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İntegrin İnhibitör Cyclo (Arg-Gly-Asp-D-Phe-Val) Peptidinin Moleküler Yapısı ve Kenetlenme Analizi

Year 2021, Volume 6, Issue 2, 1 - 6, 31.12.2021

Abstract

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.

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.
  • 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.

Molecular Structure And Docking Analysis Of The Integrin Inhibitor Cyclo (Arg-Gly-Asp-D-Phe-Val) Peptide

Year 2021, Volume 6, Issue 2, 1 - 6, 31.12.2021

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.

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.
  • 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.

Details

Primary Language English
Subjects Engineering
Journal Section Research Article
Authors

Sefa ÇELİK
İSTANBUL ÜNİVERSİTESİ, FEN FAKÜLTESİ
0000-0001-6216-1297
Türkiye


A. Demet DEMİRAG (Primary Author)
YEDITEPE UNIVERSITY
0000-0002-9609-9150
Türkiye


Hira CİVELEK This is me
YEDİTEPE ÜNİVERSİTESİ, MESLEK YÜKSEKOKULU
0000-0002-4118-5334
Türkiye


Ayşen ÖZEL
İSTANBUL ÜNİVERSİTESİ, FEN FAKÜLTESİ
0000-0002-8680-8830
Türkiye


Sevim AKYÜZ
İSTANBUL KÜLTÜR ÜNİVERSİTESİ, FEN-EDEBİYAT FAKÜLTESİ
0000-0003-3313-6927
Türkiye

Supporting Institution IOCENS Gümüşhane University International Online Conference on ENGINEERING and NATURAL SCIENCES
Publication Date December 31, 2021
Published in Issue Year 2021, Volume 6, Issue 2

Cite

Bibtex @research article { ojn1005271, journal = {Open Journal of Nano}, issn = {}, eissn = {2147-0081}, address = {Sakarya Üniversitesi Fatih Mah. Eşit Sok. No:7/A -11 54580 - Arifiye / SAKARYA}, publisher = {Mustafa CAN}, year = {2021}, volume = {6}, pages = {1 - 6}, doi = {}, title = {Molecular Structure And Docking Analysis Of The Integrin Inhibitor Cyclo (Arg-Gly-Asp-D-Phe-Val) Peptide}, key = {cite}, author = {Çelik, Sefa and Demirag, A. Demet and Civelek, Hira and Özel, Ayşen and Akyüz, Sevim} }
APA Çelik, S. , Demirag, A. D. , Civelek, H. , Özel, A. & Akyüz, S. (2021). Molecular Structure And Docking Analysis Of The Integrin Inhibitor Cyclo (Arg-Gly-Asp-D-Phe-Val) Peptide . Open Journal of Nano , 6 (2) , 1-6 . Retrieved from https://dergipark.org.tr/en/pub/ojn/issue/65078/1005271
MLA Çelik, S. , Demirag, A. D. , Civelek, H. , Özel, A. , Akyüz, S. "Molecular Structure And Docking Analysis Of The Integrin Inhibitor Cyclo (Arg-Gly-Asp-D-Phe-Val) Peptide" . Open Journal of Nano 6 (2021 ): 1-6 <https://dergipark.org.tr/en/pub/ojn/issue/65078/1005271>
Chicago Çelik, S. , Demirag, A. D. , Civelek, H. , Özel, A. , Akyüz, S. "Molecular Structure And Docking Analysis Of The Integrin Inhibitor Cyclo (Arg-Gly-Asp-D-Phe-Val) Peptide". Open Journal of Nano 6 (2021 ): 1-6
RIS TY - JOUR T1 - Molecular Structure And Docking Analysis Of The Integrin Inhibitor Cyclo (Arg-Gly-Asp-D-Phe-Val) Peptide AU - Sefa Çelik , A. Demet Demirag , Hira Civelek , Ayşen Özel , Sevim Akyüz Y1 - 2021 PY - 2021 N1 - DO - T2 - Open Journal of Nano JF - Journal JO - JOR SP - 1 EP - 6 VL - 6 IS - 2 SN - -2147-0081 M3 - UR - Y2 - 2021 ER -
EndNote %0 Open Journal of Nano Molecular Structure And Docking Analysis Of The Integrin Inhibitor Cyclo (Arg-Gly-Asp-D-Phe-Val) Peptide %A Sefa Çelik , A. Demet Demirag , Hira Civelek , Ayşen Özel , Sevim Akyüz %T Molecular Structure And Docking Analysis Of The Integrin Inhibitor Cyclo (Arg-Gly-Asp-D-Phe-Val) Peptide %D 2021 %J Open Journal of Nano %P -2147-0081 %V 6 %N 2 %R %U
ISNAD Çelik, Sefa , Demirag, A. Demet , Civelek, Hira , Özel, Ayşen , Akyüz, Sevim . "Molecular Structure And Docking Analysis Of The Integrin Inhibitor Cyclo (Arg-Gly-Asp-D-Phe-Val) Peptide". Open Journal of Nano 6 / 2 (December 2021): 1-6 .
AMA Çelik S. , Demirag A. D. , Civelek H. , Özel A. , Akyüz S. Molecular Structure And Docking Analysis Of The Integrin Inhibitor Cyclo (Arg-Gly-Asp-D-Phe-Val) Peptide. ojn. 2021; 6(2): 1-6.
Vancouver Çelik S. , Demirag A. D. , Civelek H. , Özel A. , Akyüz S. Molecular Structure And Docking Analysis Of The Integrin Inhibitor Cyclo (Arg-Gly-Asp-D-Phe-Val) Peptide. Open Journal of Nano. 2021; 6(2): 1-6.
IEEE S. Çelik , A. D. Demirag , H. Civelek , A. Özel and S. Akyüz , "Molecular Structure And Docking Analysis Of The Integrin Inhibitor Cyclo (Arg-Gly-Asp-D-Phe-Val) Peptide", Open Journal of Nano, vol. 6, no. 2, pp. 1-6, Dec. 2021

ISSN:2147-0081
The Open Journal of Nano is licensed under a Attribution-NonCommercial 3.0 Unported (CC BY-NC 3.0)