Unconstrained Homooligomeric γ-Peptides Show High Propensity for C₁₄ Helix Formation

Abstract

Monosubstituted γ(4)-residues (γ(4)Leu, γ(4)Ile, and γ(4)Val) form helices even in short homooligomeric sequences. C14 helix formation is established by X-ray diffraction in homooligomeric (γ)n tetra-, hexa- and decapeptide sequences demonstrating the high propensity of γ residues, with proteinogenic side chains, to adopt locally folded conformations.

Conformational properties and aggregation of homo‐oligomeric β3(R)‐valine peptides in organic solvents

“…Backbone conformational flexibilities may be restricted by multiple substitutions or by the use of cyclization restricting backbone CC torsion angles . As part of a program to investigate the intrinsic conformational preferences of β‐ and γ‐ residues derived by backbone homologation of genetically coded α amino acids (proteinogenic residues), we have been examining the solution conformations of homo‐oligomeric sequences of monosubstituted β 3 and γ 4 amino acids . In a recent report we investigated the conformation of a 9‐residue β 3 ( R )Val homo‐oligomer.…”

“…[6] As part of a program to investigate the intrinsic conformational preferences of band gresidues derived by backbone homologation of genetically coded a amino acids (proteinogenic residues), we have been examining the solution conformations of homo-oligomeric sequences of monosubstituted b 3 and g 4 amino acids. [12][13][14] In a recent report we investigated the conformation of a 9-residue b 3 (R) Val homo-oligomer. While the peptide existed predominantly in an aggregated form in CDCl 3 solution, addition of small amounts of the polar, hydrogen bonding solvent DMSO resulted in disaggregation, permitting complete 1 H NMR assignments and establishment of a 14-helical conformation at a solvent composition of 45% (v/v, DMSO:CDCl 3 ).…”

Homooligomeric β3(R)‐valine peptides: Transformation between C14 and C12 helical structures induced by a guest Aib residue

“…Oligo α ‐Val sequences are highly insoluble in solvents like CHCl 3 at lengths 4–9 residues . The corresponding γ 4 ‐Val sequences are highly soluble and have been shown to fold into C 14 ‐helices, which are backbone expanded analogues of the α ‐peptide 3 10 (C 10 ) helix and the β‐peptide C 12 ‐helix. In sharp contrast to the γ 4 homologs, homooligomeric β 3 ‐peptides show limited solubility at the tetra to hexapeptide level in CHCl 3 but lengthening to the 9‐residue sequence enhanced solubility and facilitated formation of β ‐peptide C 14 ‐helices, with the reverse hydrogen bond directionality.…”

“…Recent work from our laboratory has shown that homooligomeric sequence of γ 4 ‐valine have a pronounced tendency to fold into γ peptide C 14 ‐helices, which are backbone expanded analogues of the α ‐peptide 3 10 ‐helix and the β‐peptide 12‐helix . In this study, we examine the conformational possibilities of homooligomeric β 3 ‐peptides and explore the effect of inserting a single guest Aib residue into an oligo β 3 ( R )Val sequence (Figure ).…”

C9/12 Ribbon‐Like Structures in Hybrid Peptides Alternating α‐ and Thiazole‐Based γ‐Amino Acids

“…[1] Initial works focusedo np seudopeptideo ligomers [2] that comprised of as ingle type of monomer subunit,m ainly b-, g-, or d-aminoa cids, [3] and on backbones closely related to peptides,s uch as peptoids or oligoureas. [1] Initial works focusedo np seudopeptideo ligomers [2] that comprised of as ingle type of monomer subunit,m ainly b-, g-, or d-aminoa cids, [3] and on backbones closely related to peptides,s uch as peptoids or oligoureas.…”