Linked Life Data

12959323

Source:http://linkedlifedata.com/resource/pubmed/id/12959323

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
3
pubmed:dateCreated
2003-9-8
pubmed:abstractText
Monocyte-derived macrophages (M/M) are considered important in vivo reservoirs for different kinds of viruses, including HIV. Hence, therapeutic strategies are urgently needed to protect these cells from virus infection or to control viral replication. In this paper, we report the synthesis, target delivery and in vitro efficacy of a new heterodinucleotide (AZTpPMPA), able to inhibit HIV-1 production in human macrophages. AZTpPMPA consists of two established anti-HIV drugs [zidovudine (AZT) and tenofovir (PMPA)] chemically coupled together by a phosphate bridge. This drug is not able to prevent p24 production when administered for 18 h to M/M experimentally infected with HIV-1 Bal (inhibition 27%), but can almost completely suppress virus production when given encapsulated into autologous erythrocytes (inhibition of p24 production 97%). AZTpPMPA is slowly converted to PMPA, AZT monophosphate and AZT (36 h half-life at 37 degrees C) by cell-resident enzymes. Thus AZTpPMPA should be considered a new prodrug of AZT and PMPA that is able to provide stechiometric amounts of both nucleoside analogues to macrophage cells and to overcome the low phosphorylating activity of M/M for AZT and the modest permeability of PMPA.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
0956-3202
pubmed:author
pubmed:issnType
Print
pubmed:volume
12
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
151-9
pubmed:dateRevised
2007-11-15
pubmed:meshHeading
pubmed:year
2001
pubmed:articleTitle
Inhibition of HIV-1 replication in macrophages by red blood cell-mediated delivery of a heterodinucleotide of azidothymidine and 9-(R)-2-(phosphono methoxypropyl)adenine.
pubmed:affiliation
Dipartimento di Scienze Chimiche, Università di Camerino, 62032 Camerino, Italy. frapa@camserv.unicam.it
pubmed:publicationType
Journal Article, In Vitro, Research Support, Non-U.S. Gov't