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Studies on intramolecular hydrogen bonding between the pyridine nitrogen and the amide hydrogen of the peptide: synthesis and conformational analysis of tripeptides containing novel amino acids with a pyridine ring
Author(s) -
Hanyu Masayuki,
Ninomiya Daisuke,
Yanagihara Ryoji,
Murashima Takashi,
Miyazawa Toshifumi,
Yamada Takashi
Publication year - 2005
Publication title -
journal of peptide science
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.475
H-Index - 66
eISSN - 1099-1387
pISSN - 1075-2617
DOI - 10.1002/psc.647
Subject(s) - tripeptide , chemistry , intramolecular force , pyridine , hydrogen bond , stereochemistry , amide , peptide bond , peptide , amino acid , glycine , dipeptide , ring (chemistry) , medicinal chemistry , molecule , organic chemistry , biochemistry
For the first time tripeptides, Z‐AA 1 ‐Xaa‐AA 3 ‐OMe (AA 1 and AA 3 = Gly or Aib, Xaa = 2Pmg and 2Pyg) were prepared containing α‐methyl‐α‐(2‐pyridyl)glycine (2Pmg) and α‐(2‐pyridyl)glycine (2Pyg) by solid‐phase Ugi reaction. These results clearly indicate that for the preparation of tripeptides containing an amino acid with a pyridine ring, the solid‐phase Ugi reaction is very useful. NMR analysis clarified that 2Pmg‐containing tripeptides adopt a unique conformation with an intramolecular hydrogen bond between 2Pmg‐NH and the pyridine nitrogen. However, in the case of Z‐Gly‐2Pyg‐Gly‐OMe, the intramolecular hydrogen bonding between 2Pyg‐NH and the pyridine nitrogen was not observed, whereas Z‐Aib‐2Pyg‐Aib‐OMe adopts a unique conformation with an intramolecular hydrogen bond between 2Pyg‐NH and a pyridine nitrogen. Conformational analysis of the tripeptides, Z‐AA 1 ‐Xaa‐AA 3 ‐OMe (AA 1 , AA 3 = Gly or Aib, Xaa = α,α‐di(2‐pyridyl)glycine (2Dpy), α‐phenyl‐α‐(2‐pyridyl)glycine (2Ppg), 2Pmg and 2Pyg), clarified that when an α,α‐disubstituted glycine with a 2‐pyridyl group at an α‐carbon atom is introduced into any peptide, an intramolecular hydrogen bond between a pyridine nitrogen and an amide proton is formed and conformational mobility of the peptide backbone is restricted. Copyright © 2005 European Peptide Society and John Wiley & Sons, Ltd.