Poster Presentation International Peptide Symposium 2023

Design and rational engineering of a Batroxicidin peptide derivative for anti-cancer therapy (#321)

Malay Ranjan Nayak 1 , Archana Chugh 1
  1. Indian Institute of Technology, Delhi, Hauz Khas,, NEW DELHI, India

Cancer is a global leading cause of death after cardiovascular disease, accounting for one in six deaths. Conventional treatments include chemotherapy, radiotherapy, and surgery. However, cancer cells may develop resistance to these treatments, leading to metastasis. A novel approach using anti-cancer peptides (ACPs) can be an effective tool for cancer treatment. These peptides, consisting of 10-30 amino acids, with an overall positive charge at physiological pH, specifically target these negatively charged cancer cells while sparing neutral healthy cells. Our research focuses on peptides derived from animal toxins rich in basic amino acids like Lysine and Arginine, which have demonstrated antimicrobial properties. In the present study, Batroxicidin isolated from the South American pit viper (Bothrops atrox) has been investigated for its anti-cancer property. Using the full-length Batroxicidin peptide as a template, different variants have been designed and screened using an online anti-cancer database (viz. AntiCP2.0). The best-scoring peptides were selected for molecular dynamics (MD) simulation and umbrella sampling to observe the interaction between the peptides and biological membranes using Gromacs software. We evaluated various parameters, including free energy, partial density, and gel phasic movement of lipids during peptide penetration through the membranes. Based on the result from the MD simulation, a novel anti-cancer peptide BtxnNC was synthesized. The peptide exhibited cytotoxicity as well as cell-penetrating ability against various cancer cell lines such as MCF7 breast cancer and U87MG glioblastoma in a dose-dependent manner. We are currently assessing the anticancer properties including apoptosis assay and spheroid formation assay. Based on our results, we speculate that this novel peptide may hold a promising anticancer therapeutic strategy.

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