Antitumor effects of a peptide sequences based on gramicidin molecule as possible inhibitor of PD-1 and PD-L-1

Abstract: The objective of this study was to evaluate the antitumor effects of peptide sequences based on gramicidin molecule as potential inhibitors of PD-1 and PD-L-1 molecules in computerized and in vitro conditions. In this research, gramicidin sequence was used as the base molecule and its simpler derivatives were designed by adding or subtracting polar amino acids. An ELISA kit was used to prove the involvement of the synthesized peptide in the connection between PD1 and PDL1 molecules. For this, PD1 molecules were first coated in the ELISA wells, and then PDL1 molecules were exposed to them, and the amount of color produced at 630 wavelength was evaluated by enzymatic method. Also, by examining the power of antigenicity, allergenicity, toxicity and homology, only 3 peptides had all the necessary characteristics. In the experimental part, it was clearly determined that by increasing the concentration of the selected peptide up to 42%, the interaction between PD1 and PDL1 is inhibited. Also, the examination of the percentage of death of breast cancer cells (MCF-7) by different concentrations of the selected peptide at 12, 24 and 48 hours showed that the rate of cell death increases with the increase in concentration and time. This study showed that by integrating bioinformatics tests and experimental tests, a suitable peptide can be designed for possible inhibition of PD-1 and PD-L-1 molecules. To check the effectiveness and find out the possible side effects of the selected peptide, additional tests should be done and then it should be tested in an animal model and in a clinical trial.