K. Jensen, G. Barany
Jul 1, 2000
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0
Influential Citations
19
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Journal
The journal of peptide research : official journal of the American Peptide Society
Abstract
De novo design of proteins has evolved into a powerful approach for studying the factors governing protein folding and stability. Among the families of structures frequently studied is the 'four-helix bundle' in which four alpha-helical peptide strands, linked by loops, form a hydrophobic core. Assembly of protein models on a template has been suggested as a way to reduce the entropy of folding. Here we describe the potential use of a carbohydrate as such a template. The monosaccharide D-galactose was per-O-acylated with (Nbeta-Fmoc-betaAla)2O to give a penta-substituted derivative, which was converted to the corresponding glycosyl bromide and used for the glycosylation of 4-hydroxymethylbenzoic acid pentafluorophenyl ester (HMBA-OPfp). The beta-glycosidic carbohydrate template (Nbeta-Fmoc-3Ala)4-beta-D-Galp-(1-O)-MBA-OPfp thus obtained was coupled to a PAL-PEG-PS resin and simultaneously extended at the four arms to yield, after cleavage from the solid support, a carbopeptide with four identical peptide strands. Extension of this concept to, for example, synthesis of novel multiple antigenic peptides (MAPs) and synthesis of carbohydrate clusters can be easily envisioned. The ability to efficiently synthesize such structures sets the stage for further studies to test whether the carbohydrate templates do indeed nucleate folding.