Investigating the Chemical Reactivity of Kahalalides: A Promising Source of Therapeutic Peptides from Marine Natural Products Using Conceptual Density Functional Theory

Abstract

Marine organisms have been found to produce compounds that have the potential to serve as templates for novel therapeutics. Among these compounds, peptides are of particular interest due to their intermediate size between amino acids and proteins. Kahalalides are a family of structurally complex cyclic peptides with potent cytotoxic and antitumor activities, making them promising candidates for cancer therapy. In this study, we investigate the chemical reactivity of Kahalalides A–F using Conceptual Density Functional Theory to gain insight into their bioactivity from a molecular perspective. Our investigation includes characterizing and isolating the peptides, determining their local and global properties and predicting the active reaction sites. We also calculate Bioactivity Scores to predict their biological targets. Overall, this study contributes to the discovery of new therapeutic peptides from natural sources by providing insights into their chemical reactivity and potential biological targets.