Single and multiple peptide γ-turns: literature survey and recent progress

Abstract

In contrast to the extensively investigated b-turn conformation in peptides and proteins, single and multiple g-turns have been much less commonly studied. Single and non-contiguous multiple g-turns have been relatively often authenticated in small cyclic peptides, but these important peptide mainchain reversal motifs have not been examined carefully either in linear peptides or in globular proteins.This Perspective article summarizes literature data on this aspect of peptide stereochemistry, expanding the discussion also to the rarely found, contiguous multiple g-turns which generate incipient or fullydeveloped 2.2 7 -(g-) helices. Unpublished results of recent research activities on this topic ongoing in our laboratories are also briefly outlined.L-amino acids are labeled. In C, a g-turn enclosed into a larger e-turn (C 11 form) is illustrated.

Synthesis and Conformational Study of Monosubstituted Aminoferrocene‐Based Peptides Bearing Homo‐ and Heterochiral Pro‐Ala Sequences

“…Although β‐turns are preferred over γ‐turns, the latter are also abundant in crystallized proteins, in which they can be stabilized by long‐range interactions, or even in some types of short linear peptides, in which they are induced by intramolecular hydrogen bonds , , . A literature survey of relatively scarce γ‐turns has been published recently . A few examples confirmed the existence of consecutive γ‐turn conformations in linear peptides.…”

“…Some recent reports pointed to the possibility that heterochiral sequences might adopt γ‐turns in crystal structures, although they are much less frequent than β‐turns. This happens especially in the absence of competing intermolecular hydrogen bonds, either with solvents or with other peptide molecules , . Likewise, an experimental study of small model peptides in solution, namely, t BuCO–Pro–X aa –NHCH 3 with various amino acids X aa , confirmed the competition between ten‐ and seven‐membered rings in alanine‐containing compounds …”

Helically Chiral Peptides That Contain Ferrocene‐1,1′‐diamine Scaffolds as a Turn Inducer

“…NaN 3 ,L iOH, [D 6 ]DMSO (Sigma-Aldrich); HOBt, HBTU, EDC·HCl, BocÀl-AlaÀOH, BocÀd-AlaÀOH, HÀl-ProÀOH and HÀd-ProÀOH (Advanced ChemTech);S OCl 2 (Alfa Aesar) and 2picolinic acid (Sigma-Aldrich) were used as received (compounds 18-26). BocÀAlaÀOH was activated by coupling reagents HBTU/HOBt for 2h in CH 2 Cl 2 and then coupled to ProÀOMe, after which, the resulting product BocÀAlaÀProÀ OMe was hydrolyzed by using LiOH (compounds [18][19][20][21][22][23][24][25][26]. The syntheses of BocÀProÀNHÀFnÀCOOMe (1) had been previously described.…”

“…[26] As the observed resonances of NH Fn groups are notably shifted downfield (d 0 9.2 ppm), their participation in hydrogen bonding is strongly supported ( Table 3) and corroborated by DFT studies, because all the predicted conformers (A-D,F igure 7) have NH Fn groups engaged in seven-, ten-,o rt hirteen-membered hydrogen-bondedr ings. [8d] Although each of the symmetrically disubstituted peptides (16,17,(21)(22)(23)(24)c ontains four NH groups,o nly two kinds of NH resonances were observed at d % 9( NH Fn )a nd % 5-6.5 ppm (AlaÀNH Boc/Ac ), which indicates conformationsi n which both dipeptide chains attached at NH Fn are accommodated into identical environments. The pronouncedu pfield shift of AlaÀNH Boc protons (d = 5.18-5.41 ppm) is influenced by the chemically distinct character of the urethane moiety in the Boc-protected N-terminus residues, and therefore, does not exclude their possible hydrogen-bond engagement.…”

Intramolecular backbone···backbone hydrogen bonds in polypeptide conformations. The other way around: ɛ‐turn

“…An intramolecular H‐bond between the m th N‐H of an α‐amino acid sequence and the n th C = O is designated as m → n (H‐bonding donor → H‐bonding acceptor). As a consequence, the possible intramolecularly H‐bonded sets of 3D structures in a system of four covalently linked peptide units (Figure ) include ( A ): the 3 → 1 (or 4 → 2, or 5 → 3, or C 7 ‐, or γ‐turn); the 4 → 1 (or 5 → 2, or C 10 ‐, or β‐turn); and the 5 → 1 (or C 13 ‐, or α‐turn) conformations. ( B ): the 2 → 2 (or 3 → 3, or 4 → 4, or C 5 , or fully extended); the 2 → 3 (or 3 → 4, or C 8 ‐, or δ‐turn); the 2 → 4 (or C 11 ‐, or ɛ‐turn) conformations.…”