Design and synthesis of peptides with hybrid helix-turn-helix (HTH) motif and their conformational study.

Abstract

The present study is aimed at the design and synthesis of peptides with hybrid helix-turn-helix (HTH) motif and their conformational analysis (NMR, MD, and CD studies). The requisite peptides with heterogeneous backbones were prepared from β-, γ-, and δ-amino acids with carbohydrate side chains and α-amino acid, L-Ala. The α/β-peptides were prepared from (S)-β-Caa(l) (C-linked carbo-β-amino acid with D-lyxo furanoside side chain) and L-Ala with a 1:1 alternation. The α/β-peptides with "helix-turn" motif displayed a 11/9-helix nucleating a 13-atom H-bonding turn. The α/β-octapeptides showed the presence of HTH structures with bifurcated 11/15-H-bonded turn. Further, the α/β-hexapeptide with HT motif, independently on coupling with γ/α/γ/α- and δ/α/δ/α-tetrapeptides at the C-terminus provided access to the decapeptides with "hybrid HTH" motifs. The decapeptide ("α-β-α-β-α-β-γ-α-γ-α") showed a hybrid HTH with "11/9/11/9/11/16/9/12/10" H-bonding, while the decapeptide ("α-β-α-β-α-β-δ-α-δ-α") revealed the presence of a "11/9/11/9/11/17/9/13/11" helical pattern. The above peptides thus have shown compatibility between different types of helices and serendipitous bifurcated 11/16- and 11/17-turns. The present study thus provided the first opportunity for the design and study of "hybrid HTH" motifs with more than one kind of helical structures in them.