Antiparallel Self‐Association of a γ,α‐Hybrid Peptide: More Relevance of Weak Interactions

Abstract

To learn how a preorganized peptide-based molecular template, together with diverse weak non-covalent interactions, leads to an effective self-association, we investigated the conformational characteristics of a simple γ,α-hybrid model peptide, Boc-γ-Abz-Gly-OMe. The single-crystal X-ray diffraction analysis revealed the existence of a fully extended β-strand-like structure stabilized by two non-conventional C-H⋅⋅⋅O=C intramolecular H-bonds. The 2D (1) H NMR ROESY experiment led us to propose that the flat topology of the urethane-γ-Abz-amide moiety is predominantly preserved in a non-polar environment. The self-association of the energetically more favorable antiparallel β-strand-mimic in solid-state engenders an unusual 'flight of stairs' fabricated through face-to-face and edge-to-edge Ar⋅⋅⋅Ar interactions. In conjunction with FT-IR spectroscopic analysis in chloroform, we highlight that conformationally semi-rigid γ-Abz foldamer in appositely designed peptides may encourage unusual β-strand or β-sheet-like self-association and supramolecular organization stabilized via weak attractive forces.

Modulating Hydrogen Bonded Self-assembled Patterns and Morphological Features by a Change in Side Chain of Third Amino Acid of Synthetic γ- Amino Acid Based Tripeptides

“…These inter‐residual interactions lead to form parallel sheet‐type of architecture along crystallographic a axis. At higher‐order self‐assembly, the sheets formed by peptide subunits are interconnected via week C–H⋅⋅⋅O (14C=O3⋅⋅⋅H21C–C21, C⋅⋅⋅O=3.07 Å, C−H⋅⋅⋅O=2.58 Å and angle ∢C−H⋅⋅⋅O=110.7°) intermolecular hydrogen‐bond interactions along the crystallographic b axis leading to form supramolecular higher order architecture …”

“…Thus, this interaction between Aib(2)C=O and H–N Aib(2) of another subunit is responsible for the alignment of repeated peptide subunits to form supramolecular sheets along crystallographic a axis (see the Supporting Information, Figure S4 and S5). Further, these sheets are associated via week C–H⋅⋅⋅O (5C=O2⋅⋅⋅H21B–C21, C⋅⋅⋅O=3.38 Å, C−H⋅⋅⋅O=2.44 Å and angle ∢C−H⋅⋅⋅O=158.4°) interactions along the crystallographic c axis leading to form supramolecular higher order architecture …”

“…At higher-order self-assembly, the sheets formed by peptide subunits are interconnected via week C-H···O (14C=O3···H21C-C21, C···O = 3.07 , CÀH···O = 2.58 and angle aCÀH···O = 110.78) intermolecular hydrogen-bond interactions along the crystallographic b axis leading to form supramolecular higher order architecture. [86][87][88][89] Close investigation of the crystal structure of peptide 2 demonstrates that only one intermolecular hydrogen bond is present between two peptide subunits. The hydrogen bond arises from carbonyl group C=O Aib(2) residue of one peptide unit and H-N group of Aib(2) of an adjacent subunit.…”

“…Further, these sheets are associated via week C-H···O (5C= O2···H21B-C21, C···O = 3.38 , CÀH···O = 2.44 and angle aCÀ H···O = 158.48) interactions along the crystallographic c axis leading to form supramolecular higher order architecture. [86][87][88][89]…”

Advances in hybrid peptide-based self-assembly systems and their applications

“…Along with these interactions, the crystal structure was also stabilized by face-to-face and edge-to-edge Ar⋯ interactions between γ-Abz groups. 198…”