Innovating Works

StapPep

Financiado
Stapled peptide analogues as inhibitors of the CCR4-NOT complex to regulate the...
Stapled peptide analogues as inhibitors of the CCR4-NOT complex to regulate the mRNA degradation RNA has gained significant attention in the past few decades due to its evolutionary role in gene regulations. In the regulation process RNA seldom works as an individual entity rather associated with several protein-protein compl... RNA has gained significant attention in the past few decades due to its evolutionary role in gene regulations. In the regulation process RNA seldom works as an individual entity rather associated with several protein-protein complexes (PPCs) and those complexes play a key role in mRNA maturation. Typically, mRNA undergoes different post-transcriptional modifications and deadenylation is one of those post-transcriptional events in which shortening of the poly(A) tail at the 3’ end of mRNA occurs and it plays a major role in mRNA stability. Deadenylation is often regulated by different PPCs and dysregulation of these complexes severely impaired this process. In fact, in many cancer cells shortening of poly(A) tail has been found due to the non-specific deadenylation event. Therefore, Chemical modulators that can regulate the deadenylation process have immense therapeutic importance. CCR4-NOT is one of the most studied deadenylase complexes which actively participate in the deadenylation process. Several types of mRNA-associated proteins (NOT4, Bam, and Roquin) are known which recruit RNA to the CCR4-NOT complex for deadenylation by interacting with CAF40 through its evolutionary conserved site CAF40 binding motif (CBM) domain. Moreover mRNA-associated proteins and RNA both share the same binding surface of the CAF40 protein. Therefore, blocking the interaction between CAF40 and RNA would serve the inhibitory activity of the CCR4-NOT complex towards the deadenylation process. From crystal structure, it has been found that the CBM domain of Bam protein interacts with the CAF40 protein through its α-helical surface. Here in this proposal, we will design α-helical hydrocarbon stapled peptide analogues of CBM domain to exploit the protein-RNA interaction by regulating the activity of CCR4-NOT complex towards deadenylation process. Several biophysical, computational, and cell-based assays will be utilized to investigate the activity and mechanism of deadenylation process. ver más
31/05/2024
MPG
190K€
Duración del proyecto: 24 meses Fecha Inicio: 2022-05-11
Fecha Fin: 2024-05-31

Línea de financiación: concedida

El organismo HORIZON EUROPE notifico la concesión del proyecto el día 2024-05-31
Línea de financiación objetivo El proyecto se financió a través de la siguiente ayuda:
HORIZON-MSCA-2021-PF-01-01: MSCA Postdoctoral Fellowships 2021
Cerrada hace 3 años
Presupuesto El presupuesto total del proyecto asciende a 190K€
Líder del proyecto
MAXPLANCKGESELLSCHAFT ZUR FORDERUNG DER WISSE... No se ha especificado una descripción o un objeto social para esta compañía.
Perfil tecnológico TRL 4-5