Global transformation of OBOC combinatorial peptide libraries into OBOC polyamine and small molecule libraries

Joseph C. Kappel, Yi C. Fan, Kit Lam

Research output: Contribution to journalArticle

7 Scopus citations

Abstract

In "one-bead-one-compound" (OBOC) combinatorial chemistry, a compound-bead library with hundreds of thousands to millions of diversities can be rapidly generated such that each bead displays only one chemical entity. The highly efficient "libraries-from-libraries" approach involves the global transformation of a peptide library into many small molecule solution-phase mixture libraries, but this approach has never been successfully applied to OBOC libraries. Here we report a novel approach that allows us to combine these two enabling technologies to efficiently generate OBOC encoded small molecule bead libraries. By using a topologically segregated bilayer bead and a "ladder-synthesis" method, we can prepare peptide libraries with the peptide on the bead surface and a series of peptide ladders in the bead interior. Various global transformation reactions can then be employed to transform the starting peptide library into a variety of peptidomimetic libraries. During the transformation reactions, the peptide ladders in the bead interior are also transformed in a predictable manner. As a result, individual compound bead can be decoded by analyzing the hydrogen fluoride-released encoding tags with matrix-assisted laser desorption ionization Fourier transform mass spectrometry. Using this novel approach, a random encoded dipeptide library was prepared and subsequently transformed into polyamine and poly-N-acetylamine sublibraries. Random beads isolated from these sublibraries were reliably decoded.

Original languageEnglish (US)
Pages (from-to)333-342
Number of pages10
JournalJournal of Combinatorial Chemistry
Volume10
Issue number2
DOIs
StatePublished - Mar 2008

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Chemistry(all)
  • Discrete Mathematics and Combinatorics

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