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Alzheimer Hastalığı Tedavisinde Etkili Cyclo(Phe-Phe) Dipeptidinin Konformasyon Analizi

Year 2021, Volume 26, Issue 3, 135 - 142, 31.12.2021
https://doi.org/10.53433/yyufbed.941445

Abstract

Cyclo(Phe-Phe) dipeptidi Alzheimer hastalığı tedavisinde etkili bir dipeptitdir. Bu çalışmada Cyclo(Phe-Phe) dipeptidinin 3-Boyutlu yapısı teorik konformasyon analizi (TKA) metodu ile belirlenmiştir. Konformasyon analizinde, Ramachandran haritalarından yararlanılarak ve yan-zincir dihedral açıları (χ) yardımıyla tüm olası konformasyonlar belirlenmiştir. Bu haritalar kullanılarak programa girilen başlangıç dihedral açılarla, konformasyon analizi sonunda hesaplanan dihedral açılar karşılaştırmalı olarak verilerek tablolaştırılmıştır. Hesaplama sonucunda dipeptidin en kararlı beş konformasyonunun toplam enerjileri ve toplam enerjilerine katkı sağlayan van der Waals, elektrostatik, hidrojen bağ ve torsiyon enerjileri ayrı ayrı hesaplanmıştır. Ek olarak, en minimum enerjili konformasyon Gaussian03 programı ile DFT metodu kullanılarak optimize edilmiştir. Belirlenen optimize geometri ile konformasyon analizi sonrasında elde edilen geometri karşılaştırılmıştır.

References

  • Alieva, I. N., Mustafayeva, N. N., & Gojayev, N. M. (2006). Conformational analysis of the N-terminal sequence Met1–Val60 of the tyrosine hydroxylase. Journal of Molecular Structure, 785(1-3), 76-84. doi: 10.1016/j.molstruc.2005.09.026
  • Becke, A. D. (1993). Density-functional thermochemistry, III. The role ofexact exchange.The Journal of chemical Physics, 98(7), 5648–5652. doi: 10.1063/1.464913
  • Borthwick, A. D., & Da Costa, N. C. (2017). 2, 5-diketopiperazines in food and beverages: Taste and bioactivity. Critical reviews in food science and nutrition, 57(4), 718-742. doi: 10.1080/10408398.2014.911142
  • Budesinsky, M., Cisarova, I., Borremans, F., Martins, J. C., & Pauwels, E. (2017). Solid-state structure of cyclic dipeptides: an X-ray and computational study of cis-and trans-diketopiperazines of N-methyl-phenylalanine with the thia-pipecolic acids and thia-prolines. Acta Crystallographica Section B: Structural Science, Crystal Engineering and Materials, 73(6), 1179-1193. doi: 10.1107/S2052520617014731
  • Celik, S.,Ozel, A.E.,Kecel, S.,&Akyuz, S. (2012). Structural and IR and Raman spectral analysis of cyclo(His-Phe) dipeptide. Vibrational Spectroscopy, 61, 54-65. doi:10.1016/j.vibspec.2012.01.014
  • Celik, S., & Kecel-Gunduz, S. (2017). Conformational Analysis of Cyclo (Tyr-Cys) and Cyclo (Phe-Cys) Dipeptides. Süleyman Demirel Üniversitesi Fen Bilimleri Enstitüsü Dergisi, 21(2), 306-310.
  • Cheam, T. C., & Krimm, S. (1984). Vibrational analysis of crystalline diketopiperazine—I. Raman and ir spectra. Spectrochimica Acta Part A: Molecular Spectroscopy, 40(6), 481-501.
  • Corey, R. B. (1938). The crystal structure of diketopiperazine. Journal of the American Chemical Society, 60(7), 1598-1604. doi: 10.1021/ja01274a023
  • Çelik, S., Akyüz, S., & Özel, A.E. (2021). Antimikrobiyal ve Antikanser Aktiviteye Sahip Cyclo (Trp-Trp) Dipeptidinin 3-Boyutlu Moleküler Yapısı. Yüzüncü Yıl Üniversitesi Fen Bilimleri Enstitüsü Dergisi, 26(2), 80-87. doi: 10.53433/yyufbed.908710
  • Degeilh, R., & Marsh, R. E. (1959). A refinement of the crystal structure of diketopiperazine (2, 5-piperazinedione). Acta Crystallographica, 12(12), 1007-1014. doi: 10.1107/S0365110X59002845
  • Demir, L., & Godjaev, N. M. (2002). Conformational Analysis of Pol-Rfamide II (Glu1-Trp2-Leu3-Lys4-Gly5-Arg6-Phe7-NH2) Heptapeptide. Turkish Journal of Chemistry, 26(6), 825-832.
  • Dorset, D. L. (2010). Direct methods and refinement in electron and X-ray crystallography–diketopiperazine revisited. Zeitschrift für Kristallographie International journal for structural, physical and chemical aspects of crystalline materials, 225(2-3), 86-93. doi: 10.1524/zkri.2010.1198
  • Falanga, A., Nigro, E., De Biasi, M. G., Daniele, A., Morelli, G., Galdiero, S., & Scudiero, O. (2017). Cyclic peptides as novel therapeutic microbicides: Engineering of human defensin mimetics. Molecules, 22(7), 1217. doi: 10.3390/molecules22071217
  • Frisch, M. J., Trucks, G. W., Schlegel, H. B., Scuseria, G. E., Robb, M. A., Cheeseman, J. R., Montgomery Jr., J. A., Vreven, T., Kudin, K. N., Burant, J. C., Millam, J. M., Iyengar, S. S., Tomasi, J., Barone, V., Mennucci, B., Cossi, M., Scalmani, G., Rega, N., Petersson, G.A., Nakatsuji, H., Hada, M., Ehara, M., Toyota, K., Fukuda, R., Hasegawa, J., Ishida, M., Nakajima, T., Honda, Y., Kitao, O., Nakai, H., Klene, M., Li, X., Knox, J.E., Hratchian, H.P., Cross, J.B., Bakken, V., Adamo, C., Jaramillo, J., Gomperts, R., Stratmann, R.E., Yazyev, O., Austin, A.J., Cammi, R., Pomelli, C., Ochterski, J.W., Ayala, P.Y., Morokuma, K., Voth, G.A., Salvador, P., Dannenberg, J.J., Zakrzewski, V.G., Dapprich, S., Daniels, A. D., Strain, M. C., Farkas, O., Malick, D. K., Rabuck, A. D., Raghavachari, K., Foresman, J. B., Ortiz, J. V., Cui, Q., Baboul, A. G., Clifford, S., Cioslowski, J., Stefanov, B. B., Liu, G., Liashenko, A., Piskorz, P., Komaromi, I., Martin, R.L., Fox, D. J., Keith, T., Al-Laham, M. A., Peng, C. Y., Nanayakkara, A., Challacombe, M., Gill, P. M. W., Johnson, B., Chen, W., Wong, M. W., Gonzalez, C., & Pople, J. A. (2004) .Gaussian 03, Revision C. 02, Gaussian, Inc., Wallingford CT.
  • Gao JP. 2013 Urethanes and ureas and processes. WO Patent no. 2013142969.
  • Gellerman, G., Hazan, E., Brider, T., Traube, T., Albeck, A., & Shatzmiler, S. (2008). Facile synthesis of orthogonally protected optically pure keto-and diketopiperazine building blocks for combinatorial chemistry. International Journal of Peptide Research and Therapeutics, 14(2), 183-192. doi: 10.1007/s10989-008-9129-0
  • Graz, C. J. M., Grant, G. D., Brauns, S. C., Hunt, A., Jamie, H., & Milne, P. J. (2000). Cyclic dipeptides in the induction of maturation for cancer therapy. Journal of pharmacy and pharmacology, 52(1), 75-82. doi: 10.1211/0022357001773535
  • Kaur, K., Kaur, S., & Kapoor, V. K. (2020). Chemical synthesis and anti-inflammatory investigations of some cyclic peptide derivatives. Plant Archives, 20(2), 3531-3540.
  • Kelley, E. W., Norman, S. G., & Scheerer, J. R. (2017). Synthesis of monoalkylidene diketopiperazines and application to the synthesis of barettin. Organic & biomolecular chemistry, 15(40), 8634-8640. doi: 10.1039/C7OB02297B
  • Maksumov, I. S., Ismailova, L. I., &Godjaev, N. M. (1983). The program for semiempirical calculation of conformations of the molecular complexes. J. Struc. Chem.(in Russian), 24, 147.
  • Mendham, A. P., Dines, T. J., Snowden, M. J., Chowdhry, B. Z., & Withnall, R. (2009). Vibrational spectroscopy and DFT calculations of di‐amino acid cyclic peptides. Part I: cyclo (Gly‐Gly), cyclo (L‐Ala‐L‐Ala) and cyclo (L‐Ala‐Gly) in the solid state and in aqueous solution. Journal of Raman Spectroscopy, 40(11), 1478-1497.
  • Mills, I., Cvitas, T., Homann, K., Kallay, N., & Kuchitsu, K. (1988). IUPAC-IUB Quantity. Units and Symbols in Physical Chemistry. Oxford, UK: Blackwell Scientific Publications.
  • Popov, E. M. (1985). An approach to the problem of the structuro-functional organization of natural peptides. Molekuliarnaia biologiia ,19(4), 1107-1138.
  • Popov, E. M. (1979). Quantitative approach to conformations of proteins. International Journal of Quantum Chemistry, 16(4), 707-737. doi:10.1002/qua.560160403
  • Rahman, A. (2019). Studies in Natural Products Chemistry. Amsterdam: Elsevier.
  • Sun, M., Chen, X., Li, W., Lu, C., & Shen, Y. (2017). New diketopiperazine derivatives with cytotoxicity from Nocardiopsis sp. YIM M13066. The Journal of antibiotics, 70(6), 795-797. doi: 10.1038/ja.2017.46
  • Tsuruoka, N., Beppu, Y., Koda, H., Doe, N., Watanabe, H., & Abe, K. (2012). A DKP cyclo (L-Phe-L-Phe) found in chicken essence is a dual inhibitor of the serotonin transporter and acetylcholinesterase. PLoS One, 7(11), e50824. doi: 10.1371/journal.pone.0050824
  • Walchshofer, N., Sarciron, M. E., Garnier, F., Delatour, P., Petavy, A. F., & Paris, J. (1997). Anthelmintic activity of 3, 6-dibenzyl-2, 5-dioxopiperazine, cyclo (L-Phe-L-Phe). Amino Acids, 12(1), 41-47. doi: 10.1007/BF01373425
  • Zhang, D., & Wang, W. (2018). A facile synthesis of cysteine-based diketopiperazine from thiol-protected precursor. Royal Society open science, 5(6), 180272. doi: 10.1098/rsos.180272

Conformational Analysis of Cyclo (Phe-Phe) Dipeptide Effective in the Treatment of Alzheimer's Disease

Year 2021, Volume 26, Issue 3, 135 - 142, 31.12.2021
https://doi.org/10.53433/yyufbed.941445

Abstract

Cyclo (Phe-Phe) dipeptide is an effective dipeptide in the treatment of Alzheimer's disease. In this study, the 3-dimensional structure of the Cyclo (Phe-Phe) dipeptide was determined using the theoretical conformation analysis method. All possible conformations were calculated by conformation analysis, using Ramachandran maps and with the aid of side-chain dihedral angles (χ). By using these maps, the initial dihedral angles entered into the program and the dihedral angles calculated as a result of conformational analysis are given comparatively and tabulated. As a result of the calculation, the total energies of the five most stable conformations of the dipeptide and van der Waals, electrostatic, hydrogen and torsion energies contributing to the total energies were calculated separately. In addition, the lowest energy conformation was optimized by using DFT method with Gaussian03 program. The determined optimized geometry was compared with the geometry obtained after conformational analysis.

References

  • Alieva, I. N., Mustafayeva, N. N., & Gojayev, N. M. (2006). Conformational analysis of the N-terminal sequence Met1–Val60 of the tyrosine hydroxylase. Journal of Molecular Structure, 785(1-3), 76-84. doi: 10.1016/j.molstruc.2005.09.026
  • Becke, A. D. (1993). Density-functional thermochemistry, III. The role ofexact exchange.The Journal of chemical Physics, 98(7), 5648–5652. doi: 10.1063/1.464913
  • Borthwick, A. D., & Da Costa, N. C. (2017). 2, 5-diketopiperazines in food and beverages: Taste and bioactivity. Critical reviews in food science and nutrition, 57(4), 718-742. doi: 10.1080/10408398.2014.911142
  • Budesinsky, M., Cisarova, I., Borremans, F., Martins, J. C., & Pauwels, E. (2017). Solid-state structure of cyclic dipeptides: an X-ray and computational study of cis-and trans-diketopiperazines of N-methyl-phenylalanine with the thia-pipecolic acids and thia-prolines. Acta Crystallographica Section B: Structural Science, Crystal Engineering and Materials, 73(6), 1179-1193. doi: 10.1107/S2052520617014731
  • Celik, S.,Ozel, A.E.,Kecel, S.,&Akyuz, S. (2012). Structural and IR and Raman spectral analysis of cyclo(His-Phe) dipeptide. Vibrational Spectroscopy, 61, 54-65. doi:10.1016/j.vibspec.2012.01.014
  • Celik, S., & Kecel-Gunduz, S. (2017). Conformational Analysis of Cyclo (Tyr-Cys) and Cyclo (Phe-Cys) Dipeptides. Süleyman Demirel Üniversitesi Fen Bilimleri Enstitüsü Dergisi, 21(2), 306-310.
  • Cheam, T. C., & Krimm, S. (1984). Vibrational analysis of crystalline diketopiperazine—I. Raman and ir spectra. Spectrochimica Acta Part A: Molecular Spectroscopy, 40(6), 481-501.
  • Corey, R. B. (1938). The crystal structure of diketopiperazine. Journal of the American Chemical Society, 60(7), 1598-1604. doi: 10.1021/ja01274a023
  • Çelik, S., Akyüz, S., & Özel, A.E. (2021). Antimikrobiyal ve Antikanser Aktiviteye Sahip Cyclo (Trp-Trp) Dipeptidinin 3-Boyutlu Moleküler Yapısı. Yüzüncü Yıl Üniversitesi Fen Bilimleri Enstitüsü Dergisi, 26(2), 80-87. doi: 10.53433/yyufbed.908710
  • Degeilh, R., & Marsh, R. E. (1959). A refinement of the crystal structure of diketopiperazine (2, 5-piperazinedione). Acta Crystallographica, 12(12), 1007-1014. doi: 10.1107/S0365110X59002845
  • Demir, L., & Godjaev, N. M. (2002). Conformational Analysis of Pol-Rfamide II (Glu1-Trp2-Leu3-Lys4-Gly5-Arg6-Phe7-NH2) Heptapeptide. Turkish Journal of Chemistry, 26(6), 825-832.
  • Dorset, D. L. (2010). Direct methods and refinement in electron and X-ray crystallography–diketopiperazine revisited. Zeitschrift für Kristallographie International journal for structural, physical and chemical aspects of crystalline materials, 225(2-3), 86-93. doi: 10.1524/zkri.2010.1198
  • Falanga, A., Nigro, E., De Biasi, M. G., Daniele, A., Morelli, G., Galdiero, S., & Scudiero, O. (2017). Cyclic peptides as novel therapeutic microbicides: Engineering of human defensin mimetics. Molecules, 22(7), 1217. doi: 10.3390/molecules22071217
  • Frisch, M. J., Trucks, G. W., Schlegel, H. B., Scuseria, G. E., Robb, M. A., Cheeseman, J. R., Montgomery Jr., J. A., Vreven, T., Kudin, K. N., Burant, J. C., Millam, J. M., Iyengar, S. S., Tomasi, J., Barone, V., Mennucci, B., Cossi, M., Scalmani, G., Rega, N., Petersson, G.A., Nakatsuji, H., Hada, M., Ehara, M., Toyota, K., Fukuda, R., Hasegawa, J., Ishida, M., Nakajima, T., Honda, Y., Kitao, O., Nakai, H., Klene, M., Li, X., Knox, J.E., Hratchian, H.P., Cross, J.B., Bakken, V., Adamo, C., Jaramillo, J., Gomperts, R., Stratmann, R.E., Yazyev, O., Austin, A.J., Cammi, R., Pomelli, C., Ochterski, J.W., Ayala, P.Y., Morokuma, K., Voth, G.A., Salvador, P., Dannenberg, J.J., Zakrzewski, V.G., Dapprich, S., Daniels, A. D., Strain, M. C., Farkas, O., Malick, D. K., Rabuck, A. D., Raghavachari, K., Foresman, J. B., Ortiz, J. V., Cui, Q., Baboul, A. G., Clifford, S., Cioslowski, J., Stefanov, B. B., Liu, G., Liashenko, A., Piskorz, P., Komaromi, I., Martin, R.L., Fox, D. J., Keith, T., Al-Laham, M. A., Peng, C. Y., Nanayakkara, A., Challacombe, M., Gill, P. M. W., Johnson, B., Chen, W., Wong, M. W., Gonzalez, C., & Pople, J. A. (2004) .Gaussian 03, Revision C. 02, Gaussian, Inc., Wallingford CT.
  • Gao JP. 2013 Urethanes and ureas and processes. WO Patent no. 2013142969.
  • Gellerman, G., Hazan, E., Brider, T., Traube, T., Albeck, A., & Shatzmiler, S. (2008). Facile synthesis of orthogonally protected optically pure keto-and diketopiperazine building blocks for combinatorial chemistry. International Journal of Peptide Research and Therapeutics, 14(2), 183-192. doi: 10.1007/s10989-008-9129-0
  • Graz, C. J. M., Grant, G. D., Brauns, S. C., Hunt, A., Jamie, H., & Milne, P. J. (2000). Cyclic dipeptides in the induction of maturation for cancer therapy. Journal of pharmacy and pharmacology, 52(1), 75-82. doi: 10.1211/0022357001773535
  • Kaur, K., Kaur, S., & Kapoor, V. K. (2020). Chemical synthesis and anti-inflammatory investigations of some cyclic peptide derivatives. Plant Archives, 20(2), 3531-3540.
  • Kelley, E. W., Norman, S. G., & Scheerer, J. R. (2017). Synthesis of monoalkylidene diketopiperazines and application to the synthesis of barettin. Organic & biomolecular chemistry, 15(40), 8634-8640. doi: 10.1039/C7OB02297B
  • Maksumov, I. S., Ismailova, L. I., &Godjaev, N. M. (1983). The program for semiempirical calculation of conformations of the molecular complexes. J. Struc. Chem.(in Russian), 24, 147.
  • Mendham, A. P., Dines, T. J., Snowden, M. J., Chowdhry, B. Z., & Withnall, R. (2009). Vibrational spectroscopy and DFT calculations of di‐amino acid cyclic peptides. Part I: cyclo (Gly‐Gly), cyclo (L‐Ala‐L‐Ala) and cyclo (L‐Ala‐Gly) in the solid state and in aqueous solution. Journal of Raman Spectroscopy, 40(11), 1478-1497.
  • Mills, I., Cvitas, T., Homann, K., Kallay, N., & Kuchitsu, K. (1988). IUPAC-IUB Quantity. Units and Symbols in Physical Chemistry. Oxford, UK: Blackwell Scientific Publications.
  • Popov, E. M. (1985). An approach to the problem of the structuro-functional organization of natural peptides. Molekuliarnaia biologiia ,19(4), 1107-1138.
  • Popov, E. M. (1979). Quantitative approach to conformations of proteins. International Journal of Quantum Chemistry, 16(4), 707-737. doi:10.1002/qua.560160403
  • Rahman, A. (2019). Studies in Natural Products Chemistry. Amsterdam: Elsevier.
  • Sun, M., Chen, X., Li, W., Lu, C., & Shen, Y. (2017). New diketopiperazine derivatives with cytotoxicity from Nocardiopsis sp. YIM M13066. The Journal of antibiotics, 70(6), 795-797. doi: 10.1038/ja.2017.46
  • Tsuruoka, N., Beppu, Y., Koda, H., Doe, N., Watanabe, H., & Abe, K. (2012). A DKP cyclo (L-Phe-L-Phe) found in chicken essence is a dual inhibitor of the serotonin transporter and acetylcholinesterase. PLoS One, 7(11), e50824. doi: 10.1371/journal.pone.0050824
  • Walchshofer, N., Sarciron, M. E., Garnier, F., Delatour, P., Petavy, A. F., & Paris, J. (1997). Anthelmintic activity of 3, 6-dibenzyl-2, 5-dioxopiperazine, cyclo (L-Phe-L-Phe). Amino Acids, 12(1), 41-47. doi: 10.1007/BF01373425
  • Zhang, D., & Wang, W. (2018). A facile synthesis of cysteine-based diketopiperazine from thiol-protected precursor. Royal Society open science, 5(6), 180272. doi: 10.1098/rsos.180272

Details

Primary Language Turkish
Subjects Engineering
Journal Section Articles
Authors

Sefa ÇELİK> (Primary Author)
İSTANBUL ÜNİVERSİTESİ
0000-0001-6216-1297
Türkiye


Sevim AKYÜZ>
İSTANBUL KÜLTÜR ÜNİVERSİTESİ
0000-0003-3313-6927
Türkiye


Ayşen ÖZEL>
İSTANBUL ÜNİVERSİTESİ
0000-0002-8680-8830
Türkiye

Supporting Institution İstanbul Üniversitesi Bilimsel Araştırma Projeleri Yürütücü Sekreterliği
Project Number ÖNAP-2423
Thanks Bu çalışma, İstanbul Üniversitesi Bilimsel Araştırma Projeleri Yürütücü Sekreterliğinin ÖNAP-2423 numaralı projesi ile desteklenmiştir.
Publication Date December 31, 2021
Submission Date May 23, 2021
Acceptance Date July 3, 2021
Published in Issue Year 2021, Volume 26, Issue 3

Cite

APA Çelik, S. , Akyüz, S. & Özel, A. (2021). Alzheimer Hastalığı Tedavisinde Etkili Cyclo(Phe-Phe) Dipeptidinin Konformasyon Analizi . Yüzüncü Yıl Üniversitesi Fen Bilimleri Enstitüsü Dergisi , 26 (3) , 135-142 . DOI: 10.53433/yyufbed.941445