Design of inhibitors against guanase: synthesis and biochemical evaluation of analogues of azepinomycin.
As part of a program to design rational, mechanism-based inhibitors of guanase, we report here the synthesis and biochemical screening of two analogues of azepinomycin (1 and 2), a naturally occurring inhibitor of guanase, known to mimic the transition-state of the enzyme-catalyzed reaction. Our biochemical results show that compounds 1 and 2 are competitive inhibitors with K(i) of 2.01+/-0.16 x 10(-5) and 5.36+/-0.14 x 10(-5) M, respectively.
Ujjinamatada
Ravi K
RK
Laboratory for Drug Design and Synthesis, Department of Chemistry and Biochemistry, University of Maryland, Baltimore County, 1000 Hilltop Circle, Baltimore, MD 21250, USA.
Bhan
Anila
A
Hosmane
Ramachandra S
RS
D000818:Animals; D001381:Azepines / Q000138:chemical synthesis* / Q000494:pharmacology*; D006148:Guanine Deaminase / Q000037:antagonists & inhibitors*; D011817:Rabbits
D001381:Azepines; C054358:azepinomycin; D006148:Guanine Deaminase