Isoform-selective substrates of nitric oxide synthase.
Because of the double-edged nature of NO, the development of isoform-selective NOS substrates is a highly desirable goal. Given the striking similarity in the heme active sites of the three NOS isoforms, it presents an challenging problem. Several N-aryl-N'-hydroxyguanidines have recently been shown as substrates that are selective for iNOS over nNOS. Here, we report the first success that 3 is a good substrate for nNOS (70% activity of NOHA, K(m) approximately 40 +/- 6 microM) over iNOS.
Jia
Qiang
Q
Department of Chemistry, Wayne State University, Detroit, Michigan 48202, USA.
Cai
Tingwei
T
Huang
Mingchuan
M
Li
Huiying
H
Xian
Ming
M
Poulos
Thomas L
TL
Wang
Peng G
PG
D006146:Guanidines / Q000138:chemical synthesis* / Q000737:chemistry; D006454:Hemoglobins / Q000737:chemistry; D007527:Isoenzymes / Q000737:chemistry; D019001:Nitric Oxide Synthase / Q000737:chemistry*; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II; D013329:Structure-Activity Relationship; D013379:Substrate Specificity
D006146:Guanidines; D006454:Hemoglobins; D007527:Isoenzymes; D019001:Nitric Oxide Synthase; D052248:Nitric Oxide Synthase Type I; D052247:Nitric Oxide Synthase Type II