Human herpesvirus 6 U69 kinase phosphorylates the methylenecyclopropane nucleosides cyclopropavir, MBX 2168, and MBX 1616 to their monophosphates

Gloria Komazin-Meredith; Steven C. Cardinale; John D. Williams; Norton P. Peet; Mark N. Prichard; Terry L. Bowlin

doi:10.1128/AAC.00978-13

Human herpesvirus 6 U69 kinase phosphorylates the methylenecyclopropane nucleosides cyclopropavir, MBX 2168, and MBX 1616 to their monophosphates

Gloria Komazin-Meredith, Steven C. Cardinale, John D. Williams, Norton P. Peet, Mark N. Prichard, Terry L. Bowlin

Biochemistry & Molecular Biology

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Abstract

Dihydroxymethyl and monohydroxymethyl methylenecyclopropane nucleosides are effective inhibitors of both variants of human herpesvirus 6 (HHV-6). We investigated involvement of HHV-6 U69 protein kinase in their mechanism of action. Phosphorylation of the dihydroxymethyl analogue cyclopropavir and monohydroxymethyl nucleosides with either a 6-ether moiety (MBX 2168) or a 6-thioether moiety (MBX 1616) with purified U69 was examined. All three compounds were substrates of this viral kinase and had similar Michaelis-Menten kinetic parameters.

Original language	English (US)
Pages (from-to)	5760-5762
Number of pages	3
Journal	Antimicrobial agents and chemotherapy
Volume	57
Issue number	11
DOIs	https://doi.org/10.1128/AAC.00978-13
State	Published - Nov 2013

All Science Journal Classification (ASJC) codes

Pharmacology
Pharmacology (medical)
Infectious Diseases

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10.1128/AAC.00978-13

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title = "Human herpesvirus 6 U69 kinase phosphorylates the methylenecyclopropane nucleosides cyclopropavir, MBX 2168, and MBX 1616 to their monophosphates",

abstract = "Dihydroxymethyl and monohydroxymethyl methylenecyclopropane nucleosides are effective inhibitors of both variants of human herpesvirus 6 (HHV-6). We investigated involvement of HHV-6 U69 protein kinase in their mechanism of action. Phosphorylation of the dihydroxymethyl analogue cyclopropavir and monohydroxymethyl nucleosides with either a 6-ether moiety (MBX 2168) or a 6-thioether moiety (MBX 1616) with purified U69 was examined. All three compounds were substrates of this viral kinase and had similar Michaelis-Menten kinetic parameters.",

author = "Gloria Komazin-Meredith and Cardinale, {Steven C.} and Williams, {John D.} and Peet, {Norton P.} and Prichard, {Mark N.} and Bowlin, {Terry L.}",

year = "2013",

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doi = "10.1128/AAC.00978-13",

language = "English (US)",

volume = "57",

pages = "5760--5762",

journal = "Antimicrobial agents and chemotherapy",

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publisher = "American Society for Microbiology",

number = "11",

}

Human herpesvirus 6 U69 kinase phosphorylates the methylenecyclopropane nucleosides cyclopropavir, MBX 2168, and MBX 1616 to their monophosphates. / Komazin-Meredith, Gloria; Cardinale, Steven C.; Williams, John D. et al.
In: Antimicrobial agents and chemotherapy, Vol. 57, No. 11, 11.2013, p. 5760-5762.

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

TY - JOUR

T1 - Human herpesvirus 6 U69 kinase phosphorylates the methylenecyclopropane nucleosides cyclopropavir, MBX 2168, and MBX 1616 to their monophosphates

AU - Komazin-Meredith, Gloria

AU - Cardinale, Steven C.

AU - Williams, John D.

AU - Peet, Norton P.

AU - Prichard, Mark N.

AU - Bowlin, Terry L.

PY - 2013/11

Y1 - 2013/11

N2 - Dihydroxymethyl and monohydroxymethyl methylenecyclopropane nucleosides are effective inhibitors of both variants of human herpesvirus 6 (HHV-6). We investigated involvement of HHV-6 U69 protein kinase in their mechanism of action. Phosphorylation of the dihydroxymethyl analogue cyclopropavir and monohydroxymethyl nucleosides with either a 6-ether moiety (MBX 2168) or a 6-thioether moiety (MBX 1616) with purified U69 was examined. All three compounds were substrates of this viral kinase and had similar Michaelis-Menten kinetic parameters.

AB - Dihydroxymethyl and monohydroxymethyl methylenecyclopropane nucleosides are effective inhibitors of both variants of human herpesvirus 6 (HHV-6). We investigated involvement of HHV-6 U69 protein kinase in their mechanism of action. Phosphorylation of the dihydroxymethyl analogue cyclopropavir and monohydroxymethyl nucleosides with either a 6-ether moiety (MBX 2168) or a 6-thioether moiety (MBX 1616) with purified U69 was examined. All three compounds were substrates of this viral kinase and had similar Michaelis-Menten kinetic parameters.

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JO - Antimicrobial agents and chemotherapy

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Human herpesvirus 6 U69 kinase phosphorylates the methylenecyclopropane nucleosides cyclopropavir, MBX 2168, and MBX 1616 to their monophosphates

Abstract

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