Exploring structure-activity relationships of transition state analogues of human purine nucleoside phosphorylase

Gary B. Evans, Richard H. Furneaux, Andrzej Lewandowicz, Vern L. Schramm, Peter C. Tyler

Research output: Contribution to journalArticle

74 Citations (Scopus)

Abstract

The aza-C-nucleosides, Immucillin-H and Immucillin-G, are transition state analogue inhibitors of purine nucleoside phosphorylase, a therapeutic target for the control of T-cell proliferation. Immucillin analogues modified at the 2′-, 3′-, or 5′-positions of the azasugar moiety or at the 6-, 7-, or 8-positions of the deazapurine, as well as methylene -bridged analogues, have been synthesized and tested for their inhibition of human purine nucleoside phosphorylase. All analogues were poorer inhibitors, which reflects the superior capture of transition state features in the parent immucillins.

Original languageEnglish (US)
Pages (from-to)3412-3423
Number of pages12
JournalJournal of Medicinal Chemistry
Volume46
Issue number15
DOIs
StatePublished - Jul 17 2003

Fingerprint

Purine-Nucleoside Phosphorylase
Structure-Activity Relationship
T-cells
Cell proliferation
Nucleosides
Cell Proliferation
T-Lymphocytes
Therapeutics
immucillin G
forodesine

ASJC Scopus subject areas

  • Organic Chemistry

Cite this

Exploring structure-activity relationships of transition state analogues of human purine nucleoside phosphorylase. / Evans, Gary B.; Furneaux, Richard H.; Lewandowicz, Andrzej; Schramm, Vern L.; Tyler, Peter C.

In: Journal of Medicinal Chemistry, Vol. 46, No. 15, 17.07.2003, p. 3412-3423.

Research output: Contribution to journalArticle

Evans, Gary B. ; Furneaux, Richard H. ; Lewandowicz, Andrzej ; Schramm, Vern L. ; Tyler, Peter C. / Exploring structure-activity relationships of transition state analogues of human purine nucleoside phosphorylase. In: Journal of Medicinal Chemistry. 2003 ; Vol. 46, No. 15. pp. 3412-3423.
@article{234216e3b66347ec9c19f204001ff3ff,
title = "Exploring structure-activity relationships of transition state analogues of human purine nucleoside phosphorylase",
abstract = "The aza-C-nucleosides, Immucillin-H and Immucillin-G, are transition state analogue inhibitors of purine nucleoside phosphorylase, a therapeutic target for the control of T-cell proliferation. Immucillin analogues modified at the 2′-, 3′-, or 5′-positions of the azasugar moiety or at the 6-, 7-, or 8-positions of the deazapurine, as well as methylene -bridged analogues, have been synthesized and tested for their inhibition of human purine nucleoside phosphorylase. All analogues were poorer inhibitors, which reflects the superior capture of transition state features in the parent immucillins.",
author = "Evans, {Gary B.} and Furneaux, {Richard H.} and Andrzej Lewandowicz and Schramm, {Vern L.} and Tyler, {Peter C.}",
year = "2003",
month = "7",
day = "17",
doi = "10.1021/jm030145r",
language = "English (US)",
volume = "46",
pages = "3412--3423",
journal = "Journal of Medicinal Chemistry",
issn = "0022-2623",
publisher = "American Chemical Society",
number = "15",

}

TY - JOUR

T1 - Exploring structure-activity relationships of transition state analogues of human purine nucleoside phosphorylase

AU - Evans, Gary B.

AU - Furneaux, Richard H.

AU - Lewandowicz, Andrzej

AU - Schramm, Vern L.

AU - Tyler, Peter C.

PY - 2003/7/17

Y1 - 2003/7/17

N2 - The aza-C-nucleosides, Immucillin-H and Immucillin-G, are transition state analogue inhibitors of purine nucleoside phosphorylase, a therapeutic target for the control of T-cell proliferation. Immucillin analogues modified at the 2′-, 3′-, or 5′-positions of the azasugar moiety or at the 6-, 7-, or 8-positions of the deazapurine, as well as methylene -bridged analogues, have been synthesized and tested for their inhibition of human purine nucleoside phosphorylase. All analogues were poorer inhibitors, which reflects the superior capture of transition state features in the parent immucillins.

AB - The aza-C-nucleosides, Immucillin-H and Immucillin-G, are transition state analogue inhibitors of purine nucleoside phosphorylase, a therapeutic target for the control of T-cell proliferation. Immucillin analogues modified at the 2′-, 3′-, or 5′-positions of the azasugar moiety or at the 6-, 7-, or 8-positions of the deazapurine, as well as methylene -bridged analogues, have been synthesized and tested for their inhibition of human purine nucleoside phosphorylase. All analogues were poorer inhibitors, which reflects the superior capture of transition state features in the parent immucillins.

UR - http://www.scopus.com/inward/record.url?scp=0037817418&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0037817418&partnerID=8YFLogxK

U2 - 10.1021/jm030145r

DO - 10.1021/jm030145r

M3 - Article

C2 - 12852771

AN - SCOPUS:0037817418

VL - 46

SP - 3412

EP - 3423

JO - Journal of Medicinal Chemistry

JF - Journal of Medicinal Chemistry

SN - 0022-2623

IS - 15

ER -