Breaking the ‘Don’t Eat Me’ Signal: In Silico Design of CD47 Directed
Peptides for Cancer Immunotherapy
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.