Investigations into biochemical mode of inhibition of guanase by azepinomycin: synthesis and biochemical screening of several analogues of azepinomycin.
In an effort to biochemical mode of guanase inhibition as well as the structure-activity relationships of azepinomycin, five analogues (I-V) of azepinomycin were synthesized and screened against guanase from rabbit liver. Our results suggest that while the 6-hydroxy group of azepinomycin is crucial for activity, its putative transition state mode of inhibition of guanase is questionable. The additional H-bonding sites at position 5, and hydrophobic groups in and around position 3 of azepinomycin appear to be tolerated, and may in fact enhance the potency of inhibition.
Rajappan
V P
VP
Department of Chemistry & Biochemistry, University of Maryland, Baltimore County (UMBC) 21250, USA.
Hosmane
R S
RS
D001381:Azepines / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D004791:Enzyme Inhibitors / Q000138:chemical synthesis* / Q000737:chemistry / Q000494:pharmacology; D006148:Guanine Deaminase / Q000037:antagonists & inhibitors*
D001381:Azepines; D004791:Enzyme Inhibitors; C054358:azepinomycin; D006148:Guanine Deaminase