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Chiral, fully extended helical peptides

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Abstract

The synthesis of the N-protected (blocked) homo-peptide esters from the chiral Cα-ethyl, Cα-n-pentylglycine was performed in solution to the hexapeptide level. The conformational propensity exhibited by these oligomers in chloroform solution and in the crystal state was assessed by use of FTIR absorption, NMR, and X-ray diffraction. The results indicated that fully extended helical structures (2.05-helices) are overwhelmingly adopted irrespective of the peptide main-chain length. This oligomeric series is of great interest as it is characterized by the longest C α i ,…, C α i+1 (per residue) separation achievable in the class of chiral, rigid, helical peptide spacers based on α-amino acids.

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Abbreviations

Ac:

Acetyl

Ac n c:

1-Aminocycloalkane-1-carboxylic acid

Aib:

α-Aminoisobutyric acid or Cα-methylalanine or Cα,α-dimethylglycine

(αMe)AA:

Cα-Methylated α-amino acid

Beg:

Cα-n-Butyl, Cα- ethylglycine

Deg:

Cα,α-Diethylglycine

DMAP:

4-(dimethylamino)Pyridine

DMSO:

Dimethylsulphoxide

Dpg:

Cα,α-di-n-Propylglycine

EDC:

N-Ethyl,N′-[3-(dimethylamino)propyl]carbodiimide

Epg:

Cα-Ethyl, Cα-n-pentylglycine

Etn:

Cα-Ethylnorvaline or Cα-ethyl, Cα-n-propylglycine

EtOH:

Ethanol

Iva:

Isovaline or Cα-methyl, Cα-ethylglycine

MeOH:

Methanol

MTBE:

Methyl, tert-butyl ether

OMe:

Methoxy

OSu:

Succinimido

OtBu:

tert-Butoxy

TEMPO:

2,2,6,6-Tetramethylpiperidinyl-1-oxy

Tfa:

Trifluoroacetyl

Z:

Benzyloxycarbonyl

References

  • Åberg A, Yaremchuk A, Tukalo M, Rasmussen B, Cusack S (1977) Crystal structure analysis of the activation of histidine in Thermus thermophilus histidyl-tRNA synthetase. Biochemistry 36:3084–3094

    Article  Google Scholar 

  • Benedetti E, Barone V, Bavoso A, Di Blasio B, Lelj F, Pavone V, Pedone C, Bonora GM, Toniolo C, Leplawy MT, Kaczmarek K, Redlinski A (1988) Structural versatility of peptides from Cα,α-dialkylated glycines. I. A conformational energy computation and X-ray diffraction study of homo-peptides from Cα,α-diethylglycine. Biopolymers 27:357–371

    Article  CAS  Google Scholar 

  • Benedetti E, Di Blasio B, Pavone V, Pedone C, Toniolo C, Crisma M (2002) Characterization at atomic resolution of peptide helical structures. Biopolymers 32:453–456

    Article  Google Scholar 

  • Beychock S (1967) Circular dichroism of poly-α-amino acids and proteins. In: Fasman GD (ed) Poly-α-amino acids: protein models for conformational studies. Dekker, New York, NY, pp 293–337

    Google Scholar 

  • Birkedal H, Schwarzenbach D, Pattison P (2002) A fully extended tetrapeptide consisting of natural amino acids. Chem Commun, pp 2812–2813

  • Brückner H, Kirschbaum J (2010) Sequences of the polypeptide antibiotics (peptaibiotics) acretocins. In: Lebl M, Meldal M, Jensen KJ, Hoeg-Jensen T (eds) Peptides 2010: tales of peptides, the proceedings of the 31st European peptide symposium, European Peptide Society, pp 386–387

  • Carpino LA, Sadat-Aalae D, Chao HG, DeSelms RH (1990) ((9)-Fluorenylmethyl)oxy)carbonyl (FMOC) amino acid fluorides. Convenient new peptide coupling reagents applicable to the FMOC/tert-butyl strategy for solution and solid-phase syntheses. J Am Chem Soc 112:9651–9652

    Article  CAS  Google Scholar 

  • Chen CS, Fujimoto Y, Girdaukas G, Sih CJ (1982) Quantitative analyses of biochemical kinetic resolutions of enantiomers. J Am Chem Soc 104:7294–7299

    Article  CAS  Google Scholar 

  • Cung MT, Marraud M, Néel J (1972) Étude expérimentale de la conformation de molécules dipeptidiques Comparaison avec les prévisions théoriques. Ann Chim (Paris) 7:183–209

    CAS  Google Scholar 

  • De Zotti M, Schievano E, Mammi S, Kaptein B, Broxterman QB, Singh SB, Brückner H, Toniolo C (2010) Configurational assignment of d- and l-isovalines in intact, natural, and synthetic peptides by 2D-NMR spectroscopy. Chem Biodivers 7:1612–1624

    Article  PubMed  Google Scholar 

  • Duchateau ALL, Knuts H, Boesten JMM, Guns JJ (1992) Enantioseparation of amino compounds by derivatization with o-phthaldialdehyde and d-3-mercapto-2-methylpropionic acid. J Chromatogr 623:237–245

    Article  CAS  Google Scholar 

  • Fredenhagen A, Molleyres L-P, Böhlendorf B, Laue G (2006) Structure determination of neoefrapeptins A to N: peptides with insecticidal activity produced by the fungus Geotrichum candidum. J Antibiot 59:267–280

    Article  PubMed  CAS  Google Scholar 

  • Hovmöller S, Zhou T, Ohlson T (2002) Conformation of amino acids in proteins. Acta Crystallogr 58D:768–776

    Google Scholar 

  • Imawaka N, Tanaka M, Suemune H (2000) The first fully planar C5 conformation of homooligopeptides prepared from a chiral α-ethylated α,α-disubstituted amino acid: (S)-butylethylglycine (=(2S)-2-amino-2-ethylhexanoic acid). Helv Chim Acta 83:2823–2835

    Article  CAS  Google Scholar 

  • Karle IL, Balaram P (1990) Structural characteristics of α-helical peptide molecules containing Aib residues. Biochemistry 29:6747–6756

    Article  PubMed  CAS  Google Scholar 

  • Kennedy DF, Crisma M, Toniolo C, Chapman D (1991) Studies of peptides forming 310- and α-helices and β-bend ribbon structures in organic solutions and in model membranes by Fourier transform infrared spectroscopy. Biochemistry 30:6541–6548

    Article  PubMed  CAS  Google Scholar 

  • Kopple KD, Schamper TJ (1972) Proton magnetic resonance line broadening produced by association with a nitroxide radical in studies of amide and peptide conformation. J Am Chem Soc 94:3644–3646

    Article  PubMed  CAS  Google Scholar 

  • Kopple KD, Ohnishi M, Go A (1969) Conformations of cyclic peptides III. Cyclopentaglycyltyrosyl and related compounds. J Am Chem Soc 91:4264–4272

    Article  CAS  Google Scholar 

  • Kubelka J, Keiderling TA (2001) Differentiation of β-sheet forming structures: Ab initio-based simulations of IR absorption and vibrational CD for model peptide and protein β-sheets. J Am Chem Soc 123:12048–12058

    Article  PubMed  CAS  Google Scholar 

  • Kubelka J, Kim J, Bour C, Keiderling TA (2006) Contribution of transition dipole coupling to amide coupling in IR spectra of peptide secondary structures. Vib Spectrosc 42:63–73

    Article  CAS  Google Scholar 

  • Maekawa H, Ballano G, Toniolo C, Ge N-H (2011) Linear and two-dimensional infrared spectroscopic study of the amide I and II modes in fully extended peptide chains. J Phys Chem B. doi:10.1021/jp105527n (in press)

  • Martin D, Hauthal HG (1975) Dimethyl sulphoxide. Van Nostrand-Reinhold, Wokingham, UK

    Google Scholar 

  • Miyazawa T (1967) Infrared spectra and helical conformations. In: Fasman GD (ed) Poly-α-amino acids: protein models for conformational studies. Dekker, New York, NY, pp 69–103

    Google Scholar 

  • Paquet A (1982) Introduction of 9-fluorenylmethoxycarbonyl, trichloroethoxycarbonyl, and butyloxycarbonyl amine protecting groups into O-unprotected hydroxyamino acids using succinimidyl carbonates. Can J Chem 60:976–979

    Article  CAS  Google Scholar 

  • Pauling L, Corey RB (1951) Conformations of polypeptide chains with favored orientations around single bonds: two new planar sheets. Proc Natl Acad Sci USA 37:729–740

    Article  PubMed  CAS  Google Scholar 

  • Pysh ES, Toniolo C (1977) Conformational analysis of protected norvaline oligopeptides by high resolution proton nuclear magnetic resonance. J Am Chem Soc 99:6211–6219

    Article  PubMed  CAS  Google Scholar 

  • Rainaldi M, Moretto A, Peggion C, Formaggio F, Mammi S, Peggion E, Galvez JA, Diaz-de-Villegas MD, Cativiela C, Toniolo C (2003) Lipopeptaibol metabolites of Tolypocladium geodes: total synthesis, preferred conformation, and membrane activity. Chem Eur J 9:3567–3576

    Article  CAS  Google Scholar 

  • Scriven EFV (1983) 4-Dialkylaminopyridines: super acylation and alkylation catalysts. Chem Soc Rev 12:129–161

    Article  CAS  Google Scholar 

  • Sheldrick GM (2008) A short history of SHELX. Acta Crystallogr 64A:112–122

    Google Scholar 

  • Sonke T, Kaptein B, Boesten WHJ, Broxterman QB, Schoemaker HE, Kamphuis J, Formaggio F, Toniolo C, Rutjes FPJT (2000) Aminoamidase-catalyzed preparation and further transformations of enantiopure α-hydrogen and α,α-disubstituted α-amino acids. In: Patel NK (ed) Stereoselective biocatalysis. Dekker, New York, NY, pp 23–58

    Google Scholar 

  • Sonke T, Ernste S, Tandler RF, Kaptein B, Peeters WPH, van Assema FBJ, Wubbolts MG, Schoemaker HE (2005) l-Selective amidase with extremely broad substrate specificity from Ochrobactrum anthropi NCIMB 40321. Appl Environ Microbiol 71:7961–7973

    Article  PubMed  CAS  Google Scholar 

  • Tanaka M (2007) Design and synthesis of chiral α,α-disubstituted amino acids and conformational study of their oligopeptides. Chem Pharm Bull 55:349–358

    Article  PubMed  CAS  Google Scholar 

  • Toniolo C (1980) Intramolecularly hydrogen-bonded peptide conformations. CRC Crit Rev Biochem 9:1–44

    Article  PubMed  CAS  Google Scholar 

  • Toniolo C (1993) Cα,α-Symmetrically disubstituted glycines: useful building blocks in the design of conformationally restricted peptides. Janssen Chim Acta 11:10–16

    CAS  Google Scholar 

  • Toniolo C, Benedetti E (1991a) The polypeptide 310-helix. Trends Biochem Sci 16:350–353

    Article  PubMed  CAS  Google Scholar 

  • Toniolo C, Benedetti E (1991b) Structures of polypeptides from α-amino acids disubstituted at the α-carbon. Macromolecules 24:4004–4009

    Article  CAS  Google Scholar 

  • Toniolo C, Benedetti E (1991c) The fully extended polypeptide conformation. In: Balaram P, Ramaseshan S (eds) Molecular conformations and biological interactions. Indian Academy of Sciences, Bangalore, India, pp 511–521

  • Toniolo C, Brückner H (2009) Peptaibiotics: fungal peptides containing α-dialkyl α-amino acids. Wiley-VCH, Weinheim, Germany

    Google Scholar 

  • Toniolo C, Bonora GM, Bavoso A, Benedetti E, Di Blasio B, Pavone V, Pedone C, Barone V, Lelj F, Leplawy MT, Kaczmarek K, Redlinski A (1988) Structural versatility of peptides from Cα,α-dialkylated glycines. II. An IR absorption and 1H NMR study homo-oligopeptides from Cα,α-diethylglycine. Biopolymers 27:373–379

    Article  CAS  Google Scholar 

  • Toniolo C, Crisma M, Formaggio F, Peggion C (2001) Control of peptide conformation by the Thorpe–Ingold effect (Cα-tetrasubstitution). Biopolymers (Pept Sci) 60:396–419

    Article  CAS  Google Scholar 

  • Toniolo C, Crisma M, Formaggio F, Peggion C, Broxterman QB, Kaptein B (2004) Molecular spacers for physicochemical investigations based on novel helical and extended peptide structures. Biopolymers (Pept Sci) 76:162–176

    Article  CAS  Google Scholar 

  • Toniolo C, Crisma M, Formaggio F, Moretto A, Peggion C, Kaptein B, Broxterman QB (2009) Spectroscopic characterization of the fully-extended, peptide 2.05-helix based on chiral, Cα-ethylated α-amino acids. In: Del Valle S, Escher E, Lubell WD (eds) Peptides for youth: the proceedings of the 20th American peptide symposium. Springer Science, New York, NY, pp 45–46

  • Touw WG, Vriend G (2010) On the complexity of the Engh and Huber refinement restraints: the angle τ as example. Acta Crystallogr D 66:1341–1350

    Article  PubMed  Google Scholar 

  • Tsantrizos YS, Pischos S, Sauriol F (1996) Structural assignment of the peptide antibiotic LP 237–F8, a metabolite of Tolypocladium geodes. J Org Chem 61:2118–2121

    Article  CAS  Google Scholar 

  • Valle G, Crisma M, Toniolo C, Holt EM, Tamura M, Bland J, Stammer CH (1989a) Crystallographic characterization of conformation of 1-aminocyclopropane-1-carboxylic acid residue (Ac3c) in simple derivatives and peptides. Int J Pept Protein Res 34:56–65

    Article  PubMed  CAS  Google Scholar 

  • Valle G, Crisma M, Toniolo C, Beisswenger R, Rieker A, Jung G (1989b) First observation of a helical peptide containing a chiral residue without a preferred screw sense. J Am Chem Soc 111:6828–6833

    Article  CAS  Google Scholar 

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Acknowledgments

A.M. and F.F. are grateful to the University of Padova for financial support through the PRAT 2007 funding initiative.

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Authors and Affiliations

  1. ICB, Padova Unit, CNR, Department of Chemistry, University of Padova, via Marzolo 1, 35131, Padua, Italy

    Marco Crisma, Alessandro Moretto, Cristina Peggion, Fernando Formaggio & Claudio Toniolo

  2. DSM Innovative Synthesis BV, P.O. Box 18, 6160 MD, Geleen, The Netherlands

    Lavinia Panella, Bernard Kaptein & Quirinus B. Broxterman

Authors
  1. Marco Crisma
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  2. Alessandro Moretto
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  3. Cristina Peggion
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  4. Lavinia Panella
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  6. Quirinus B. Broxterman
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  7. Fernando Formaggio
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  8. Claudio Toniolo
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Correspondence to Claudio Toniolo.

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Crisma, M., Moretto, A., Peggion, C. et al. Chiral, fully extended helical peptides. Amino Acids 41, 629–641 (2011). https://doi.org/10.1007/s00726-011-0839-9

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