Molecular Structure And Docking Analysis Of The Integrin Inhibitor Cyclo (Arg-Gly-Asp-D-Phe-Val) Peptide
Abstract
All possible conformations of Cyclo (Arg-Gly-Asp-D-Phe-Val) (C26H38N8O7) with antitumor activity were determined and the most stable conformer elucidated by MMFF method using the Spartan06 program. The differences in energy between the conformers were determined, and the low energy conformers, which are required for determination of the biological activity, were characterized. Since as an anticancer candidate, the investigated molecule is expected to be an integrin inhibitor, a molecular docking study was conducted with αvβ3 integrin to determine the mechanism of interaction. As a result of docking simulations, the binding affinity ( ΔG = -10.5 kcal/mol) and the interactions between the investigated peptide and target integrin were determined.
Keywords
Antitumor activity, Spartan06 program, Integrin inhibitor, Docking simulation
Supporting Institution
IOCENS Gümüşhane University International Online Conference on ENGINEERING and NATURAL SCIENCES
References
- Referans1 Manninen, A. (2015). Epithelial polarity–generating and integrating signals from the ECM with integrins. Experimental cell research, 334(2), 337-349.
- Referans2 Guan, X. (2015). Cancer metastases: challenges and opportunities. Acta pharmaceutica sinica B, 5(5), 402-418.
- Referans3 Kantola, A. (2010). Latent TGF-β binding proteins-3 and-4: transcriptional control and extracellular matrix targeting.
- Referans4 Rege, T. A., & Hagood, J. S. (2006). Thy‐1 as a regulator of cell‐cell and cell‐matrix interactions in axon regeneration, apoptosis, adhesion, migration, cancer, and fibrosis. The FASEB journal, 20(8), 1045-1054.
- Referans5 Sloan, E. K., Pouliot, N., Stanley, K. L., Chia, J., Moseley, J. M., Hards, D. K., & Anderson, R. L. (2006). Tumor-specific expression of αvβ3 integrin promotes spontaneous metastasis of breast cancer to bone. Breast Cancer Research, 8(2), 1-14.
- Referans6 Danhier, F., Le Breton, A., & Préat, V. (2012). RGD-based strategies to target alpha (v) beta (3) integrin in cancer therapy and diagnosis. Molecular pharmaceutics, 9(11), 2961-2973.
- Referans7 Hamidi, H., & Ivaska, J. (2018). Every step of the way: integrins in cancer progression and metastasis. Nature Reviews Cancer, 18(9), 533-548.
- Referans8 Schneider, J. G., Amend, S. R., & Weilbaecher, K. N. (2011). Integrins and bone metastasis: integrating tumor cell and stromal cell interactions. Bone, 48(1), 54-65.
- Referans9 Zhang, C., Long, L., & Shi, C. (2018). Mitochondria‐targeting IR‐780 dye and its derivatives: synthesis, mechanisms of action, and theranostic applications. Advanced Therapeutics, 1(7), 1800069.
- Referans10 Senthil, K., Aranganathan, S., & Nalini, N. (2004). Evidence of oxidative stress in the circulation of ovarian cancer patients. Clinica chimica acta, 339(1-2), 27-32.
