mABA inserted supramolecular triple helix formation in the solid state in synthetic tripeptides containing β-cyanoalanine and Aib as corner residues

Abstract

Single crystal X-ray diffraction studies reveal that the two terminally protected tripeptides Boc-β-cyano-Ala-Aib-mABA-OMe (I) and Boc-β-hydroxy-Ala-Aib-mABA-OMe (II) with a centrally positioned non-coded amino acid Aib (α-aminoisobutyric acid) and a conformationally constrained mABA (meta-aminobenzoic acid) at the C-terminus, adopt a type II′ β-turn conformation in the solid state, rarely observed in tripeptides. Interestingly, the type II′ β-turn molecules of peptide I self-assemble to form a triple helical assemblage using hydrogen bonding and various non-covalent interactions in the solid state. In contrast, the tripeptide II, exhibiting conformational preference for a type II′ β-turn, does not support the formation of such a triple helical architecture. Instead a double helical assembly is formed, thus emphasizing the importance of the cyanomethyl moiety in triple helix stabilization. To date a significant amount of work has been performed in designing triple helical motifs either using metal co-ordinated complexes or rigid organic templates. However, to the best of our knowledge, this novel example is one of the very few reports of supramolecular triple helix design resulting from the self assembly of a tripeptide solely nucleated by conformational features, namely a type II′ β-turn in the synthesized tripeptides.