RESUMO
This review describes recent developments in the evolutionary process of microarrayed compound screening (microARCS to become a robust and efficient ultra-high-throughput screening technology. Improvements in compound spotting (including new quality-control methods), gel casting and imaging, together with software capable of automatic analysis and deconvolution of images, have helped to streamline the screening process. A variety of screening projects using cell-based and non-cell-based approaches have been successfully concluded using microARCS. Comparison of hits derived from standard microtitre-plate-based screening and from microARCS reveals excellent overlap. Furthermore, there seems to be no bias towards finding compounds within a particular range of logP values, even though compounds are solubilized from a dry state during the course of the assay.
Assuntos
Química Farmacêutica/métodos , Avaliação Pré-Clínica de Medicamentos/métodos , Preparações Farmacêuticas/química , Bioensaio/métodos , Géis , Miniaturização/instrumentação , Miniaturização/métodos , Software , Relação Estrutura-AtividadeRESUMO
Recently we cloned tms1 (a putative dehydrogenase) by complementation of a human tumour-derived mutant p53 induced growth arrest in fission yeast. Microinjection of purified tmsl protein into Xenopus laevis embryos abrogated normal embryo development by causing cleavage retardation or cleavage arrest of injected blastomeres in a concentration dependant manner, whereas injection of specific affinity purified tms1 antiserum showed no significant morphological defects. Microinjection of tms1 protein together with affinity purified tms1 antibody resulted in a significantly reduced number of cleavage arrested embryos.