Generation of an LFA-1 antagonist by the transfer of the ICAM-1 immunoregulatory epitope to a small molecule.
Science
; 295(5557): 1086-9, 2002 Feb 08.
Article
em En
| MEDLINE
| ID: mdl-11834839
ABSTRACT
The protein-protein interaction between leukocyte functional antigen-1 (LFA-1) and intercellular adhesion molecule-1 (ICAM-1) is critical to lymphocyte and immune system function. Here, we report on the transfer of the contiguous, nonlinear epitope of ICAM-1, responsible for its association with LFA-1, to a small-molecule framework. These LFA-1 antagonists bound LFA-1, blocked binding of ICAM-1, and inhibited a mixed lymphocyte reaction (MLR) with potency significantly greater than that of cyclosporine A. Furthermore, in comparison to an antibody to LFA-1, they exhibited significant anti-inflammatory effects in vivo. These results demonstrate the utility of small-molecule mimics of nonlinear protein epitopes and the protein epitopes themselves as leads in the identification of novel pharmaceutical agents.
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Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Tiofenos
/
Antígeno-1 Associado à Função Linfocitária
/
Beta-Alanina
/
Molécula 1 de Adesão Intercelular
/
Imunossupressores
Idioma:
En
Revista:
Science
Ano de publicação:
2002
Tipo de documento:
Article
País de afiliação:
Estados Unidos