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J Am Chem Soc ; 135(30): 11032-9, 2013 Jul 31.
Artigo em Inglês | MEDLINE | ID: mdl-23822587

RESUMO

Adhesamine is an organic small molecule that promotes adhesion and growth of cultured human cells by binding selectively to heparan sulfate on the cell surface. The present study combined chemical, physicochemical, and cell biological experiments, using adhesamine and its analogues, to examine the mechanism by which this dumbbell-shaped, non-peptidic molecule induces physiologically relevant cell adhesion. The results suggest that multiple adhesamine molecules cooperatively bind to heparan sulfate and induce its assembly, promoting clustering of heparan sulfate-bound syndecan-4 on the cell surface. A pilot study showed that adhesamine improved the viability and attachment of transplanted cells in mice. Further studies of adhesamine and other small molecules could lead to the design of assembly-inducing molecules for use in cell biology and cell therapy.


Assuntos
Heparitina Sulfato/metabolismo , Piperazinas/química , Piperazinas/farmacologia , Animais , Adesão Celular/efeitos dos fármacos , Linhagem Celular Tumoral , Dimerização , Desenho de Fármacos , Humanos , Masculino , Camundongos , Modelos Moleculares , Piperazinas/metabolismo , Multimerização Proteica/efeitos dos fármacos , Estrutura Quaternária de Proteína , Relação Estrutura-Atividade , Sindecanas/química
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