Two comparisons of the performance of positional scanning and deletion synthesis for the identification of active constituents in mixture combinatorial libraries.
Two libraries of 120 compounds each were prepared as individual compounds and as full mixtures. The corresponding scanning and deletion synthesis deconvolution libraries were prepared and tested (L-1210, IC(50)) alongside the individual compounds and mixture libraries. This testing, where the properties of each compound in the mixtures were known, was used to compare the performance of scanning and deletion deconvolution libraries. Each has its own intrinsic strengths, with the former being capable of identifying multiple hits at the expense of accurately identifying the most potent library member, while the latter typically is more sensitive to identifying the most potent hit but at the expense of differentiating weaker activities. The protocols complement one another and together more thoroughly identify potent library members.
Boger
D L
DL
Department of Chemistry and The Skaggs Institute for Chemical Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, California 92037, USA.
Lee
J K
JK
Goldberg
J
J
Jin
Q
Q
D000818:Animals; D000970:Antineoplastic Agents / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D020128:Inhibitory Concentration 50; D051379:Mice; D018716:Molecular Mimicry; D009842:Oligopeptides / Q000037:antagonists & inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000378:metabolism / Q000494:pharmacology; D019151:Peptide Library; D019030:Receptors, Vitronectin / Q000037:antagonists & inhibitors / Q000737:chemistry; D017384:Sequence Deletion; D014407:Tumor Cells, Cultured
D000970:Antineoplastic Agents; D009842:Oligopeptides; D019151:Peptide Library; D019030:Receptors, Vitronectin; C047981:arginyl-glycyl-aspartic acid