Epoxide opening in water and screening in situ for rapid discovery of enzyme inhibitors in microtiter plates.
A method utilizing the strategy of epoxide opening by amine with water as co-solvent and screening in situ was developed for rapid discovery of protein inhibitors. Using this approach, HIV protease inhibitors with novel P1' residues were identified in our study. This strategy should be applicable for the efficient assembly of diverse compound collections for inhibitors' discovery and optimization in other systems.
Liang
Fu-Sen
FS
Department of Chemistry, The Skaggs Institute of Chemical Biology, The Scripps Research Institute, La Jolla, CA 92037, USA.
Brik
Ashraf
A
Lin
Ying-Chuan
YC
Elder
John H
JH
Wong
Chi-Huey
CH
D000577:Amides / Q000737:chemistry; D000588:Amines / Q000737:chemistry; D004353:Drug Evaluation, Preclinical / Q000295:instrumentation* / Q000379:methods*; D004852:Epoxy Compounds / Q000737:chemistry*; D017320:HIV Protease Inhibitors / Q000138:chemical synthesis / Q000737:chemistry* / Q000494:pharmacology*; D006900:Hydroxylation; D015394:Molecular Structure; D013329:Structure-Activity Relationship; D013997:Time Factors; D014867:Water / Q000737:chemistry*
D000577:Amides; D000588:Amines; D004852:Epoxy Compounds; D017320:HIV Protease Inhibitors; D014867:Water