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Titolo:
Anti-HIV-1 activity of combinations and covalent conjugates of negatively charged human serum albumins (NCAs) and AZT
Autore:
Kuipers, ME; Swart, PJ; Witvrouw, M; Este, JA; Reymen, D; De Clercq, E; Meijer, DKF;
Indirizzi:
Univ3Groningen, Ctr Pharm, GIDS, Sect Pharmacokinet & Drug Delivery, NL-971 Univ Groningen Groningen Netherlands NL-9713 AV & Drug Delivery, NL-971 Katholieke Univ Leuven, Rega Inst Med Res, Louvain, Belgium Katholieke Univ Leuven Louvain Belgium a Inst Med Res, Louvain, Belgium
Titolo Testata:
JOURNAL OF DRUG TARGETING
fascicolo: 5, volume: 6, anno: 1999,
pagine: 323 - 335
SICI:
1061-186X(1999)6:5<323:AAOCAC>2.0.ZU;2-V
Fonte:
ISI
Lingua:
ENG
Soggetto:
IMMUNODEFICIENCY-VIRUS TYPE-1; ANTI-HIV ACTIVITY; PROTEASE INHIBITORS; REVERSE-TRANSCRIPTASE; SULFATED POLYSACCHARIDES; ENVELOPE GLYCOPROTEIN; SELECTIVE-INHIBITION; MEMBRANE-FUSION; ANTIVIRAL DRUGS; DEXTRAN SULFATE;
Keywords:
Aco-HSA; AZT; HIV; polyanion; Suc-HSA; synergy;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
58
Recensione:
Indirizzi per estratti:
Indirizzo: Swart, PJ Univusroningen, Ctr Pharm, GIDS, Sect Pharmacokinet & Drug Delivery, Antoni Univ Groningen Antonius Deusinglaan 1 Groningen Netherlands NL-9713 AV
Citazione:
M.E. Kuipers et al., "Anti-HIV-1 activity of combinations and covalent conjugates of negatively charged human serum albumins (NCAs) and AZT", J DRUG TAR, 6(5), 1999, pp. 323-335

Abstract

Negatively charged albumins (NCAs, with the prototypes Suc-HSA and Aco-HSA), modified proteins with a potent anti-HIV-1 activity in the nanomolar concentration range, were studied for several aspects of their antiviral mechanism. In addition we investigated the antiviral activity of combinations and covalent conjugates of these NCAs and the reverse transcriptase inhibitorAZT. Addition of NCAs to HIV-l-infected target cells in time-of-addition experiments could be delayed for 30 min after infection before significant loss of activity occurred. Syncytium formation of HIV-infected and uninfected T-cells was inhibited by the NCAs at concentrations of 1-4 mu g/ml. The gp120-mediated virus/cell binding, however, was only inhibited by the NCAs at a 10-fold higher concentrations. The combined data are compatible with a preferential influence on virus/cell fusion. A subsynergistic activity against HIV-I was observed with the non-covalentmixture of Aco-HSA and AZT, When AZT was covalently coupled to the NCAs, and added one hour after infection of the target cells, the anti-HIV-l activity of NCA-AZTMP was diminished by only 2-6-fold, while this was diminishedat least 120-fold for the NCAs, Furthermore the addition of NCA-AZTMP could be delayed up to at least 3h after infection without loss of antiviral activity. It is concluded that AZT that was coupled to the NCAs significantlycontributes to the overall antiviral activity of the conjugates leading tocomplementary effects. These results highlight the potential of using NCA-AZTMP as dual-targetingpreparations against HIV-I in which both the carrier and the coupled drug contribute to the therapeutic efficacy acting at a different level in the replication cycle.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 04/07/20 alle ore 14:59:37