Ds. Thorpe et al., Efficient discovery of inhibitory ligands for diverse targets from a smallcombinatorial chemical library of chimeric molecules, BIOC BIOP R, 266(1), 1999, pp. 62-65
Citations number
15
Categorie Soggetti
Biochemistry & Biophysics
Journal title
BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS
Living systems are mainly composed and regulated by compounds in four bioch
emical classes and their polymers-nucleotides, carbohydrates, lipids, and a
mino acids. Early combinatorial chemistry libraries consisted of peptides.
The present report describes the general bioactivity and biophysical proper
ties 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 hig
her than a commonly claimed industrial benchmark of 0.02%. It produced 7 st
ructurally confirmed hits for a third of 12 proprietary drug discovery proj
ects, and these comprised a variety of molecular targets. Diversity analyse
s demonstrated that despite the small number of compounds, a wider range of
diversity space was covered by this library of biochemical chimeras than b
y a branched tripeptide library of the same size and similar generic formul
a. (C) 1999 Academic Press.