Conformational Effects through Hydrogen Bonding in a Constrained γ-Peptide Template: From Intraresidue Seven-Membered Rings to a Gel-Forming Sheet Structure

Abstract

A series of three short oligomers (di-, tri-, and tetramers) of cis-2-(aminomethyl)cyclobutane carboxylic acid, a γ-amino acid featuring a cyclobutane ring constraint, were prepared, and their conformational behavior was examined spectroscopically and by molecular modeling. In dilute solutions, these peptides showed a number of low-energy conformers, including ribbonlike structures pleated around a rarely observed series of intramolecular seven-membered hydrogen bonds. In more concentrated solutions, these interactions defer to an organized supramolecular assembly, leading to thermoreversible organogel formation notably for the tripeptide, which produced fibrillar xerogels. In the solid state, the dipeptide adopted a fully extended conformation featuring a one-dimensional network of intermolecularly H-bonded molecules stacked in an antiparallel sheet alignment. This work provides unique insight into the interplay between inter- and intramolecular H-bonded conformer topologies for the same peptide template.

Carbocycle-Based Organogelators: Influence of Chirality and Structural Features on Their Supramolecular Arrangements and Properties

“…Non-polar H atoms were omitted for cla Adapted with permission of Elsevier [52]. Furthermore, the ability as organogelators of peptidomimetics made up w rigid cyclobutane-containig γ-amino acids has also been examined [53]. Short ol 32a-c were synthesized from cis (1R,2S)-2-(aminomethyl)cyclobutane-1-carboxy [54] (Figure 22).…”

Synthesis of Chiral Scaffolds Based on Polyfunctional Cyclobutane β‐Amino Acids

“…[1,2,3] Cyclobutane amino acids (CBAAs) are an interesting class of molecules that include both naturally occurring [4] and synthetic products and, accordingly, many efforts have been devoted to the preparation and applications of cyclobutane α-, [5] β-, [6,7] and γ-amino acids. [8][9][10][11] In particular, the derivatives obtained from (R,S)-and (S,S)-2-aminocyclobutane-1-carboxylic acids ((R,S)and (S,S)-β-CBAA, respectively) [6,7] (Figure 1) have been revealed as powerful synthetic precursors of manifold products. When incorporated in homo or hybrid peptides, β-CBAAs can be useful as chiral polyfunctional platforms to produce different products as well as soft materials with specific features.…”

A solvation induced ring puckering effect in fluorinated prolines and its inclusion in classical force-fields

“…However, the influence of H-bonding 17 and charge fluxes induced by solvent have been shown to be crucial for treating conformational equilibria in furanose rings 18 (carbohydrates) and peptides containing cyclobutane. 19 On the other hand, classical force-fields include explicit solvent but do not capture solute conformational properties accurately, especially, puckering of substituted rings. Incorporation of a pucker correction based on accurate quantum mechanical calculations could potentially fix classical force-fields and make the best of both worlds.…”