Sökning: onr:"swepub:oai:prod.swepub.kib.ki.se:1949271" >
Mechanism of anti-H...
Mechanism of anti-HIV action of masked alaninyl d4T-MP derivatives
-
Balzarini, J (författare)
-
- Karlsson, A (författare)
- Karolinska Institutet
-
Aquaro, S (författare)
-
visa fler...
-
Perno, CF (författare)
-
Cahard, D (författare)
-
Naesens, L (författare)
-
DeClercq, E (författare)
-
McGuigan, C (författare)
-
visa färre...
-
(creator_code:org_t)
- 1996-07-09
- 1996
- Engelska.
-
Ingår i: Proceedings of the National Academy of Sciences of the United States of America. - : Proceedings of the National Academy of Sciences. - 0027-8424. ; 93:14, s. 7295-7299
- Relaterad länk:
-
http://www.pnas.org/...
-
visa fler...
-
http://kipublication...
-
https://doi.org/10.1...
-
visa färre...
Abstract
Ämnesord
Stäng
- So324 is a 2',3'-dideoxy-2',3'-didehydrothymidine-5'-monophosphate (d4T-MP) prodrug containing at the phosphate moiety a phenyl group and the methylester of alanine linked to the phosphate through a phosphoramidate linkage. So324 has anti-HIV activity in human CEM, MT4, and monocyte/macrophage cells that is superior to that of d4T. In contrast to d4T, So324 is also able to inhibit HIV replication in thymidine kinase-deficient CEM cells. After uptake of So324 by intact human lymphocytes, d4T-MP is released and subsequently converted intracellularly to d4T-TP. In addition, accumulation of substantial amounts of a novel d4T derivative has been found. This d4T metabolite has been characterized as alaninyl d4T-MP. The latter metabolite accumulates at approximately 13- to 200-fold higher levels than d4T-TP depending the experimental conditions. Alaninyl d4T-MP should be considered as an intra- and/or extracellular depot form of d4T and/or d4T-MP. These findings may explain the superior anti-retroviral activity of So324 over d4T in cell culture.
Publikations- och innehållstyp
- ref (ämneskategori)
- art (ämneskategori)
Hitta via bibliotek
Till lärosätets databas