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 ß-, γ-, and δ-amino acids with carbohydrate side chains and α-amino acid, L-Ala. The α/ß-peptides were prepared from (S)-ß-Caa(l) (C-linked carbo-ß-amino acid with D-lyxo furanoside side chain) and L-Ala with a 1:1 alternation. The α/ß-peptides with "helix-turn" motif displayed a 11/9-helix nucleating a 13-atom H-bonding turn. The α/ß-octapeptides showed the presence of HTH structures with bifurcated 11/15-H-bonded turn. Further, the α/ß-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-ß-α-ß-α-ß-γ-α-γ-α") showed a hybrid HTH with "11/9/11/9/11/16/9/12/10" H-bonding, while the decapeptide ("α-ß-α-ß-α-ß-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.

Design and synthesis of trans-3-aminopyran-2-carboxylic acid (APyC) and α/ß-peptides with 9/11-helix.

A new ß-amino acid, trans-3-aminopyran-2-carboxylic acid (APyC), was designed and synthesized from (R)-glyceraldehyde derivative and used in the synthesis of α/ß-peptides in a 1 : 1 alternating pattern with d-Ala. The presence of oxygen atom at the Cß(2)-position in APyC was envisaged to provide opportunity for additional interaction. These hybrid peptides have shown the presence of 9/11-helix through extensive NMR and MD studies. The amide protons of d-Ala, in addition to participating in 9-mr H-bonding with CO of succeeding ß-residue, were also involved in additional electrostatic interaction with pyran ring oxygen of preceding ß-residue, which facilitated further stabilization to the 9/11-mixed helix. The study thus results in a new 'motif' for a 9/11-helix, and the first example from a cyclic ß-amino acid.

The design of α/ß-peptides: study on three-residue turn motifs and the influence of achiral glycine on helix and turn.

Novel three-residue helix-turn secondary structures, nucleated by a helix at the N terminus, were generated in peptides that have 'ß-Caa-L-Ala-L-Ala,' 'ß-Caa-L-Ala-γ-Caa,' and 'ß-Caa-L-Ala-δ-Caa' (in which ß-Caa is C-linked carbo-ß-amino acid, γ-Caa is C-linked carbo-γ-amino acid, and δ-Caa is C-linked carbo-δ-amino acid) at the C terminus. These turn structures are stabilized by 12-, 14-, and 15-membered (mr) hydrogen bonding between NH(i)/CO(i+2) (i+2 is the last residue in the peptide) along with a 7-mr hydrogen bond between CO(i)/NH(i+2). In addition, a series of α/ß-peptides were designed and synthesized with alternating glycine (Gly) and (S)-ß-Caa to study the influence of an achiral α-residue on the helix and helix-turn structures. In contrast to previous results, the three 'ß-α-ß' residues at the C terminus (α-residue being Gly) are stabilized by only a 13-mr forward hydrogen bond, which resembles an α-turn. Extensive NMR spectroscopic and molecular dynamics (MD) studies were performed to support these observations. The influence of chirality and side chain is also discussed.

Versatile intramolecular aza-Prins and Prins cyclization of aryl epoxides: a facile synthesis of diaza-, oxa-aza-, and dioxa-bicycles.

Aryl epoxides undergo coupling smoothly with (E)-hex-3-ene-1,6-ditosylamide in the presence of 10 mol % p-TSA in 1,2-dichloroethane at 75 degrees C to produce the corresponding 1,5-ditosyl-octahydro-1H-pyrrolidino[3,2-c]pyridines in good yields with high trans-selectivity, whereas the coupling of (Z)-hex-3-ene-1,6-ditosylamide gave cis-fused octahydro-1H-pyrrolidino[3,2-c]pyridines predominantly. The use of readily available p-TSA makes this method simple, convenient, and practical.

Three-component reaction of aldose sugars, aryl amines, and 1,3-diones: a novel synthesis of annulated pyrroles.

Aldose sugars undergo smooth coupling with enamines, generated in situ from aryl amines and 1,3-diketones, in the presence of 10 mol % of InCl3 in water at 80 degrees C to furnish annulated pyrrole derivatives in relatively good to high yields. The use of InCl3, in combination with water, makes this procedure quite simple, more convenient, and environmentally friendly.