Helices and other secondary structures of β‐ and γ‐peptides

Abstract

The principal secondary structural motifs adopted by peptides assembled from beta-amino acid units are discussed: the 14-, 12-, 10-, 12/10-, and 8-helices, as well as the hairpin turn, extended structures, stacks, and sheets. Features that promote a particular folding propensity are outlined and illustrated by structures determined in solution (NMR) and in the solid-state (x-ray). The N-C(beta)-C(alpha)-CO dihedral angles from molecular dynamics simulations, which are indicative of a particular secondary structure, are presented. A brief description of a helix and a turn of gamma-peptides is also given.

Downsizing human, bacterial, and viral proteins to short water-stable alpha helices that maintain biological potency

“…The 116 residue HIV-Rev protein binds to RNA with Kd approximately 1 nM (28). Nociceptin (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17) is an agonist at only nM concentrations (25). We also found the helix-constrained compounds to be more stable in human serum than their linear analogues, the latter being typically degraded within 1 h whereas the constrained peptides were stable for >24 h, except for the exocyclic residues, which were cleaved by proteases over several hours.…”

“…1B and Table S5). This exceptional structural and chemical stability, achieved without incorporating any unnatural components, offers significant advantages over other methods being trialled for protein helix mimicry (5)(6)(7)(8)(9)(10).…”

“…This relatively low helicity for mimetic 26 versus mimetics 20, 22, and 24 is attributed to the unstructured "triggering" message domain at the N-terminus, as well as accumulation of positive charges on one helix face. Nevertheless, the induction of at least some helix structure in this peptide suggested that it should be more active than nociceptin (1)(2)(3)(4)(5)(6)(7)(8)(9)(10)(11)(12)(13)(14)(15)(16)(17). Function was investigated by nociceptin(1-17) induced intracellular ERK phosphorylation in mouse Neuro-2a neuroblastoma cells (Fig.…”

“…However, short synthetic peptides of this length are usually not thermodynamically stable helices in water and adopt only random structures (4). Techniques developed as generalized strategies for stabilising or mimicking short peptide α-helices have been limited by lack of helical structure in water, by sequence or context dependent helicity, by low biological potency or by poor target specificity (5)(6)(7)(8)(9)(10). Either these techniques have failed to induce α-helicity through an entire peptide, had complex synthetic routes that limited broad utility, or have not been applicable across a wide range of biological sequences and receptor types.…”

Co-assembly of helical β3-peptides: a self-assembled analogue of a statistical copolymer

“…Peptides made entirely from "unnatural" β 3 amino acids offer stability and versatility far surpassing α-peptides [13,14]. As opposed to the "binary" α-helix and β-sheet conformations of natural oligopeptides, β-peptides exhibit a range of -mostly helicalsecondary structures [15]. Of particular interest are β 3 -peptides that fold into helices consisting 14-membered loops through hydrogen bonding between C=O of residues i and the N-H of the i-3 residue [16,17].…”