Molecular Structure And Docking Analysis Of The Integrin Inhibitor Cyclo (Arg-Gly-Asp-D-Phe-Val) Peptide
Öz
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.
Anahtar Kelimeler
Antitumor activity Spartan06 program Integrin inhibitor Docking simulation
Destekleyen Kurum
IOCENS Gümüşhane University International Online Conference on ENGINEERING and NATURAL SCIENCES
Kaynakça
- 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.
- Referans11 Bolton, K. L., Chenevix-Trench, G., Goh, C., Sadetzki, S., Ramus, S. J., Karlan, B. Y., ... & Pharoah, P. D. (2012). Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer. Jama, 307(4), 382-389.
- Referans12. Onda, T., Yoshikawa, H., Yasugi, T., Mishima, M., Nakagawa, S., Yamada, M., ... & Taketani, Y. (1998). Patients with ovarian carcinoma upstaged to stage III after systematic lymphadenctomy have similar survival to Stage I/II patients and superior survival to other Stage III patients. Cancer: Interdisciplinary International Journal of the American Cancer Society, 83(8), 1555-1560.
- Referans13 Mattern, J., Koomägi, R., & Volm, M. (1996). Association of vascular endothelial growth factor expression with intratumoral microvessel density and tumour cell proliferation in human epidermoid lung carcinoma. British journal of cancer, 73(7), 931-934.
- Referans14 Ganguly, K. K., Pal, S., Moulik, S., & Chatterjee, A. (2013). Integrins and metastasis. Cell adhesion & migration, 7(3), 251-261.
- Referans15 Ruoslahti, E. (2000, December). Targeting tumor vasculature with homing peptides from phage display. In Seminars in cancer biology (Vol. 10, No. 6, pp. 435-442). Academic Press.
- Reference16 Taherian, A., Li, X., Liu, Y., & Haas, T. A. (2011). Differences in integrin expression and signaling within human breast cancer cells. BMC cancer, 11(1), 1-15.
- Referans17 Burke, P. A., DeNardo, S. J., Miers, L. A., Lamborn, K. R., Matzku, S., & DeNardo, G. L. (2002). Cilengitide targeting of αvβ3 integrin receptor synergizes with radioimmunotherapy to increase efficacy and apoptosis in breast cancer xenografts. Cancer research, 62(15), 4263-4272.
- Referans18 Shao, Y., Molnar, L. F., Jung, Y., Kussmann, J., Ochsenfeld, C., Brown, S. T., ... & DiStasio Jr, R. A. (2006). Advances in methods and algorithms in a modern quantum chemistry program package. Physical Chemistry Chemical Physics,8(27), 3172-3191.
- Referans19 Halgren, T. A. (1996). Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94. Journal of computational chemistry, 17(5‐6), 490-519.
- Referans20 Jurcik, A.; Bednar, D.; Byska, J.; Marques, S.M.; Furmanova, K.; Daniel, L.;... Pavelka, A. CAVER Analyst 2.0: analysis and visualization of channels and tunnels in protein structures and molecular dynamics trajectories. Bioinformatics 2018, 34, 3586-3588.
- Referans21 Trott, O.; Olson, A.J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading.J. Comput. Chem. 2010,31, 455-461.
- Referans22 Xiong, J. P., Stehle, T., Diefenbach, B., Zhang, R., Dunker, R., Scott, D. L., ... & Arnaout, M. A. (2001). Crystal structure of the extracellular segment of integrin αVβ3. Science, 294(5541), 339-345.
Öz
Antitümör aktiviteye sahip Cyclo (Arg-Gly-Asp-D-Phe-Val) (C26H38N8O7) peptidinin tüm olası konformasyonları Spartan06 programı ve MMFF yöntemi ile hesaplanmış ve en kararlı konformer belirlenmiştir. Konformerler arasındaki enerji farklılıkları belirlenmiş, biyolojik aktivitenin belirlenmesi için gerekli olan düşük enerjili konformerler karakterize edilmiştir. Bir antikanser adayı olarak incelenen molekülün integrin inhibitörü olması beklendiğinden, etkileşim mekanizmasını belirlemek için αvβ3 integrini ile moleküler kenetlenme çalışması yapılmıştır. Kenetlenme simülasyonları sonucunda bağlanma afinitesi ( ΔG = -10.5 kcal/mol) ve incelenen peptit ile hedef integrin arasındaki etkileşimler belirlenmiştir.
Anahtar Kelimeler
Antitümör aktivitesi Spartan06 programı integrin inhibitörü Docking simülasyonu
Kaynakça
- 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.
- Referans11 Bolton, K. L., Chenevix-Trench, G., Goh, C., Sadetzki, S., Ramus, S. J., Karlan, B. Y., ... & Pharoah, P. D. (2012). Association between BRCA1 and BRCA2 mutations and survival in women with invasive epithelial ovarian cancer. Jama, 307(4), 382-389.
- Referans12. Onda, T., Yoshikawa, H., Yasugi, T., Mishima, M., Nakagawa, S., Yamada, M., ... & Taketani, Y. (1998). Patients with ovarian carcinoma upstaged to stage III after systematic lymphadenctomy have similar survival to Stage I/II patients and superior survival to other Stage III patients. Cancer: Interdisciplinary International Journal of the American Cancer Society, 83(8), 1555-1560.
- Referans13 Mattern, J., Koomägi, R., & Volm, M. (1996). Association of vascular endothelial growth factor expression with intratumoral microvessel density and tumour cell proliferation in human epidermoid lung carcinoma. British journal of cancer, 73(7), 931-934.
- Referans14 Ganguly, K. K., Pal, S., Moulik, S., & Chatterjee, A. (2013). Integrins and metastasis. Cell adhesion & migration, 7(3), 251-261.
- Referans15 Ruoslahti, E. (2000, December). Targeting tumor vasculature with homing peptides from phage display. In Seminars in cancer biology (Vol. 10, No. 6, pp. 435-442). Academic Press.
- Reference16 Taherian, A., Li, X., Liu, Y., & Haas, T. A. (2011). Differences in integrin expression and signaling within human breast cancer cells. BMC cancer, 11(1), 1-15.
- Referans17 Burke, P. A., DeNardo, S. J., Miers, L. A., Lamborn, K. R., Matzku, S., & DeNardo, G. L. (2002). Cilengitide targeting of αvβ3 integrin receptor synergizes with radioimmunotherapy to increase efficacy and apoptosis in breast cancer xenografts. Cancer research, 62(15), 4263-4272.
- Referans18 Shao, Y., Molnar, L. F., Jung, Y., Kussmann, J., Ochsenfeld, C., Brown, S. T., ... & DiStasio Jr, R. A. (2006). Advances in methods and algorithms in a modern quantum chemistry program package. Physical Chemistry Chemical Physics,8(27), 3172-3191.
- Referans19 Halgren, T. A. (1996). Merck molecular force field. I. Basis, form, scope, parameterization, and performance of MMFF94. Journal of computational chemistry, 17(5‐6), 490-519.
- Referans20 Jurcik, A.; Bednar, D.; Byska, J.; Marques, S.M.; Furmanova, K.; Daniel, L.;... Pavelka, A. CAVER Analyst 2.0: analysis and visualization of channels and tunnels in protein structures and molecular dynamics trajectories. Bioinformatics 2018, 34, 3586-3588.
- Referans21 Trott, O.; Olson, A.J. AutoDock Vina: Improving the speed and accuracy of docking with a new scoring function, efficient optimization, and multithreading.J. Comput. Chem. 2010,31, 455-461.
- Referans22 Xiong, J. P., Stehle, T., Diefenbach, B., Zhang, R., Dunker, R., Scott, D. L., ... & Arnaout, M. A. (2001). Crystal structure of the extracellular segment of integrin αVβ3. Science, 294(5541), 339-345.
Ayrıntılar
| Birincil Dil | İngilizce |
|---|---|
| Konular | Mühendislik |
| Bölüm | Araştırma Makalesi |
| Yazarlar | |
| Yayımlanma Tarihi | 31 Aralık 2021 |
| Gönderilme Tarihi | 8 Ekim 2021 |
| Yayımlandığı Sayı | Yıl 2021 Cilt: 6 Sayı: 2 |
Kaynak Göster
Open Journal of Nano(OJN), dergisi molekülerden mikro boyuttaki yapılara kadar değişen fiziksel, kimyasal ve biyolojik olaylar ve süreçlerle ilgili (ancak bunlarla sınırlı olmayan) bilgilerle ilgilenir.
The Open Journal of Nano dergisinde yayınlanan tüm yayınlar Atıf-GayriTicari 4.0 Uluslararası (CC BY-NC 4.0) lisansı altında lisanlanmıştır.