The X‐Pro peptide bond as an nmr probe for conformational studies of flexible linear peptides

The equilibrium between the cis and trans forms of X‐Pro peptide bonds can readily be measured in the 13C nmr spectra. In the present paper we investigate how observation of this equilibrium could be used as an nmr probe for conformational studies of flexible polypeptide chains. The experiments include studies by 13C nmr of a series of linear oligopeptides containing different X‐L‐Pro peptide bonds, with X = Gly, L‐Ala, L‐Leu, L‐Phe, D‐Ala, D‐Leu, and D‐Phe. Overall the study confirms that X‐Pro peptide bonds can generally be useful as 13C nmr probes reporting the formation of nonrandom conformation in flexible polypeptide chains. It was found that the cis–trans equilibrium of X‐Pro is greatly affected by the side chain of X and the configuration of the α‐carbon atom of X. On the basis of these observations some general rules are suggested for a practical applications of the X‐Pro nmr probes in conformational studies of polypeptide chains.

[1]  K. Wüthrich,et al.  Nmr studies of the molecular conformations in the linear oligopeptides H‐(L‐Ala)n‐L‐Pro‐OH , 1976, Biopolymers.

[2]  A. Bellocq,et al.  Conformational analysis by NMR of an analogue of thyrotropin releasing factor: The tripeptide «GLU-LEU-PRO-A , 1975 .

[3]  P. Fromageot,et al.  13C-nuclear magnetic resonance studies of 85% 13C-enriched amino acids and small peptides. pH effects on the chemical shifts, coupling constants, kinetics of cis-trans isomerisation and conformation aspects. , 1975, Biochimica et biophysica acta.

[4]  R. E. Young,et al.  Letter: Long-range steric effects on rotational barriers in peptide chains. , 1975, Biopolymers.

[5]  E. Blout,et al.  A 13C spin‐lattice relaxation study of dipeptides containing glycine and proline: Mobility of the cyclic proline side chain , 1975, Biopolymers.

[6]  D. Rabenstein,et al.  Nuclear magnetic resonance studies of the acid-base chemistry of amino acids and peptides. II. Dependence of the acidity of the C-terminal carboxyl group on the conformation of the C-terminal peptide bond. , 1974, Journal of the American Chemical Society.

[7]  R. Deslauriers,et al.  Conformational mobility of the pyrrolidine ring of proline in peptides and peptide hormones as manifest in carbon 13 spin-lattice relaxation times. , 1974, The Journal of biological chemistry.

[8]  K. Wüthrich,et al.  A novel approach for studies of the molecular conformations in flexible polypeptides , 1974, FEBS letters.

[9]  F. Gurd,et al.  Carbon 13 nuclear magnetic resonance of pentapeptides of glycine containing central residues of methionine, proline, arginine, and lysine. , 1974, The Journal of biological chemistry.

[10]  J. R. Lyerla,et al.  Carbon-13 chemical shifts of amides and imino acid residues. Effects of the carbonyl substituent and syn-anti geometries , 1974 .

[11]  P. Sadler,et al.  13C magnetic resonance study of the ionization of N-acetyl-DL-proline in aqueous solution. , 1974, Biochimica et biophysica acta.

[12]  J. R. Lyerla,et al.  Molecular mobility of polypeptides containing proline as determined by 13C magnetic resonance , 1974, Biopolymers.

[13]  R. Deslauriers,et al.  13C nuclear magnetic resonance studies of the conformation of the X-pro bond in the oligopeptide hormones, thyrotropin-releasing hormone, luteinizing hormone-releasing factor, angiotensin and melanocyte-stimulating hormone release-inhibiting factor. , 1973, Biochemical and biophysical research communications.

[14]  F. Bovey,et al.  Carbon-13 magnetic resonance spectroscopy. Spectrum of proline in oligopeptides , 1973 .

[15]  R. Deslauriers,et al.  Carbon‐13 nuclear magnetic resonance studies on thyrotropin‐releasing factor and related peptides , 1973, FEBS letters.

[16]  K. Wüthrich,et al.  Manifestation in the 13C‐NMR spectra of two different molecular conformations of a cyclic pentapeptide , 1972, FEBS letters.

[17]  R. Deslauriers,et al.  A carbon-13 nuclear magnetic resonance study of oxytocin and its oligopeptides. , 1972, Biochemical and biophysical research communications.

[18]  T. D. Alger,et al.  Nuclear magnetic resonance rate studies of hindered rotation in methyl N-acetylsarcosinate , 1972 .

[19]  D. Patel Proton Nuclear Magnetic Resonance Study of Corticotropins , 1971 .

[20]  D. Patel Proton Nuclear Magnetic Resonance Study of Glucagon , 1970 .

[21]  M. T. Rogers,et al.  cis and trans Configurations of the Peptide Bond in N-Monosubstituted Amides by Nuclear Magnetic Resonance , 1964 .

[22]  Kurt Wüthrich,et al.  NMR in biological research: Peptides and proteins , 1976 .

[23]  W. Voelter,et al.  cis-trans-Isomerie des Thyreotropin-freisetzenden Hormons (TRH) in wäßriger Lösung† , 1974 .

[24]  J. Richards The structure and action of proteins , 1969 .

[25]  G. N. Ramachandran,et al.  Conformation of polypeptides and proteins. , 1968, Advances in protein chemistry.