Affiliation:
1. Department of Medical Biotechnology, Faculty of Allied Medicine Iran University of Medical Sciences Tehran Iran
2. Department of Biophysics, Faculty of Biological Sciences Tarbiat Modares University Tehran Iran
3. Peptide Chemistry Research Institute, K. N. Toosi University of Technology Tehran Iran
4. Department of Chemistry K. N. Toosi University of Technology Tehran Iran
5. Department of Pharmacology, Department of Biochemistry & Molecular Biology Pennsylvania State University College of Medicine Hershey Pennsylvania USA
Abstract
AbstractCell invasion is an important process in cancer progression and recurrence. Invasion and implantation of cancer cells from their original place to other tissues, by disabling vital organs, challenges the treatment of cancer patients. Given the importance of the matter, many molecular treatments have been developed to inhibit cancer cell invasion. Because of their low production cost and ease of production, peptides are valuable therapeutic molecules for inhibiting cancer cell invasion. In recent years, advances in the field of computational biology have facilitated the design of anti‐cancer peptides. In our investigation, using computational biology approaches such as evolutionary analysis, residue scanning, protein–peptide interaction analysis, molecular dynamics, and free energy analysis, our team designed a peptide library with about 100 000 candidates based on A6 (acetyl‐KPSSPPEE‐amino) sequence which is an anti‐invasion peptide. During computational studies, two of the designed peptides that give the highest scores and showed the greatest sequence similarity to A6 were entered into the experimental analysis workflow for further analysis. In experimental analysis steps, the anti‐metastatic potency and other therapeutic effects of designed peptides were evaluated using MTT assay, RT‐qPCR, zymography analysis, and invasion assay. Our study disclosed that the IK1 (acetyl‐RPSFPPEE‐amino) peptide, like A6, has great potency to inhibit the invasion of cancer cells.
Funder
Iran University of Medical Sciences
Subject
Molecular Biology,Biochemistry,Structural Biology