Genotypic and phenotypic characterization of the thymidine kinase of ACV-resistant HSV-1 derived from an acyclovir-sensitive herpes simplex virus type 1 strain1

2002 ◽  
Vol 56 (3) ◽  
pp. 253-262 ◽  
Author(s):  
M SAIJO ◽  
T SUZUTANI ◽  
E DECLERCQ ◽  
M NIIKURA ◽  
A MAEDA ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Thymidine Kinase ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Phenotypic Characterization ◽  
Simplex Virus ◽  
Hsv 1

A new N-methyl thymine derivative comprising a dihydroxyisobutenyl unit as ligand for thymidine kinase of herpes simplex virus type 1 (HSV-1 TK)

2011 ◽  
Vol 21 (20) ◽  
pp. 6161-6165 ◽  
Author(s):  
Svjetlana Krištafor ◽  
Ivana Novaković ◽  
Tatjana Gazivoda Kraljević ◽  
Sandra Kraljević Pavelić ◽  
Pero Lučin ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Thymidine Kinase ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Simplex Virus ◽  
Hsv 1

scholarly journals Kinetic studies with N2-phenylguanines and with l-thymidine indicate that herpes simplex virus type-1 thymidine kinase and thymidylate kinase share a common active site

1994 ◽  
Vol 302 (1) ◽  
pp. 279-282 ◽  
Author(s):  
G Maga ◽  
F Focher ◽  
G E Wright ◽  
M Capobianco ◽  
A Garbesi ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Thymidine Kinase ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Active Site ◽  
Thymidylate Kinase ◽  
Simplex Virus ◽  
Hsv 1

It is known that the Herpes simplex virus type 1 (HSV-1)-encoded thymidine kinase (TK) co-purifies with an associated thymidylate kinase (TMPK) activity and that thymidylate (TMP) inhibits the phosphorylation of thymidine by the HSV-1 TK. Here we demonstrate that: (i) TMP phosphorylation catalysed by the viral TMPK is competitively inhibited by thymidine (TdR) with a Ki equal to its Km as substrate for the viral TK; (ii) L-thymidine (L-TdR), the enantiomer of the naturally occurring D-TdR and a substrate for the HSV-1 TK [Spadari, Maga, Focher, Ciarrocchi, Manservigi, Arcamone, Capobianco, Caruso, Colonna, Iotti and Garbesi (1992) J. Med. Chem. 35, 4214-4220], is a powerful inhibitor of the HSV-1 TMPK activity with a Ki value identical with its Km as a substrate for the viral TK; (iii) both viral TK and TMPK activities are inhibited, in a competitive way and with identical Ki values, by novel, non-substrate inhibitors of HSV-1 TK, N2-phenylguanines; (iv) L-TdR is phosphorylated to L-TMP by the viral TK, but L-TMP is not phosphorylated to L-TDP by the viral TMPK activity; and (v) L-TMP inhibits competitively and with identical potencies the phosphorylation of TdR and TMP catalysed respectively by the HSV-1 TK and TMPK activities. In conclusion, our data demonstrate that both TK and TMPK activities encoded by HSV-1 share a common active site which is very tolerant in accepting modified nucleosides, but cannot readily accommodate modified nucleoside monophosphates.

scholarly journals C-5 Hydroxyethyl and Hydroxypropyl Acyclonucleosides as Substrates for Thymidine Kinase of Herpes Simplex Virus Type 1 (HSV-1 TK): Syntheses and Biological Evaluation

Molecules ◽  
2013 ◽  
Vol 18 (5) ◽  
pp. 5104-5124 ◽  
Author(s):  
Andrijana Meščić ◽  
Svjetlana Krištafor ◽  
Ivana Novaković ◽  
Amar Osmanović ◽  
Ursina Müller ◽  
...  
Keyword(s):  
Herpes Simplex Virus ◽  
Herpes Simplex ◽  
Thymidine Kinase ◽  
Virus Type ◽  
Herpes Simplex Virus Type ◽  
Biological Evaluation ◽  
Simplex Virus ◽  
Hsv 1
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