Design and Characterization of Anticancer Peptides Derived from Snake Venom Metalloproteinase Library

Abstract

Snake venom metalloproteinases (SVMPs) are enzymatic proteins found in snake venom and are known for their diverse biological activities, including induction of hemorrhage and degradation of fibrinogen. This study aimed to design and characterize anticancer peptides (ACPs) derived from an SVMP library based on their physicochemical properties. A comprehensive analysis predicted 185 ACPs and 177 non-ACPs from 652 SVMPs using a SVM algorithm. Among these, only 23 ACPs demonstrated the ability to penetrate cell membranes, of which 5 were selected as promising candidates. A reliable SVM and confidence scores were obtained for all ACP predictions. The predicted ACPs showed optimal hydrophobicity and favorable structural stability in plasma. The predicted ACPs were characterized by low solubility, high rigidity, and high interaction potential based on their net charge, net hydrogen, and steric hindrance. Among the five ACPs, ACP1 (GDLAAIRKRV) and ACP3 (GDETEIRSRI) had unique amino acid compositions, specifically arginine, lysine, aspartic acid, glutamic acid, and α-helical structures. Molecular docking simulations indicated their interactions with various cancer target proteins, leading to inhibit tumor cell proliferation or migration. In conclusion, ACP01 and ACP03 are potential candidates for the future treatment of breast cancer and leukemia.