Short Fragmented Peptides from Pardachirus Marmoratus Exhibit Stronger Anticancer Activities in In Silico Residue Replacement and Analyses

• Published in: Current drug discovery technologies Vol. 21; no. 6; p. e220224227304
• Main Authors: Wong, Yong Hui, Lee, Sau Har
• Format: Journal Article
• Language: English
• Published: United Arab Emirates 2024
• Subjects: Animals; Antineoplastic Agents - chemistry; Antineoplastic Agents - pharmacology; Cell Line, Tumor; Computer Simulation; Hemolysis - drug effects; Humans; Molecular Docking Simulation; Neoplasms - drug therapy; Peptide Fragments - chemistry; Peptide Fragments - pharmacology; Peptides - chemistry; Peptides - pharmacology; marine-derived peptide; pardaxin; peptide design; In silico; anticancer peptide; pardachirus marmoratus; peptide length
• ISSN: 1875-6220
• DOI: 10.2174/0115701638290855240207114727

Cancer is a worldwide issue. It has been observed that conventional therapies face many problems, such as side effects and drug resistance. Recent research reportedly used marine-derived products to treat various diseases and explored their potential in treating cancers. This study aims to discover short-length anticancer peptides derived from pardaxin 6 through an approach. Fragmented peptides ranging from 5 to 15 amino acids were derived from the pardaxin 6 parental peptide. These peptides were further replaced with one residue and, along with the original fragmented peptides, were predicted for their SVM scores and physicochemical properties. The top 5 derivative peptides were further examined for their toxicity, hemolytic probability, peptide structures, docking models, and energy scores using various web servers. The trend of analysis outputs across 5 to 15 amino acid fragments was further analyzed. Results showed that when the amino acids were increased, SVM scores of the original fragmented peptides were also increased. Designed peptides had increased SVM scores, which was aligned with previous studies where the single residue replacement transformed the non-anticancer peptide into an anticancer agent. Moreover, studies validated that the designed peptides retained or enhanced anticancer effects against different cancer cell lines. Interestingly, a decreasing trend was observed in those fragmented derivative peptides. Single residue replacement in fragmented pardaxin 6 was found to produce stronger anticancer agents through predictions. Through bioinformatics tools, fragmented peptides improved the efficiency of marine-derived drugs with higher efficacy and lower hemolytic effects in treating cancers.