Comparison of resin and solution screening methodologies in combinatorial chemistry and the identification of a 100 nM inhibitor of trypanothione reductase.
Two identical polyamine peptide conjugate libraries were screened against the parasitic enzyme trypanothione reductase. One of these libraries was in a solution format, while the other was resin-based and was used in two resin-based screens (a diminution assay and a direct bead screening). Potent inhibitors (100 nM) of trypanothione reductase were identified both in the solution screen and in the resin-based screens when using the PEGA resin of Meldal. Resin screening of both types failed to work with TentaGel resin. Importantly there was excellent agreement between the solution and resin-based assays, suggesting both methods are reliable for the screening of combinatorial libraries.
Smith
H K
HK
Department of Chemistry, University of Southampton, U.K.
Bradley
M
M
D020650:Combinatorial Chemistry Techniques / Q000379:methods*; D015195:Drug Design; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D009247:NADH, NADPH Oxidoreductases / Q000037:antagonists & inhibitors*; D019151:Peptide Library; D011073:Polyamines / Q000138:chemical synthesis* / Q000737:chemistry; D012116:Resins, Plant; D012996:Solutions; D014344:Trypanocidal Agents / Q000138:chemical synthesis* / Q000737:chemistry
D004791:Enzyme Inhibitors; D019151:Peptide Library; D011073:Polyamines; D012116:Resins, Plant; D012996:Solutions; D014344:Trypanocidal Agents; D009247:NADH, NADPH Oxidoreductases; C049608:trypanothione reductase