| Abstract
| - Glycopeptides that mimic the action of oligosaccharides have been rapidly identified through theimplementation of combinatorial library methodology combined with a novel, easy, screening and analysismethod. A glycopeptide library containing three different glycosyl amino building blocks, Fmoc-Asn(β-Ac3GlcNAc)-OPfp (5), Fmoc-Thr(α-Ac4Man)-OPfp (6), and Fmoc-Thr[α-Ac4Man(1→3)α-2-O-Bz-4,6-Ac2Man]-OPfp (7), was synthesized by the portion-mixing method on PEGA solid support. The library was designed tofacilitate rapid and unambiguous analysis of the active glycopeptides detected during the high throughput-screening step. Consequently, the library was synthesized using the ladder synthesis approach and linked tothe solid support via a photolabile linker. The glycosyl amino acids were labeled with carboxylic acid tags toallow unambiguous identification of the glycan moiety. Photolytic release of active glycopeptide from theresin was induced by irradiation of the bead with the MALDI-TOF-MS laser, and analysis of the resultingspectrum presenting the ladder of glycopeptide fragments yielded the sequence of the active glycopeptide.Glycopeptide ligands were identified for the C-type lectin from Lathyrus odoratus by screening the fluorescent-labeled protein in a solid-phase binding assay of the PEGA resin-bound glycopeptide library. Of the severalglycopeptide ligands detected, most contained Man or GlcNAc, glycans that display specificity for the lectinin hemagglutination assays. The most active glycopeptides detected from the library screening were T(α-d-Man)ALKPTHV, LHGGFT(α-d-Man)HV, T(α-d-Man)EHKGSKV, GT(α-d-Man)FPGLAV, and T(α-d-Man)LFKGFHV.
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