Blocked Dihydropteridines as Nitric Oxide Synthase Activators

Craig R. McInnes; Colin J. Suckling; Colin L. Gibson; Raghavendar R. Morthala; Simon Daff; Ben Gazur

Blocked Dihydropteridines as Nitric Oxide Synthase Activators

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

Research output: Contribution to journal › Article › peer-review

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 K-m 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.

[GRAPHICS]

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Original language	English
Pages (from-to)	27-35
Number of pages	9
Journal	Pteridines
Volume	20
Publication status	Published - Dec 2009

Keywords / Materials (for Non-textual outputs)

ELECTRON-TRANSFER
TETRAHYDROBIOPTERIN

Cite this

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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 K-m 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.[GRAPHICS].",

keywords = "ELECTRON-TRANSFER, TETRAHYDROBIOPTERIN",

author = "McInnes, {Craig R.} and Suckling, {Colin J.} and Gibson, {Colin L.} and Morthala, {Raghavendar R.} and Simon Daff and Ben Gazur",

year = "2009",

month = dec,

language = "English",

volume = "20",

pages = "27--35",

journal = "Pteridines",

issn = "0933-4807",

publisher = "International Society of Pteridinology",

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TY - JOUR

T1 - Blocked Dihydropteridines as Nitric Oxide Synthase Activators

AU - McInnes, Craig R.

AU - Suckling, Colin J.

AU - Gibson, Colin L.

AU - Morthala, Raghavendar R.

AU - Daff, Simon

AU - Gazur, Ben

PY - 2009/12

Y1 - 2009/12

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 K-m 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.[GRAPHICS].

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 K-m 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.[GRAPHICS].

KW - ELECTRON-TRANSFER

KW - TETRAHYDROBIOPTERIN

UR - http://www.scopus.com/inward/record.url?scp=77649098498&partnerID=8YFLogxK

M3 - Article

SN - 0933-4807

VL - 20

SP - 27

EP - 35

JO - Pteridines

JF - Pteridines

ER -

Blocked Dihydropteridines as Nitric Oxide Synthase Activators

Abstract

Keywords / Materials (for Non-textual outputs)

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