Combinatorial synthesis of MUC1 glycopeptides: Polymer blotting facilitates chemical and enzymatic synthesis of highly complicated mucin glycopeptides

Masataka Fumoto, Hiroshi Hinou, Takashi Ohta, Takaomi Ito, Kuriko Yamada, Akio Takimoto, Hirosato Kondo, Hiroki Shimizu, Toshiyuki Inazu, Yoshiaki Nakahara, Shin Ichiro Nishimura

Research output: Contribution to journalArticlepeer-review

66 Citations (Scopus)

Abstract

The chemoselective polymer blotting method allows for rapid and efficient synthesis of glycopeptides based on a "catch and release" strategy between solid-phase and water-soluble polymer supports. We have developed a heterobifunctional linker sensitive to glutamic acid specific protease (BLase). The general procedure consists of five steps, namely (i) the solid-phase synthesis of glycopeptide containing BLase sensitive linker, (ii) subsequent deprotections and the release of the glycopeptide from the resin, (iii) chemoselective blotting of the glycopeptide intermediates in the presence of water-soluble polymers with oxylamino functional groups, (iv) sugar elongations using glycosyltransferases, and (v) the release of target glycopeptides from the polymer platform by selective BLase promoted hydrolysis. The combined use of the solid-phase chemical syntheses of peptides and the enzymatic syntheses of carbohydrates on water-soluble polymers would greatly contribute to the production of complicated glycopeptide libraries, thereby enhancing applicative research. We report here a high-throughput synthetic system for the various types of MUC1 glycopeptides exhibiting a variety of sugar moieties. It is our belief that this concept will become part of the entrenched repertoire for the synthesis of biologically important glycopeptides on the basis of glycosyltransferase reactions in automated and combinatorial syntheses.

Original languageEnglish
Pages (from-to)11804-11818
Number of pages15
JournalJournal of the American Chemical Society
Volume127
Issue number33
DOIs
Publication statusPublished - Aug 24 2005
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Catalysis
  • Chemistry(all)
  • Biochemistry
  • Colloid and Surface Chemistry

Fingerprint Dive into the research topics of 'Combinatorial synthesis of MUC1 glycopeptides: Polymer blotting facilitates chemical and enzymatic synthesis of highly complicated mucin glycopeptides'. Together they form a unique fingerprint.

Cite this