholar
  58. 72.
    V. Morell (1993), Enzyme may blunt cocaine’s action. Science 259, 1828.CrossRefGoogle Scholar
  59. 73.
    R.M. Baum (1993), Antibodies catalyze reactions otherwise difficult to achieve. Chem. & Eng. News, April 19, 33–35.Google Scholar
  60. 74.
    J.-L. Reymond, J.-L. Reber, and R.A. Lerner (1994), Enantioselective, multigram-scale synthesis with a catalytic antibody. Angew. Chem. Int. Ed. Engl. 33, 475–476.CrossRefGoogle Scholar
  61. 75.
    D.A. Campbell, B. Gong, L.M. Kochersperger, S. Yonkovich, M.A. Gallop, and P.G. Schultz (1994), Antibody-catalyzed prodrug activation. J. Amer. Chem. Soc. 116, 2165–2166.CrossRefGoogle Scholar
  62. 76.
    K.E. Neet and D.E. Koshland (1966), The conversion of serine at the active site of subtilisin to cysteine a “chemical mutation.” Proc. Natl. Acad. Sec. USA 56, 1606–1611.CrossRefGoogle Scholar
  63. 77.
    L. Polgar and M.L. Bender (1966), A new enzyme containing a synthetically formed active site. Thiol-subtilisin. J. Amer. Chem. Soc. 88, 3153–3154.CrossRefGoogle Scholar
  64. 78.
    P.I. Clark and G. Lowe (1978), Conversion of the active-site cysteine residue of papain into a dihydro-serine, a serine and a glycine residue. Eur. J. Biochem. 84, 293–299.CrossRefGoogle Scholar
  65. 79.
    J.H. Parish and M.J. McPherson (1987), Chemical and biochemical manipulation of DNA and the expression of foreign genes in micro-organisms. Natural Prod. Rep. 4, 139–156.CrossRefGoogle Scholar
  66. 80.
    M.J. McPherson and J.H. Parish (1987), Applications of recombinant DNA in biotechnology. Natural Prod. Rep. 4, 205–224.CrossRefGoogle Scholar
  67. 81.
    R. Baum (1986), Enzyme research advances protein engineering. Chem. Eng. News, Oct. 13, 23–25.Google Scholar
  68. 82.
    D.S. Lawrence and E.T. Kaiser (1984), Chemical mutation of enzyme active sites. Science 226, 505–511.CrossRefGoogle Scholar
  69. 83.
    J.A. Gerlt (1987), Relationships between enzymatic catalysis and active site structure revealed by applications of site-directed mutagenesis. Chem. Rev. 87, 1079–1105.CrossRefGoogle Scholar
  70. 84.
    J.T. Slama, S.R. Oruganti, and E.T. Kaiser (1981), Semisynthetic enzymes: Synthesis of a new flavopapain with high catalytic efficiency. J. Amer. Chem. Soc. 103, 6211–6213.CrossRefGoogle Scholar
  71. 85.
    H. Zemel (1987), A new semisynthetic esterase. J. Amer. Chem. Soc. 109, 1875–1876.CrossRefGoogle Scholar
  72. 86.
    G. Henderson and I. McFedzean (1985), Opioids—a review of recent developments. Chem. Britain 1094–1097.Google Scholar
  73. 87.
    G.J. Hite (1981), In: Principles of medicinal chemistry (W.O. Foye, Ed.), Chap. 12. Lea & Febiger, USA.Google Scholar
  74. 88.
    B. Belleau (1982), Stereoelectronic regulation of the opiate receptor. Some conceptual problems. In: Chemical Regulation of Biological Mechanisms. Burlington House, London.Google Scholar
  75. 89.
    J. Hughes, T.W. Smith, H.N. Kosterlitz, L.A. Forthergill, and B.A. Morgan (1975), Identification of two related pentapeptides from the brain with potent opiate agonist activity. Nature 258, 577–579.CrossRefGoogle Scholar
  76. 90.
    B.P. Roques, C. Garbay-Jaureguiberry, R. Oberlin, M. Anteunis, and A.K. Lala (1976), Conformation of Met5-enkephalin determined by high field PMR spectroscopy. Nature 262, 778–779.CrossRefGoogle Scholar
  77. 91.
    C. Garbay-Jaureguiberry, D. Marion, E. Fellion, and B.P. Roques (1982), Refinement of conformational frequencies of Leu enkephalin and Tyr-Gly-Phe by 15N-NMR. Int. J. Pet Protein Res. 20, 443–450.CrossRefGoogle Scholar
  78. 92.
    I.L. Karle, J. Karle, D. Mastropaolo, A. Camerman, and N. Camerman (1983), [Leu5]enkephalin: Four cocrystallizing conformers with extended backbones that form an antiparallel β-sheet. Acta Crystallogr. Sect. B 39, 625–637.CrossRefGoogle Scholar
  79. 93.
    H. Dugas, P. Mayers, and P. Couillard (1994), A molecular modeling study of the direct effect of Leu-enkephalin on Amoeba proteus membrane in the presence of ions. Endocrine 2, 651–658.Google Scholar
  80. 94.
    P.W. Schiller and J. Di Maio (1982), Opiate receptor subclasses differ in their conformational requirments. Nature 297, 74–76.CrossRefGoogle Scholar
  81. 95.
    P.W. Schiller (1986). In: R.S. Rapaka, G. Barnett, and R.L. Hawks, Eds., Opioid Peptides: Medicinal Chemistry, pp. 291–311, UIDA Research Monograph 69.Google Scholar
  82. 96.
    P.S. Portoghese, D.L. Larson, G. Ronsisvalle, P.W. Schiller, T.M.D. Nguyen, C. Lemieux, and A.E. Takemori (1987), Hybrid bivalent ligands with opiate and enkephalin pharmacophores. J. Med. Chem. 30, 1991–1994.CrossRefGoogle Scholar

Copyright information

© Springer-Verlag New York, Inc. 1996

Authors and Affiliations

  • Hermann Dugas
    • 1
  1. 1.Département de ChimieUniversité de MontréalMontréalCanada

Personalised recommendations