RESUMO
The integration of the viral DNA into the host genome is one of the essential steps in the HIV replication cycle. This process is mediated by the viral enzyme integrase (IN) and lens epithelium-derived growth factor (LEDGF/p75). LEDGF/p75 has been identified as a crucial cellular co-factor of integration that acts by tethering IN to the cellular chromatin. Recently, circular peptides were identified that bind to the C-terminal domain of IN and disrupt the interaction with LEDGF/p75. Starting from the circular peptides, we identified a short peptidic sequence able to inhibit the LEDGF/p75-IN interaction at low µM concentration through its binding to the IN binding site of LEDGF/p75. This discovery can lead to the synthesis of peptidomimetics with high anti-HIV activity targeting the cellular co-factor LEDGF/p75 and not the viral protein IN.
Assuntos
Infecções por HIV/tratamento farmacológico , HIV/metabolismo , Integrases/metabolismo , Peptídeos e Proteínas de Sinalização Intercelular/metabolismo , Peptídeos/administração & dosagem , Sequência de Aminoácidos , Sítios de Ligação , Cromatina/genética , DNA Viral/efeitos dos fármacos , HIV/patogenicidade , Infecções por HIV/genética , Humanos , Integrases/genética , Peptídeos e Proteínas de Sinalização Intercelular/genética , Peptídeos/química , Ligação Proteica/efeitos dos fármacos , Domínios e Motivos de Interação entre Proteínas/efeitos dos fármacos , Integração Viral/genética , Replicação Viral/efeitos dos fármacosRESUMO
This manuscript describes the use of a novel biochip platform for the rapid analysis/identification of nucleic acids, including DNA and microRNAs, with very high specificity. This approach combines a unique dynamic chemistry approach for nucleic acid testing and analysis developed by DestiNA Genomics with the STMicroelectronics In-Check platform, which comprises two microfluidic optimized and independent PCR reaction chambers, and a sequential microarray area for nucleic acid capture and identification by fluorescence. With its compact bench-top "footprint" requiring only a single technician to operate, the biochip system promises to transform and expand routine clinical diagnostic testing and screening for genetic diseases, cancers, drug toxicology and heart disease, as well as employment in the emerging companion diagnostics market.