Blocked dihydropteridines as nitric oxide synthase activators

Craig R. McInnes, C.J. Suckling, C.L. Gibson, Raghavendar R. Morthala, Simon Daff, Ben Gazur

Research output: Contribution to journalArticle

2 Citations (Scopus)

Abstract

It has been shown that 6-acetyl-7,7-dimethyl-5,6,7,8-tetrahydropteridin-4(3H)-one can act as a competent cofactor for the production of nitric oxide by neuronal nitric oxide synthase (nNOS). More information was sought on the structural features that could contribute to strong binding within the enzyme whilst maintaining a fast electron transfer rate. This study was concerned with expansion at the C2-position of the pteridine scaffold. The evidence suggests that expansion at the C2-position had a deleterious effect with respect to Km and as a consequence electron transfer rate. Unexpectedly, several lines of evidence suggested that a methyl substituent on nitrogen at C2 reduced the electron density in the pyrimidine and dihydropterin rings.
LanguageEnglish
Pages27-35
Number of pages8
JournalPteridines
Volume20
Publication statusPublished - 2010

Fingerprint

Nitric Oxide Synthase
Pteridines
Electrons
Nitric Oxide Synthase Type I
Scaffolds
Carrier concentration
Nitric Oxide
Nitrogen
Enzymes
pyrimidine

Keywords

  • dihydropteridines
  • s nitric oxide
  • synthase activators
  • pteridines

Cite this

McInnes, C. R., Suckling, C. J., Gibson, C. L., Morthala, R. R., Daff, S., & Gazur, B. (2010). Blocked dihydropteridines as nitric oxide synthase activators. Pteridines, 20, 27-35.
McInnes, Craig R. ; Suckling, C.J. ; Gibson, C.L. ; Morthala, Raghavendar R. ; Daff, Simon ; Gazur, Ben. / Blocked dihydropteridines as nitric oxide synthase activators. In: Pteridines. 2010 ; Vol. 20. pp. 27-35.
@article{bb0301aa02254ea18605f9db1da097c6,
title = "Blocked dihydropteridines as nitric oxide synthase activators",
abstract = "It has been shown that 6-acetyl-7,7-dimethyl-5,6,7,8-tetrahydropteridin-4(3H)-one can act as a competent cofactor for the production of nitric oxide by neuronal nitric oxide synthase (nNOS). More information was sought on the structural features that could contribute to strong binding within the enzyme whilst maintaining a fast electron transfer rate. This study was concerned with expansion at the C2-position of the pteridine scaffold. The evidence suggests that expansion at the C2-position had a deleterious effect with respect to Km and as a consequence electron transfer rate. Unexpectedly, several lines of evidence suggested that a methyl substituent on nitrogen at C2 reduced the electron density in the pyrimidine and dihydropterin rings.",
keywords = "dihydropteridines, s nitric oxide, synthase activators, pteridines",
author = "McInnes, {Craig R.} and C.J. Suckling and C.L. Gibson and Morthala, {Raghavendar R.} and Simon Daff and Ben Gazur",
year = "2010",
language = "English",
volume = "20",
pages = "27--35",
journal = "Pteridines",
issn = "0933-4807",
publisher = "International Society of Pteridinology",

}

McInnes, CR, Suckling, CJ, Gibson, CL, Morthala, RR, Daff, S & Gazur, B 2010, 'Blocked dihydropteridines as nitric oxide synthase activators' Pteridines, vol. 20, pp. 27-35.

Blocked dihydropteridines as nitric oxide synthase activators. / McInnes, Craig R.; Suckling, C.J.; Gibson, C.L.; Morthala, Raghavendar R.; Daff, Simon; Gazur, Ben.

In: Pteridines, Vol. 20, 2010, p. 27-35.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Blocked dihydropteridines as nitric oxide synthase activators

AU - McInnes, Craig R.

AU - Suckling, C.J.

AU - Gibson, C.L.

AU - Morthala, Raghavendar R.

AU - Daff, Simon

AU - Gazur, Ben

PY - 2010

Y1 - 2010

N2 - It has been shown that 6-acetyl-7,7-dimethyl-5,6,7,8-tetrahydropteridin-4(3H)-one can act as a competent cofactor for the production of nitric oxide by neuronal nitric oxide synthase (nNOS). More information was sought on the structural features that could contribute to strong binding within the enzyme whilst maintaining a fast electron transfer rate. This study was concerned with expansion at the C2-position of the pteridine scaffold. The evidence suggests that expansion at the C2-position had a deleterious effect with respect to Km and as a consequence electron transfer rate. Unexpectedly, several lines of evidence suggested that a methyl substituent on nitrogen at C2 reduced the electron density in the pyrimidine and dihydropterin rings.

AB - It has been shown that 6-acetyl-7,7-dimethyl-5,6,7,8-tetrahydropteridin-4(3H)-one can act as a competent cofactor for the production of nitric oxide by neuronal nitric oxide synthase (nNOS). More information was sought on the structural features that could contribute to strong binding within the enzyme whilst maintaining a fast electron transfer rate. This study was concerned with expansion at the C2-position of the pteridine scaffold. The evidence suggests that expansion at the C2-position had a deleterious effect with respect to Km and as a consequence electron transfer rate. Unexpectedly, several lines of evidence suggested that a methyl substituent on nitrogen at C2 reduced the electron density in the pyrimidine and dihydropterin rings.

KW - dihydropteridines

KW - s nitric oxide

KW - synthase activators

KW - pteridines

UR - http://www.pteridines.org/pteridines.htm

M3 - Article

VL - 20

SP - 27

EP - 35

JO - Pteridines

T2 - Pteridines

JF - Pteridines

SN - 0933-4807

ER -

McInnes CR, Suckling CJ, Gibson CL, Morthala RR, Daff S, Gazur B. Blocked dihydropteridines as nitric oxide synthase activators. Pteridines. 2010;20:27-35.