Interactions of glycoproteins with their cellular environments, impacts on a wide range of physiological phenomena.[1] It is predicted that over half eukaryotic proteins are glycosylated and it is known that co- and post-translational modification of proteins with glycans has dramatic consequences on their folding, stability and ultimately, their function. Important insights into such phenomena have been gleaned from the study of glycopeptide- and oligosaccharide-mimetics and especially those that are structurally well defined. However, attempts to correlate secondary structures with the biological activities of non-multivalent glycopeptide mimetics have been relatively sparse despite the importance of such targets in the quest for carbohydrate-based therapeutics.
In the present work we sought to examine the effects of appended sugar moieties on the conformational behavior of a family of delta-sugar amino acid (delta-SAA)-derived foldamers.[2] Foldamers are synthetic oligomers able to adopt ordered conformations in solution and their study has helped enlighten our understanding of the origins of the preferred secondary structures and biological activities of polymers prevalent in Nature.[3] We here examine the secondary structures adopted by various delta-SAA-derived foldamer backbones either appended and not with selected sugar moieties. We also show the impact of the conformational preferences manifested in water by these delta-glycofoldamers on their non-multivalent interactions with model protein targets.
[1] (a) Larkin, A.; Imperiali, B., Biochemistry, 2011, 50, 4411; (b) Price, J. L.; Powers, D. L.; Powers, E. T.; Kelley, J. W., PNAS, 2011, 108, 14127 .
[2] Chakraborty, T. K.: Srinivasu, P.; Tapadar, S.; Mohan, B. K., Glycoconjug. J., 2005, 22, 83.
[3] (a) Gellman, S. H., Acc. Chem. Res., 1998, 31, 173; (b) Goodman, C. A.; Choi, S.; Shandler, S.; DeGrado, W. F., , Nature Chemical Biology 2007, 3, 252; (c) Guichard, G.; Huc, I., Chem. Comm, 2011, 47, 5933 and references cited therein.
