Carbopeptides: Carbohydrates as potential templates for de novo design of protein models

Knud J. Jensen, George Barany

Research output: Contribution to journalArticlepeer-review

23 Scopus citations

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 α-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 (N(β)-Fmoc-βAla)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 β-glycosidic carbohydrate template (N(β)-Fmoc-βAla)4-β-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.

Original languageEnglish (US)
Pages (from-to)3-11
Number of pages9
JournalJournal of Peptide Research
Volume56
Issue number1
DOIs
StatePublished - 2000

Keywords

  • Carbohydrate
  • De novo design
  • Peptide
  • Solid-phase synthesis

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