Oligovalent amyloid-binding agents reduce SEVI-mediated enhancement of HIV-1 infection.
J Am Chem Soc
; 134(2): 905-8, 2012 Jan 18.
Article
em En
| MEDLINE
| ID: mdl-22239120
ABSTRACT
This paper evaluates the use of oligovalent amyloid-binding molecules as potential agents that can reduce the enhancement of human immunodeficiency virus-1 (HIV-1) infection in cells by semen-derived enhancer of virus infection (SEVI) fibrils. These naturally occurring amyloid fibrils found in semen have been implicated as mediators that can facilitate the attachment and internalization of HIV-1 virions to immune cells. Molecules that are capable of reducing the role of SEVI in HIV-1 infection may, therefore, represent a novel strategy to reduce the rate of sexual transmission of HIV-1 in humans. Here, we evaluated a set of synthetic, oligovalent derivatives of benzothiazole aniline (BTA, a known amyloid-binding molecule) for their capability to bind cooperatively to aggregated amyloid peptides and to neutralize the effects of SEVI in HIV-1 infection. We demonstrate that these BTA derivatives exhibit a general trend of increased binding to aggregated amyloids as a function of increasing valence number of the oligomer. Importantly, we find that oligomers of BTA show improved capability to reduce SEVI-mediated infection of HIV-1 in cells compared to a BTA monomer, with the pentamer exhibiting a 65-fold improvement in efficacy compared to a previously reported monomeric BTA derivative. These results, thus, support the use of amyloid-targeting molecules as potential supplements for microbicides to curb the spread of HIV-1 through sexual contact.
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Sêmen
/
HIV-1
/
Benzotiazóis
/
Ligação Viral
/
Amiloide
/
Compostos de Anilina
Limite:
Humans
Idioma:
En
Revista:
J Am Chem Soc
Ano de publicação:
2012
Tipo de documento:
Article
País de afiliação:
Estados Unidos