RESUMO
Despite a deep knowledge on the 3D-structure of several catalytic domains of MMPs, the development of highly specific synthetic active-site-directed inhibitors of MMPs, able to differentiate the different members of this protease family, remains a strong challenge. Due to the flexible nature of MMP active-site, the development of specific MMP inhibitors will need to combine sophisticated theoretical and experimental approaches to decipher in each MMP the specific structural and dynamic features that can be exploited to obtain the desired selectivity.
Assuntos
Desenho de Fármacos , Inibidores de Metaloproteinases de Matriz , Inibidores de Proteases/síntese química , Sequência de Aminoácidos , Sítios de Ligação , Domínio Catalítico , Previsões , Metaloproteinases da Matriz/química , Modelos Moleculares , Dados de Sequência Molecular , Estrutura Molecular , Inibidores de Proteases/química , Inibidores de Proteases/farmacologia , Conformação Proteica , Estrutura Secundária de Proteína , Estrutura Terciária de Proteína , Eletricidade Estática , Zinco/químicaRESUMO
Solid-phase synthesis of phosphinic peptides was introduced 10 years ago. A major application of this chemistry has been the development of potent synthetic inhibitors of zinc metalloproteases. Specific properties of the inhibitors produced in recent years are reviewed, supporting the notion that phosphinic pseudo-peptides are useful tools for studying the structural and functional biology of zinc proteases.