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Solvent and side‐chain contributions to the two‐ cis ⇄ all‐ trans equilibria of cyclic hexapeptides, cyclo ( Xxx ‐Pro‐ D ‐ Yyy ) 2
Author(s) -
Kopple Kenneth D.,
Sarkar Susanta K.,
Giacometti Giovanni
Publication year - 1981
Publication title -
biopolymers
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.556
H-Index - 125
eISSN - 1097-0282
pISSN - 0006-3525
DOI - 10.1002/bip.1981.360200614
Subject(s) - chemistry , solvation , intramolecular force , side chain , solvent , methylene , hydrogen bond , stereochemistry , peptide , crystallography , peptide bond , molecule , medicinal chemistry , organic chemistry , polymer , biochemistry
Cyclic hexapeptides of the type cyclo ( L ‐ Xxx ‐ L ‐Pro‐ D ‐ Yyy ) 2 or cyclo ( L ‐ Xxx ‐ L ‐Pro‐Gly) 2 exist in solution predominantly in two forms of C 2 average symmetry, one with all‐ trans peptide bonds and generally well‐established conformation, and another with both Xxx ‐Pro peptide bonds cis . We have been measuring the thermodynamic parameters of this equilibrium using carbon and proton nmr spectroscopy. Data have been obtained for peptides in which Yyy = Gly, D ‐Ala, or D ‐Phe, and Xxx = Gly, L ‐Ala, L ‐Leu, and L ‐Val. In a given solvent, stability of the all‐ trans form decreases (ΔG 0 increases) as Xxx is changed through the series Gly, L ‐Ala‐, L ‐Leu, and L ‐Val, consistent with expected increasing repulsion between the Xxx side chain and the proline δ methylene across the trnas Xxx ‐Pro bond. Also, for a given set of side chains, the stability of the all‐ trnas form increases as the polarity of the solvent decreases, consistent with models in which all CO and NH groups are accessible for solvation in the two‐ cis form, but two CO and two NH groups are somewhat sequestered in the all‐ trans form. With the available data it is not possible to identify pure intramolecular (solvent‐independent) or pure peptide‐bond solvation (side chain‐independent) terms in Δ H ° or Δ S °, although trends are discernible.