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Titolo:
Synthesis and evaluation of dipeptide amides containing N-omega-nitroarginine and D-2,4-diaminobutyric acids as inhibitors of neuronal nitric oxide synthase
Autore:
Huang, H; Martasek, P; Roman, LJ; Silverman, RB;
Indirizzi:
Northwestern Univ, Dept Chem, Evanston, IL 60208 USA Northwestern Univ Evanston IL USA 60208 Dept Chem, Evanston, IL 60208 USA Northwestern Univ, Dept Biochem Mol Biol & Cell Biol, Evanston, IL 60208 USA Northwestern Univ Evanston IL USA 60208 Cell Biol, Evanston, IL 60208 USA Univ Texas, Hlth Sci Ctr, Dept Biochem, San Antonio, TX 78284 USA Univ Texas San Antonio TX USA 78284 pt Biochem, San Antonio, TX 78284 USA
Titolo Testata:
JOURNAL OF ENZYME INHIBITION
fascicolo: 3, volume: 16, anno: 2001,
pagine: 233 - 239
SICI:
8755-5093(2001)16:3<233:SAEODA>2.0.ZU;2-C
Fonte:
ISI
Lingua:
ENG
Soggetto:
ENDOR SPECTROSCOPIC EVIDENCE; SELECTIVE INHIBITORS; ESCHERICHIA-COLI; L-ARGININE; IN-VIVO; EXPRESSION; BINDING; POTENT;
Keywords:
dipeptide amide; nitric oxide synthase; nitroarginine; D-2,4-diaminobutyric acid; enzyme inhibition;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
26
Recensione:
Indirizzi per estratti:
Indirizzo: Silverman, RB Northwestern Univ, Dept Chem, 2145 Sheridan Rd, Evanston, IL60208 USA Northwestern Univ 2145 Sheridan Rd Evanston IL USA 60208 USA
Citazione:
H. Huang et al., "Synthesis and evaluation of dipeptide amides containing N-omega-nitroarginine and D-2,4-diaminobutyric acids as inhibitors of neuronal nitric oxide synthase", J ENZ INHIB, 16(3), 2001, pp. 233-239

Abstract

Selective inhibition of the isoforms of nitric oxide synthase (NOS) could be beneficial in the treatment of certain disease states arising from the overproduction of nitric oxide by NOS. Recently, we reported dipeptide amides containing a basic amine side chain as potent and selective inhibitors ofneuronal NOS (Huang, H. et al. (1999) J. Med. Chem., 42, 3147). The most potent nNOS inhibitor among these compounds is L-Arg (NO2)-L-Dbu-NH2 (1) (K-i = 130 nM), which also exhibits the highest selectivity over eNOS (> 1500-fold). The D,D-dipeptide, D-LyS-D-Arg(NO2)-NH2 (3) also shows high potency and selectivity. Here the dipeptide amides containing Arg(NO2) and D-Dbu (9-12) were synthesized and evaluated. They are all modest inhibitors of nNOS, but poor inhibitors of eNOS and iNOS. D-DbU-D-Arg(NO2)-NH2 (12) exhibits decreased inhibitory potency as compared with 3. A hypothesis regarding thebinding at the active site of nNOS is proposed to explain the potency differences between the L- and D-form dipeptide amides.

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Documento generato il 04/08/20 alle ore 22:32:52