Mechanism-based inactivation of thymidylate synthase by 5-(3-fluoropropyn-1-yl)-2'-deoxyuridine 5'-phosphate

Thomas I. Kalman; Zhe Nie; Ashwini Kamat

doi:10.1016/S0960-894X(00)00012-3

Mechanism-based inactivation of thymidylate synthase by 5-(3-fluoropropyn-1-yl)-2'-deoxyuridine 5'-phosphate

Thomas I. Kalman
, Zhe Nie
, Ashwini Kamat

Chemistry

SUNY Buffalo

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

8 Scopus citations

Abstract

5-Fluoropropynyl-2'-deoxyuridine 5'-phosphate (3) was designed as a mechanism-based inactivator of thymidylate synthase (TS). The inhibitor was synthesized from 5-iodo-2'-deoxyuridine and propargyl alcohol by palladium-catalyzed coupling, followed by fluorination and selective phosphorylation. Incubation of TS with 3, in the presence or absence of the CH₂H₄folate cofactor, caused rapid, irreversible inactivation of the enzyme. (C) 2000 Elsevier Science Ltd. All rights reserved.

Original language	English
Pages (from-to)	391-394
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	10
Issue number	4
DOIs	https://doi.org/10.1016/S0960-894X(00)00012-3
State	Published - Feb 21 2000

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title = "Mechanism-based inactivation of thymidylate synthase by 5-(3-fluoropropyn-1-yl)-2'-deoxyuridine 5'-phosphate",

abstract = "5-Fluoropropynyl-2'-deoxyuridine 5'-phosphate (3) was designed as a mechanism-based inactivator of thymidylate synthase (TS). The inhibitor was synthesized from 5-iodo-2'-deoxyuridine and propargyl alcohol by palladium-catalyzed coupling, followed by fluorination and selective phosphorylation. Incubation of TS with 3, in the presence or absence of the CH2H4folate cofactor, caused rapid, irreversible inactivation of the enzyme. (C) 2000 Elsevier Science Ltd. All rights reserved.",

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T1 - Mechanism-based inactivation of thymidylate synthase by 5-(3-fluoropropyn-1-yl)-2'-deoxyuridine 5'-phosphate

AU - Kalman, Thomas I.

AU - Nie, Zhe

AU - Kamat, Ashwini

PY - 2000/2/21

Y1 - 2000/2/21

N2 - 5-Fluoropropynyl-2'-deoxyuridine 5'-phosphate (3) was designed as a mechanism-based inactivator of thymidylate synthase (TS). The inhibitor was synthesized from 5-iodo-2'-deoxyuridine and propargyl alcohol by palladium-catalyzed coupling, followed by fluorination and selective phosphorylation. Incubation of TS with 3, in the presence or absence of the CH2H4folate cofactor, caused rapid, irreversible inactivation of the enzyme. (C) 2000 Elsevier Science Ltd. All rights reserved.

AB - 5-Fluoropropynyl-2'-deoxyuridine 5'-phosphate (3) was designed as a mechanism-based inactivator of thymidylate synthase (TS). The inhibitor was synthesized from 5-iodo-2'-deoxyuridine and propargyl alcohol by palladium-catalyzed coupling, followed by fluorination and selective phosphorylation. Incubation of TS with 3, in the presence or absence of the CH2H4folate cofactor, caused rapid, irreversible inactivation of the enzyme. (C) 2000 Elsevier Science Ltd. All rights reserved.

UR - https://www.scopus.com/pages/publications/0034696298

U2 - 10.1016/S0960-894X(00)00012-3

DO - 10.1016/S0960-894X(00)00012-3

M3 - Article

C2 - 10714507

AN - SCOPUS:0034696298

SN - 0960-894X

VL - 10

SP - 391

EP - 394

JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 4

ER -

Mechanism-based inactivation of thymidylate synthase by 5-(3-fluoropropyn-1-yl)-2'-deoxyuridine 5'-phosphate

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