Application of combinatorial library methods in cancer research and drug discovery

Research output: Contribution to journalArticle

79 Citations (Scopus)

Abstract

Combinatorial chemistry is now considered as one of the most important recent advances in medicinal chemistry. There are five general approaches in combinatorial. peptide library methods: biological libraries; spatially addressable parallel solid phase or solution phase libraries; synthetic library methods requiring deconvolution; the 'one-bead one-compound' library method; and synthetic library methods using affinity chromatography selection. Except for the biological library approach, which is limited to peptide libraries with eukaryotic amino acids, all the other four synthetic approaches are applicable to peptide, non-peptide oligomer or small molecule libraries. Although non-peptide or small molecule libraries are generally prepared by a synthetic approach, recent advances in biosynthetic methods using enzymes may enable one to prepare chemical libraries that are otherwise difficult to synthesize chemically. In the 'one-bead one-compound' library method every member of the library is screened in parallel, but the chemical structure of the positive compound-bead has to be determined either directly or via an encoding strategy. A reliable high-throughput biological assay is needed for a successful combinatorial library screen. Solid-phase binding or functional assays as well as solution phase assays have been used successfully in various library methods. There has been enormous progress in the technological advances of molecular biology and the fundamental understanding of the molecular basis of cancer in recent years. By applying combinatorial chemistry and computational chemistry to the many cancer targets that have recently been identified, it is hopeful that more potent, more specific and less toxic anti-cancer agents will be developed in the foreseeable future. In addition to being a great tool for drug discovery, combinatorial chemistry has also proven to be invaluable in basic research. A few specific examples of the applications of combinatorial chemistry in basic cancer research and drug discovery are described in this mini-review.

Original languageEnglish (US)
Pages (from-to)145-167
Number of pages23
JournalAnti-Cancer Drug Design
Volume12
Issue number3
StatePublished - 1997
Externally publishedYes

Fingerprint

Drug Discovery
Libraries
Research
Small Molecule Libraries
Neoplasms
Peptide Library
Assays
High-Throughput Screening Assays
Pharmaceutical Chemistry
Poisons
Computational chemistry
Affinity Chromatography
Affinity chromatography
Molecular biology
Molecules
Molecular Biology
Deconvolution
Oligomers
Amino Acids
Peptides

Keywords

  • Cancer targets
  • Combinatorial chemistry
  • Drug discovery
  • Peptide and chemical libraries

ASJC Scopus subject areas

  • Drug Discovery
  • Organic Chemistry
  • Oncology
  • Biochemistry, Genetics and Molecular Biology(all)
  • Biochemistry
  • Pharmacology

Cite this

Application of combinatorial library methods in cancer research and drug discovery. / Lam, Kit.

In: Anti-Cancer Drug Design, Vol. 12, No. 3, 1997, p. 145-167.

Research output: Contribution to journalArticle

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