Design and Synthesis of Peptides with Hybrid Helix-Turn-Helix (HTH) Motif and Their Conformational Study

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 beta-, gamma-, and delta-amino acids with carbohydrate side chains and alpha-amino acid, L-Ala. The alpha/beta-peptides were prepared from (S)-beta-Caa((i)) (C-linked carbo-beta-amino acid with D-lyxo furanoside side chain) and L-Ala with a 1:1 alternation. The alpha/beta-peptides with "helix-turn" motif displayed a 11/9-helix nucleating a 13-atom H-bonding turn. The alpha/beta-octapeptides showed the presence of HTH structures with bifurcated 11/15-H-bonded turn. Further, the alpha/beta-hexapeptide with HT motif, independently on coupling with gamma/alpha/gamma/alpha- and delta/alpha/delta/alpha-tetrapeptides at the C-terminus provided access to the decapeptides with "hybrid HTH" motifs. The decapeptide ("alpha-beta-alpha-beta-alpha-beta-gamma-alpha-gamma-alpha") showed a hybrid HTH with "11/9/11/9/11/16/9/12/10" H-bonding, while the decapeptide ("alpha-beta-alpha-beta-alpha-beta-delta-alpha-delta-alpha") 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.