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 Citations (Scopus)

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

Fingerprint

Small Molecule Libraries
Polyamines
Peptide Library
Peptides
Libraries
Molecules
Ladders
Hydrofluoric Acid
Peptidomimetics
Dipeptides
Fourier Analysis
Mass Spectrometry
Lasers
Interior
Technology
Combinatorial Chemistry
Ionization
Mass spectrometry
Desorption
Fourier transforms

ASJC Scopus subject areas

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

Cite this

Global transformation of OBOC combinatorial peptide libraries into OBOC polyamine and small molecule libraries. / Kappel, Joseph C.; Fan, Yi C.; Lam, Kit.

In: Journal of Combinatorial Chemistry, Vol. 10, No. 2, 03.2008, p. 333-342.

Research output: Contribution to journalArticle

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