Helix-loop-helix peptide foldamers and their use in the construction of hydrolase mimetics

Interplay of secondary and tertiary folding in abiotic foldamers

“…Some important milestones have indeed been achieved. For example, α-peptidic tertiary folds and α-helix bundles have been shown to tolerate several β-amino-acids 11–16. Furthermore, helix bundles comprised of β-amino-acids17,18 or β-ureas,19 at the exclusion of any α-amino acid have also been described.…”

Controlling the conformational stability of coiled-coil peptides with a single stereogenic center of a peripheral β-amino acid residue

“…Although there are several studies on the effect of substitution of b-amino acids on conformational stability of secondary, tertiary or quaternary structures, 35,48,52 the comparison of analogues containing units of various stereochemistry are rare, and concerns only single a-helix. 53 Here, we applied wellunderstood coiled-coil structure as a model for better understanding of effects of trans-ACPC and cis-ACPC substitutions on its conformational stability.…”

Design and Engineering of Miniproteins

“…The field of miniprotein design based on native folds was greatly expanded by the development of foldamer chemistry. , Since the late 1990s, many secondary structures formed by peptidomimetic sequences were obtained, and the rules for designing helices, strands, and turns have been well-described. − Recently, the concept of joining stable amphiphilic secondary structures together was applied for noncanonical secondary structures incorporating constrained β-amino acid. The helix–loop–helix structures were built from 9/12/9/10-helices containing cis -2-aminocyclopentanecarboxylic acid ( cis -ACPC) amino acids and a flexible oligo-Gly linker. , This rationale was also used to construct the foldameric helix–turn–helix structure . The use of a very rigid turn required a combinatorial calculation of possible spatial arrangements of the secondary structures based on experimental data of the torsions within the helix and the extended structure of the turn.…”