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Titolo:
POLYDEOXYGUANINE MOTIFS IN A 12-MER PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDE AUGMENT BINDING TO THE V3 LOOP OF HIV-1 GP120 AND POTENCY OF HIV-1 INHIBITION INDEPENDENTLY OF G-TETRAD FORMATION
Autore:
LEDERMAN S; SULLIVAN G; BENIMETSKAYA L; LOWY I; LAND K; KHALED Z; CLEARY AM; YAKUBOV L; STEIN CA;
Indirizzi:
COLUMBIA UNIV COLL PHYS & SURG,DEPT MED,630 W 168TH ST NEW YORK NY 10032 COLUMBIA UNIV,NEW YORK STATE PSYCHIAT INST,HIV CTR NEW YORK NY 10032 NOVOSIBIRSK BIOORGAN CHEM INST NOVOSIBIRSK 630090 RUSSIA
Titolo Testata:
ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT
fascicolo: 4, volume: 6, anno: 1996,
pagine: 281 - 289
SICI:
1087-2906(1996)6:4<281:PMIA1P>2.0.ZU;2-M
Fonte:
ISI
Lingua:
ENG
Soggetto:
IMMUNODEFICIENCY-VIRUS TYPE-1; NEUTRALIZING MONOCLONAL-ANTIBODY; FLOW CYTOMETRIC METHOD; MEDIATED CELL-FUSION; ACTIVITY IN-VITRO; DEXTRAN SULFATE; REVERSE-TRANSCRIPTASE; VIRION BINDING; AGENT INVITRO; CATHEPSIN-G;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Science Citation Index Expanded
Science Citation Index Expanded
Citazioni:
41
Recensione:
Indirizzi per estratti:
Citazione:
S. Lederman et al., "POLYDEOXYGUANINE MOTIFS IN A 12-MER PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDE AUGMENT BINDING TO THE V3 LOOP OF HIV-1 GP120 AND POTENCY OF HIV-1 INHIBITION INDEPENDENTLY OF G-TETRAD FORMATION", ANTISENSE & NUCLEIC ACID DRUG DEVELOPMENT, 6(4), 1996, pp. 281-289

Abstract

Phosphorothioate oligodeoxynucleotides belong to a class of polyanions that bind to the third variable domain (v3) of HIV-1 gp120 and inhibit infectivity of a wide variety of HIV-1 isolates. This potent v3 binding of phosphorothioate oligodeoxynucleotides, which is relatively independent of the nucleotide sequence of the oligodeoxynucleotides, decreases with chain length (below 18-mers) and is low for 8-mers, However, recent studies have observed a nucleotide sequence-dependent augmentation of phosphorothioate oligodeoxynucleotide binding to v3 for 8-mers that contain the S-dG(4) moth (e.g., SdT(2)G(4)T(2)) and have suggested that formation of quadruple helical tetraplexes (G-tetrads) is associated with the acquisition of v3 binding ability by small phosphorothioate oligodeoxynucleotides. In the current study, a series of SdG(4)-containing oligodeoxynucleotides were synthesized with varying tandem length (including the 8-mer SdT(2)G(4)T(2), the 12-mer SdG(4)T(4)G(4), and the 28-mer SdG(4)(T(4)G(4))(3)) and compared with phosphorothioate oligodeoxynucleotides (with similar lengths or related sequences) for (1) their inhibition of the binding of mAb 9284, which binds to the N-terminal portion of the v3 loop, (2) the values K-c when these compounds are used as competitors of the rgp120-binding of an alkylating phosphodiester oligodeoxynucleotide probe, and (3) inhibition of HIV-1infectivity in a cell-cell transmission model, The presence of S-dG(4) moths and the number of tandem moths augmented v3 binding and anti-HIV-1 infectivity for small (8-mer or 12-mer oligodeoxynucleotides) butdid not significantly augment the potency of 28-mers, Whereas tetraplex formation of SdT(2)G(4)T(2) may contribute to its v3 binding, the 12-mer SdG(4)T(4)G(4) does not migrate as a tetraplex on nonreducing gels, suggesting that S-dG(4) moths may augment anti-HIV activity by multiple mechanisms.

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Documento generato il 27/11/20 alle ore 11:56:23