The study describes the synthesis of new beta(2,2)-peptides made from geminally disubstituted beta(2,2)-amino acid and their folding propensities. The (R)-C-linked carbo-beta(2,2)-amino acid [(R)-beta(2,2)-Caa] was prepared from D-glucose and converted into the homo-oligomeric di-, tetra-, and hexapeptides. The conformational studies were carried out using NMR (in CDCl3), CD, IR, and MD calculations. These beta(2,2)-peptides were interestingly stabilized by five-membered (mr) inter-residue H-bonds NH(i)center dot center dot center dot O(i-1) (furanoside) and a 6-mr intra-residue H-bond between amide proton (NH(i)) and the oxygen of -OMe(i) at the C3 carbon of the carbohydrate side chain. These results amply demonstrate that the 'epimerization' at the spiro carbon center has an effect on the conformational behavior of these peptides. Finding of these, H-bonding patterns, which are not so common to stabilize the folds in this class of beta(2,2)-Caa derived peptides would further facilitate augmentation in the domain of foldamer. (C) 2012 Elsevier Ltd. All rights reserved.
