Flexibility in peptide molecules and restraints imposed by hydrogen bonds, the AIB residue, and core inserts

Abstract

The first segments of this article review some of the early crystal structure determinations of β‐bends, γ‐bends, large conformational changes in cyclic peptides upon complexation with metal ions, and both the stability and drastic change in conformation as a function of the solvent used for growing crystals. More recent structure analyses have concerned helical peptides containing the Aib and/or Dpg residues and associated conformational problems such as 310‐/α‐helix transitions, helix aberrations, reversals, severe curving of the helix, unfolding, and hydration of backbone. Ion channels occurring in three crystal forms of zervamicin and possible ion transport and gating mechanisms are described. Finally, hydrogen bonding patterns are presented in supramolecular assemblies of retropeptides with core inserts consisting of oxalyl, adipoyl, suberoyl and polymethylene moieties. © 1996 John Wiley & Sons, Inc.

Structure-Activity Relation of NH2-terminal Human Parathyroid Hormone Fragments

“…This effect was observed for the COOH-terminal region of the different PTH fragments. Karle and Balaram (51,52) suggest that six-residue sequences are equally likely to form 3 10 -or ␣-helices. Both helices in the hPTH fragments we studied seem to represent an equilibrium between an ␣-helix and 3 10 -helical conformation, the NH 2 -terminal helix having a higher tendency to a more extended 3 10 -helical conformation.…”

Peptides and Peptidomimetics in Medicinal Chemistry

“…The steric bulk of the methyl group reduced the rotational freedom of the two peptide backbone angles and . In the case of Aib, the allowable and backbone angles in peptides are restricted to values near -57°, -47° and +57°, +47° (Karle, 1996).…”

Exploring the conformational space of cyclic peptides by a stochastic search method

“…It may be seen that although the variance in some of the peptides with a similar number of glycines is quite large (when the number of Gly residues is three), the average for two, three, and four Gly residues displays a trend of increasing the number of clusters, while those for Pro display a trend of reduction in the number of clusters. A discussion of the flexibility/rigidity of cyclic peptides [36,66,67] is deferred to another paper in which a detailed analysis and comparison of predicted to reported conformations will be presented.…”