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Breaking the ‘Don’t Eat Me’ Signal: In Silico Design of CD47 Directed Peptides for Cancer Immunotherapy
  • Masilamani Sobhia,
  • Kapil Laddha
Masilamani Sobhia
National Institute of Pharmaceutical Education and Research

Corresponding Author:[email protected]

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Kapil Laddha
National Institute of Pharmaceutical Education and Research
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Abstract

The main cause of mortality globally is cancer and despite there being a number of therapies available to treat cancer, the success in finding one is like finding a needle in haystack. Immunotherapy emerges to be the one of the needles in this haystack of cancer treatment. Immunotherapeutic agents enhance the immune response of patient’s body to tumor cells One of the immunotherapeutic targets, Cluster of Differentiation 47 (CD47), releases the “don’t eat me” signal when it binds to its receptor, Signal Regulatory Protein (SIRPα). Tumour cells use this signal to circumvent the immune system, rendering it ineffective. In order to stop tumour cells from releasing the “don’t eat me” signal, the CD47-SIRPα interaction is specifically targeted in this study. In order to do so, in silico peptides were designed based on the structural analysis of the interaction between two proteins using point mutations on the interacting residues with the other amino acids. The peptide library was designed and docked on SIRPα using computational tools. Later on, after analysing the docked complex, best of them were selected for MD simulation studies of 100 nanoseconds. Peptides were further analysed after MD studies to narrow down to the possible potential anti-SIRPα peptides.