Relationship between side-chain branching and stoichiometry in β3-peptide bundles

Abstract

The stability and stoichiometry of β3-peptide bundles is influenced by side-chain identity. β3-peptides containing β3-homoleucine on one helical face assemble into octamers, whereas those containing β3-homovaline form tetramers. From a structural perspective, the side chains of β3-homoleucine and β3-homovaline differ in terms of both side-chain length and γ-carbon branching. To evaluate the extent to which these two parameters control β3-peptide bundle stoichiometry, we synthesized the β3-peptide Acid-3Y, which contains β3-homoisoleucine in place of β3-homoleucine or β3-homovaline. Acid-3Y assembles into a stable tetramer whose stability resembles that of the previously characterized Acid-VY tetramer. These results suggest that β3-peptide bundle stoichiometry is dominated by the presence or absence of γ-carbon branching on core side chains.

Positive Allostery in Metal Ion Binding by a Cooperatively Folded β-Peptide Bundle

“…Synthetic β 3 -peptide oligomers possessing a spectrum of biomimetic properties have been reported. − These properties include the formation of ordered, monomeric helices in water that interact selectively with helix-binding clefts on native proteins ,, and protein partnerships . Others include that of self-assembly into cooperatively folded, thermally stable, octameric or tetrameric helical bundles. − β 3 -peptide bundles possessing incipient catalytic activity have also been reported, including the ability to sequester polyols, catalyze esterolysis, and promote the aldol reaction, all in water.…”

Design and High-Resolution Structure of a β3-Peptide Bundle Catalyst

“…We next investigated the dependence of catalytic activity on β 3 -peptide bundle stoichiometry. As previously reported, there exists a direct relationship between bundle stoichiometry and β 3 -peptide sequence; specifically, β 3 -peptides with β 3 L residues at positions i , i +3, i +6, and i +9 assemble into octamers, those with β 3 V or β 3 I at these positions assemble into tetramers, and those with β 3 A at these positions are constitutively monomeric . Based on this relationship, we synthesized two stoichiometric variants of βEst-2C, one containing an all-valine face and another containing an all-alanine face (βEst-2C-V and βEst-2C-A in Figure C, respectively).…”

Novel Materials From the Supramolecular Self-Assembly of Short Helical β3-Peptide Foldamers

“…Prior to the recent reports of supramolecular self-assembly of β 3 -peptides, a number of groups have demonstrated the assembly of β 3 -peptides into bundles containing 4–10 individual β 3 -peptides (Raguse et al, 2001; Daniels et al, 2007; Goodman et al, 2007, 2008; Giuliano et al, 2009; Wang et al, 2012, 2014; Wang and Schepartz, 2016). A β 3 -peptide bundle arises from the cooperative folding of β 3 -peptides into higher-order quaternary assemblies in solution and exhibit protein-like properties in which the hydrophobic surfaces are buried in the interior core.…”