Efficient discovery of inhibitory ligands for diverse targets from a small combinatorial chemical library of chimeric molecules
| Autor: | L.Charlie Chen, Kenneth F. Wertman, James Spoonamore, Anna Robinson, Sydney Wilson, David S. Thorpe, Alan Binnie, Martha Ackerman-Berrier, Shelly Wade, Stefan Walle, Helen Yeoman, Qinyuan (Quincey) Wu, A.W. Edith Chan, David Rodwell |
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| Rok vydání: | 1999 |
| Předmět: |
Glycosylation
Biophysics Drug Evaluation Preclinical Tripeptide Ligands Biochemistry Sensitivity and Specificity Chemical library Substrate Specificity chemistry.chemical_compound Inhibitory Concentration 50 Peptide Library Endopeptidases Combinatorial Chemistry Techniques Binding site Enzyme Inhibitors Peptide library Molecular Biology Protein Kinase Inhibitors chemistry.chemical_classification Diamide Binding Sites Nucleotides Combinatorial biology Reproducibility of Results Hydrogen Bonding Cell Biology Lipid Metabolism Amino acid Molecular Weight chemistry Protein Kinases |
| Zdroj: | Biochemical and biophysical research communications. 266(1) |
| ISSN: | 0006-291X |
| Popis: | Living systems are mainly composed and regulated by compounds in four biochemical classes and their polymers-nucleotides, carbohydrates, lipids, and amino acids. Early combinatorial chemistry libraries consisted of peptides. The present report describes the general bioactivity and biophysical properties of a combinatorial chemical library that used glyco, nucleotidyl, and lipid building blocks. The resulting chimeric combinatorial library of 361 compounds had a confirmed cumulative hit rate of 0.16%, which is 8-fold higher than a commonly claimed industrial benchmark of 0. 02%. It produced 7 structurally confirmed hits for a third of 12 proprietary drug discovery projects, and these comprised a variety of molecular targets. Diversity analyses demonstrated that despite the small number of compounds, a wider range of diversity space was covered by this library of biochemical chimeras than by a branched tripeptide library of the same size and similar generic formula. |
| Databáze: | OpenAIRE |
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