請用此 Handle URI 來引用此文件:
http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/77533
完整後設資料紀錄
DC 欄位 | 值 | 語言 |
---|---|---|
dc.contributor.advisor | 陳平 | |
dc.contributor.author | Chen-Hsu Yu | en |
dc.contributor.author | 余宸旭 | zh_TW |
dc.date.accessioned | 2021-07-10T22:07:22Z | - |
dc.date.available | 2021-07-10T22:07:22Z | - |
dc.date.copyright | 2018-08-14 | |
dc.date.issued | 2018 | |
dc.date.submitted | 2018-08-13 | |
dc.identifier.citation | Chapter1
1. Berg, J. M.; Tymoczko, J. L.; Stryer, L. Biochemistry. W. H. Freeman: 2012. 2. Crick, F. Central dogma of molecular biology. Nature 1970, 227, 561-3. 3. Pauling, L.; Corey, R. B. The planarity of the amide group on polypeptides. J. Am. Chem. Soc. 1952, 74, 3964-3964. 4. Lin, L. N.; Brandts, J. F. Further evidence suggesting that the slow phase in protein unfolding and refolding is due to proline isomerization: a kinetic study of carp parvalbumins. Biochemistry 1978, 17, 4102-10. 5. Baldwin, R. L.; Rose, G. D. Is protein folding hierarchic? I. Local structure and peptide folding. Trends Biochem. Sci. 1999, 24, 26-33. 6. Baldwin, R. L.; Rose, G. D. Is protein folding hierarchic? II. Folding intermediates and transition states. Trends Biochem. Sci. 1999, 24, 77-83. 7. Sanger, F. The terminal peptides of insulin. Biochem. J. 1949, 45, 563-74. 8. Kendrew, J. C.; Bodo, G.; Dintzis, H. M.; Parrish, R. G.; Wyckoff, H.; Phillips, D. C. A three-dimensional model of the myoglobin molecule obtained by X-ray analysis. Nature 1958, 181, 662-6. 9. Perutz, M. F. X-ray analysis of hemoglobin. Science 1963, 140, 863-9. 10. Ramachandran, G. N.; Ramakrishnan, C.; Sasisekharan, V. Stereochemistry of polypeptide chain configurations. J. Mol. Biol. 1963, 7, 95-9. 11. Edsall, J. T.; Flory, P. J.; Kendrew, J. C.; Liquori, A. M.; Nemethy, G.; Ramachandran, G. N.; Scheraga, H. A. A proposal of standard conventions and nomenclature for the description of polypeptide conformation. J. Biol. Chem. 1966, 241, 1004-8. 12. Pauling, L.; Corey, R. B. The pleated sheet, a new layer configuration of polypeptide chains. Proc. Natl. Acad. Sci. U.S.A. 1951, 37, 251-6. 13. Pauling, L.; Corey, R. B.; Branson, H. R. The structure of proteins; two hydrogen-bonded helical configurations of the polypeptide chain. Proc. Natl. Acad. Sci. U.S.A. 1951, 37, 205-11. 14. Toniolo, C.; Bianco, A.; Formaggio, F.; Crisma, M.; Bonora, G. M.; Benedetti, E.; Del Duca, V.; Saviano, M.; Di Blasio, B.; Pedone, C. The polypeptide 310-helix as a template for molecular recognition studies. Structural characterization of a side-chain functionalized octapeptide. Bioorg. Med. Chem. 1995, 3, 1211-21. 15. Adzhubei, A. A.; Sternberg, M. J. Left-handed polyproline II helices commonly occur in globular proteins. J. Mol. Biol. 1993, 229, 472-93. 16. Barlow, D. J.; Thornton, J. M. Helix geometry in proteins. J. Mol. Biol. 1988, 201, 601-19. 17. Arnott, S.; Wonacott, A. J. Atomic co-ordinates for an a-helix: refinement of the crystal structure of alpha-poly-l-alanine. J. Mol. Biol. 1966, 21, 371-83. 18. Hol, W. G.; van Duijnen, P. T.; Berendsen, H. J. The alpha-helix dipole and the properties of proteins. Nature 1978, 273, 443-6. 19. Cowan, P. M.; McGavin, S.; North, A. C. The polypeptide chain configuration of collagen. Nature 1955, 176, 1062-4. 20. Shoulders, M. D.; Raines, R. T. Collagen structure and stability. Annu. Rev. BioChem. 2009, 78, 929-58. 21. Adzhubei, A. A.; Sternberg, M. J.; Makarov, A. A. Polyproline-II helix in proteins: structure and function. J. Mol. Biol. 2013, 425, 2100-32. 22. Mihailescu, M. R.; Russu, I. M. A signature of the T ---> R transition in human hemoglobin. Proc. Natl. Acad. Sci. U.S.A. 2001, 98, 3773-7. 23. Hirs, C. H.; Moore, S.; Stein, W. H. The sequence of the amino acid residues in performic acid-oxidized ribonuclease. J. Biol. Chem. 1960, 235, 633-47. 24. Dill, K. A. Dominant forces in protein folding. Biochemistry 1990, 29, 7133-55. 25. Elcock, A. H. The stability of salt bridges at high temperatures: implications for hyperthermophilic proteins. J. Mol. Biol. 1998, 284, 489-502. 26. Stickle, D. F.; Presta, L. G.; Dill, K. A.; Rose, G. D. Hydrogen bonding in globular proteins. J. Mol. Biol. 1992, 226, 1143-59. 27. Makhatadze, G. I.; Privalov, P. L. Energetics of protein structure. Adv. Protein Chem. 1995, 47, 307-425. 28. Frank, H. S.; Evans, M. W. Free Volume and Entropy in Condensed Systems .3. Entropy in Binary Liquid Mixtures - Partial Molal Entropy in Dilute Solutions - Structure and Thermodynamics in Aqueous Electrolytes. J. Chem. Phys. 1945, 13, 507-532. 29. Silbey, R. J.; Alberty, R. A.; Bawendi, M. G. Physical Chemistry. 4 ed.; John Wiley: 2004. 30. Gitlin, I.; Carbeck, J. D.; Whitesides, G. M. Why are proteins charged? Networks of charge-charge interactions in proteins measured by charge ladders and capillary electrophoresis. Angew Chem. Int. Ed. Engl. 2006, 45, 3022-60. 31. Zhao, N.; Pang, B.; Shyu, C. R.; Korkin, D. Charged residues at protein interaction interfaces: unexpected conservation and orchestrated divergence. Protein Sci. 2011, 20, 1275-84. 32. Harley, C. A.; Tipper, D. J. The role of charged residues in determining transmembrane protein insertion orientation in yeast. J. Biol. Chem. 1996, 271, 24625-33. 33. Cheng, R. P.; Weng, Y. J.; Wang, W. R.; Koyack, M. J.; Suzuki, Y.; Wu, C. H.; Yang, P. A.; Hsu, H. C.; Kuo, H. T.; Girinath, P.; Fang, C. J. Helix formation and capping energetics of arginine analogs with varying side chain length. Amino Acids 2012, 43, 195-206. 34. Kuo, H.-T.; Liu, S.-L.; Chiu, W.-C.; Fang, C.-J.; Chang, H.-C.; Wang, W.-R.; Yang, P.-A.; Li, J.-H.; Huang, S.-J.; Huang, S.-L.; Cheng, R. P. Effect of charged amino acid side chain length on lateral cross-strand interactions between carboxylate- and guanidinium-containing residues in a beta-hairpin. Amino Acids 2015, 47, 885-98. 35. Kuo, H.-T.; Fang, C.-J.; Tsai, H.-Y.; Yang, M.-F.; Chang, H.-C.; Liu, S.-L.; Kuo, L.-H.; Wang, W.-R.; Yang, P.-A.; Huang, S.-J.; Huang, S.-L.; Cheng, R. P. Effect of charged amino acid side chain length on lateral cross-strand interactions between carboxylate-containing residues and lysine analogues in a beta-hairpin. Biochemistry 2013, 52, 9212-22. 36. Kuo, L.-H.; Li, J.-H.; Kuo, H.-T.; Hung, C.-Y.; Tsai, H.-Y.; Chiu, W.-C.; Wu, C.-H.; Wang, W.-R.; Yang, P.-A.; Yao, Y.-C.; Wong, T.-W.; Huang, S.-J.; Huang, S.-L.; Cheng, R. P. Effect of charged amino acid side chain length at non-hydrogen bonded strand positions on beta-hairpin stability. Biochemistry 2013, 52, 7785-97. 37. Chen, C. X.; Hu, J.; Yang, C.; Zhang, Y.; Wang, F.; Mu, Q. M.; Pan, F.; Xu, H.; Lu, J. R. Amino acid side chains affect the bioactivity of designed short peptide amphiphiles. J. Mater. Chem. B 2016, 4, 2359-2368. 38. Wu, C. H.; Chen, Y. P.; Mou, C. Y.; Cheng, R. P. Altering the Tat-derived peptide bioactivity landscape by changing the arginine side chain length. Amino Acids 2013, 44, 473-480. 39. Di Lullo, G. A.; Sweeney, S. M.; Korkko, J.; Ala-Kokko, L.; San Antonio, J. D. Mapping the ligand-binding sites and disease-associated mutations on the most abundant protein in the human, type I collagen. J. Biol. Chem. 2002, 277, 4223-31. 40. Chang, S. W.; Shefelbine, S. J.; Buehler, M. J. Structural and mechanical differences between collagen homo- and heterotrimers: relevance for the molecular origin of brittle bone disease. Biophys. J. 2012, 102, 640-8. 41. Gelse, K.; Poschl, E.; Aigner, T. Collagens--structure, function, and biosynthesis. Adv. Drug Deliv. Rev. 2003, 55, 1531-46. 42. Horton, K. L.; Stewart, K. M.; Fonseca, S. B.; Guo, Q.; Kelley, S. O. Mitochondria-penetrating peptides. Chem. Biol. 2008, 15, 375-82. 43. Yousif, L. F.; Stewart, K. M.; Kelley, S. O. Targeting mitochondria with organelle-specific compounds: strategies and applications. ChemBioChem. 2009, 10, 1939-50. 44. Yousif, L. F.; Stewart, K. M.; Horton, K. L.; Kelley, S. O. Mitochondria-penetrating peptides: sequence effects and model cargo transport. ChemBioChem. 2009, 10, 2081-8. 45. Gelse, K.; Poschl, E.; Aigner, T. Collagens - structure, function, and biosynthesis. Adv. Drug Deliv. Rev. 2003, 55, 1531-1546. 46. Persikov, A. V.; Ramshaw, J. A.; Kirkpatrick, A.; Brodsky, B. Amino acid propensities for the collagen triple-helix. Biochemistry 2000, 39, 14960-14967. Chapter2 1. Hall, A. Rho GTPases and the actin cytoskeleton. Science 1998, 279, 509-514. 2. Anfinsen, C. B. The formation and stabilization of protein structure. Biochem. J. 1972, 128, 737-749. 3. Baldwin, R. L.; Rose, G. D. Is protein folding hierarchic? I. Local structure and peptide folding. Trends Biochem. Sci. 1999, 24, 26-33. 4. Baldwin, R. L.; Rose, G. D. Is protein folding hierarchic? II. Folding intermediates and transition states. Trends Biochem. Sci. 1999, 24, 77-83. 5. Di Lullo, G. A.; Sweeney, S. M.; Korkko, J.; Ala-Kokko, L.; San Antonio, J. D. Mapping the ligand-binding sites and disease-associated mutations on the most abundant protein in the human, type I collagen. J. Biol. Chem. 2002, 277, 4223-4231. 6. Chang, S. W.; Shefelbine, S. J.; Buehler, M. J. Structural and mechanical differences between collagen homo- and heterotrimers: relevance for the molecular origin of brittle bone disease. Biophys. J. 2012, 102, 640-648. 7. Gelse, K.; Poschl, E.; Aigner, T. Collagens - structure, function, and biosynthesis. Adv. Drug Deliv. Rev. 2003, 55, 1531-1546. 8. Buehler, M. J. Nature designs tough collagen: explaining the nanostructure of collagen fibrils. Proc. Natl. Acad. Sci. U. S. A. 2006, 103, 12285-12290. 9. Gauba, V.; Hartgerink, J. D. Self-assembled heterotrimeric collagen triple helices directed through electrostatic interactions. J. Am. Chem. Soc. 2007, 129, 2683-2690. 10. Chan, V. C.; Ramshaw, J. A.; Kirkpatrick, A.; Beck, K.; Brodsky, B. Positional preferences of ionizable residues in Gly-X-Y triplets of the collagen triple-helix. J. Biol. Chem. 1997, 272, 31441-31446. 11. Okuyama, K.; Hongo, C.; Fukushima, R.; Wu, G.; Narita, H.; Noguchi, K.; Tanaka, Y.; Nishino, N. Crystal structures of collagen model peptides with Pro-Hyp-Gly repeating sequence at 1.26 A resolution: implications for proline ring puckering. Biopolymers 2004, 76, 367-77. 12. Shoulders, M. D.; Raines, R. T. Collagen structure and stability. Annu. Rev. Biochem. 2009, 78, 929-958. 13. Hodges, J. A.; Raines, R. T. Stereoelectronic and steric effects in the collagen triple helix: toward a code for strand association. J. Am. Chem. Soc. 2005, 127, 15923-32. 14. Katz, E. P.; David, C. W. Energetics of intrachain salt-linkage formation in collagen. Biopolymers 1990, 29, 791-798. 15. Venugopal, M. G.; Ramshaw, J. A.; Braswell, E.; Zhu, D.; Brodsky, B. Electrostatic interactions in collagen-like triple-helical peptides. Biochemistry 1994, 33, 7948-7956. 16. Bretscher, L. E.; Jenkins, C. L.; Taylor, K. M.; DeRider, M. L.; Raines, R. T. Conformational stability of collagen relies on a stereoelectronic effect. J. Am. Chem. Soc. 2001, 123, 777-778. 17. Gauba, V.; Hartgerink, J. D. Surprisingly high stability of collagen ABC heterotrimer: evaluation of side chain charge pairs. J. Am. Chem. Soc. 2007, 129, 15034-15041. 18. Persikov, A. V.; Ramshaw, J. A.; Kirkpatrick, A.; Brodsky, B. Amino acid propensities for the collagen triple-helix. Biochemistry 2000, 39, 14960-14967. 19. Persikov, A. V.; Ramshaw, J. A.; Kirkpatrick, A.; Brodsky, B. Electrostatic interactions involving lysine make major contributions to collagen triple-helix stability. Biochemistry 2005, 44, 1414-1422. 20. Hall, D. A.; Reed, R. Hydroxyproline and thermal stability of collagen. Nature 1957, 180, 243. 21. Davis, J. M.; Bachinger, H. P. Hysteresis in the triple helix-coil transition of type III collagen. J. Biol. Chem. 1993, 268, 25965-72. 22. Engel, J.; Bachinger, H. P. Cooperative equilibrium transitions coupled with a slow annealing step explain the sharpness and hysteresis of collagen folding. Matrix Biol. 2000, 19, 235-44. 23. Mizuno, K.; Boudko, S. P.; Engel, J.; Bachinger, H. P. Kinetic hysteresis in collagen folding. Biophys. J. 2010, 98, 3004-14. 24. Bachinger, H. P.; Bruckner, P.; Timpl, R.; Prockop, D. J.; Engel, J. Folding mechanism of the triple helix in type-III collagen and type-III pN-collagen. Role of disulfide bridges and peptide bond isomerization. Eur. J. Biochem. 1980, 106, 619-32. 25. Bächinger, H. P.; Engel, J. The Thermodynamics and Kinetics of Collagen Folding. In Protein Folding Handbook, Buchner, J.; Kiefhaber, T., Eds. 2008. 26. Shah, N. K.; Ramshaw, J. A.; Kirkpatrick, A.; Shah, C.; Brodsky, B. A host-guest set of triple-helical peptides: stability of Gly-X-Y triplets containing common nonpolar residues. Biochemistry 1996, 35, 10262-10268. 27. Salem, G.; Traub, W. Conformational implications of amino acid sequence regularities in collagen. FEBS Lett. 1975, 51, 94-9. 28. Emsley, J.; Knight, C. G.; Farndale, R. W.; Barnes, M. J.; Liddington, R. C. Structural basis of collagen recognition by integrin alpha2beta1. Cell 2000, 101, 47-56. 29. Fallas, J. A.; Dong, J.; Tao, Y. J.; Hartgerink, J. D. Structural insights into charge pair interactions in triple helical collagen-like proteins. J. Biol. Chem. 2012, 287, 8039-8047. 30. Cheng, R. P.; Weng, Y.-J.; Wang, W.-R.; Koyack, M. J.; Suzuki, Y.; Wu, C.-H.; Yang, P.-A.; Hsu, H.-C.; Kuo, H.-T.; Girinath, P.; Fang, C.-J. Helix formation and capping energetics of arginine analogs with varying side chain length. Amino Acids 2012, 43, 195-206. 31. Kuo, H.-T.; Fang, C.-J.; Tsai, H.-Y.; Yang, M.-F.; Chang, H.-C.; Liu, S.-L.; Kuo, L.-H.; Wang, W.-R.; Yang, P.-A.; Huang, S.-J.; Huang, S.-L.; Cheng, R. P. Effect of charged amino acid side chain length on lateral cross-strand interactions between carboxylate-containing residues and lysine analogues in a b-hairpin. Biochemistry 2013, 52, 9212-22. 32. Kuo, L.-H.; Li, J.-H.; Kuo, H.-T.; Hung, C.-Y.; Tsai, H.-Y.; Chiu, W.-C.; Wu, C.-H.; Wang, W.-R.; Yang, P.-A.; Yao, Y.-C.; Wong, T.-W.; Huang, S.-J.; Huang, S.-L.; Cheng, R. P. Effect of charged amino acid side chain length at non-hydrogen bonded strand positions on b-hairpin stability. Biochemistry 2013, 52, 7785-97. 33. Kuo, H.-T.; Liu, S.-L.; Chiu, W.-C.; Fang, C.-J.; Chang, H.-C.; Wang, W.-R.; Yang, P.-A.; Li, J.-H.; Huang, S.-J.; Huang, S.-L.; Cheng, R. P. Effect of charged amino acid side chain length on lateral cross-strand interactions between carboxylate- and guanidinium-containing residues in a b-hairpin. Amino Acids 2015, 47, 885-98. 34. Xu, F.; Zahid, S.; Silva, T.; Nanda, V. Computational design of a collagen A:B:C-type heterotrimer. J. Am. Chem. Soc. 2011, 133, 15260-15263. 35. Fallas, J. A.; Hartgerink, J. D. Computational design of self-assembling register-specific collagen heterotrimers. Nat. Commun. 2012, 3, 1087. 36. Jalan, A. A.; Demeler, B.; Hartgerink, J. D. Hydroxyproline-free single composition ABC collagen heterotrimer. J. Am. Chem. Soc. 2013, 135, 6014-6017. 37. Xu, F.; Silva, T.; Joshi, M.; Zahid, S.; Nanda, V. Circular permutation directs orthogonal assembly in complex collagen peptide mixtures. J. Biol. Chem. 2013, 288, 31616-31623. 38. Chakrabartty, A.; Kortemme, T.; Padmanabhan, S.; Baldwin, R. L. Aromatic side-chain contribution to far-ultraviolet circular dichroism of helical peptides and its effect on measurement of helix propensities. Biochemistry 1993, 32, 5560-5. 39. Cheng, R. P.; Girinath, P.; Suzuki, Y.; Kuo, H.-T.; Hsu, H.-C.; Wang, W.-R.; Yang, P.-A.; Gullickson, D.; Wu, C.-H.; Koyack, M. J.; Chiu, H.-P.; Weng, Y.-J.; Hart, P.; Kokona, B.; Fairman, R.; Lin, T.-E.; Barrett, O. Positional effects on helical Ala-based peptides. Biochemistry 2010, 49, 9372-9384. 40. Fields, G. B.; Noble, R. L. Solid phase peptide synthesis utilizing 9-fluorenylmethoxycarbonyl amino acids. Int J Pept Protein Res 1990, 35, 161-214. 41. Wang, W.-M. Effect of arginine side chain length on b-hairpin stability and effect of the number of POG triplets on heterotrimeric collagen triple helix stability and specificity. Master thesis, National Taiwan University, 2017. 42. Bächinger, H. P.; Mizuno, K. Collagen Triple Helix: Stability. In Wiley Encyclopedia of Chemical Biology, T. P. Begley ed.; 2008. 43. Chen, Y.-C. Effect of chargrd amino acid side chain length at the X position or the Y position on collagen triple helix stability. Master thesis, National Taiwan University, 2018. 44. Edelhoch, H. Spectroscopic determination of tryptophan and tyrosine in proteins. Biochemistry 1967, 6, 1948-54. 45. Pace, C. N.; Vajdos, F.; Fee, L.; Grimsley, G.; Gray, T. How to measure and predict the molar absorption coefficient of a protein. Protein Sci. 1995, 4, 2411-2423. Chapter3 1. Voet, D.; Voet;, J. G.; Pratt, C. W. Fundamentals of Biochemistry. 2 ed.; John Wiley and Sons, Inc.: 2006; p 547, 556. 2. McBride, H. M.; Neuspiel, M.; Wasiak, S. Mitochondria: more than just a powerhouse. Curr. Biol. 2006, 16, R551-560. 3. Zeviani, M.; Di Donato, S. Mitochondrial disorders. Brain 2004, 127, 2153-2172. 4. Yousif, L. F.; Stewart, K. M.; Kelley, S. O. Targeting mitochondria with organelle-specific compounds: strategies and applications. ChemBioChem. 2009, 10, 1939-1950. 5. Horton, K. L.; Stewart, K. M.; Fonseca, S. B.; Guo, Q.; Kelley, S. O. Mitochondria-penetrating peptides. Chem. Biol. 2008, 15, 375-82. 6. Alberts, B.; Johnson, A.; Lewis, J.; Raff, M.; Roberts, K.; Walter, P. Molecular Biology of the Cell. 4th ed.; New York: Garland Science: 2002. 7. McMillin, J. B.; Dowhan, W. Cardiolipin and apoptosis. Biochim. Biophys. Acta. 2002, 1585, 97-107. 8. Johnson, L. V.; Walsh, M. L.; Chen, L. B. Localization of mitochondria in living cells with rhodamine 123. Proc. Natl. Acad. Sci. U. S. A. 1980, 77, 990-4. 9. Murphy, M. P. Selective targeting of bioactive compounds to mitochondria. Trends Biotechnol. 1997, 15, 326-30. 10. Ross, M. F.; Kelso, G. F.; Blaikie, F. H.; James, A. M.; Cocheme, H. M.; Filipovska, A.; Da Ros, T.; Hurd, T. R.; Smith, R. A.; Murphy, M. P. Lipophilic triphenylphosphonium cations as tools in mitochondrial bioenergetics and free radical biology. Biochemistry 2005, 70, 222-230. 11. Lithgow, T.; Glick, B. S.; Schatz, G. The protein import receptor of mitochondria. Trends Biochem. Sci. 1995, 20, 98-101. 12. Roise, D.; Schatz, G. Mitochondrial presequences. J. Biol. Chem. 1988, 263, 4509-4511. 13. Omura, T. Mitochondria-targeting sequence, a multi-role sorting sequence recognized at all steps of protein import into mitochondria. J. Biochem. 1998, 123, 1010-1016. 14. Yamada, Y.; Akita, H.; Kamiya, H.; Kogure, K.; Yamamoto, T.; Shinohara, Y.; Yamashita, K.; Kobayashi, H.; Kikuchi, H.; Harashima, H. MITO-Porter: A liposome-based carrier system for delivery of macromolecules into mitochondria via membrane fusion. Biochim. Biophys. Acta. 2008, 1778, 423-432. 15. Weissig, V.; Lasch, J.; Erdos, G.; Meyer, H. W.; Rowe, T. C.; Hughes, J. DQAsomes: a novel potential drug and gene delivery system made from Dequalinium. Pharm. Res. 1998, 15, 334-337. 16. Rin Jean, S.; Tulumello, D. V.; Wisnovsky, S. P.; Lei, E. K.; Pereira, M. P.; Kelley, S. O. Molecular vehicles for mitochondrial chemical biology and drug delivery. ACS Chem. Biol. 2014, 9, 323-333. 17. Ross, M. F.; Filipovska, A.; Smith, R. A.; Gait, M. J.; Murphy, M. P. Cell-penetrating peptides do not cross mitochondrial membranes even when conjugated to a lipophilic cation: evidence against direct passage through phospholipid bilayers. Biochem. J. 2004, 383, 457-468. 18. Marbella, L. E.; Cho, H. S.; Spence, M. M. Observing the translocation of a mitochondria-penetrating peptide with solid-state NMR. Biochim. Biophys. Acta. 2013, 1828, 1674-1682. 19. Schwieger, C.; Blume, A. Interaction of poly(L-arginine) with negatively charged DPPG membranes: calorimetric and monolayer studies. Biomacro. 2009, 10, 2152-2161. 20. Szeto, H. H. Cell-permeable, mitochondrial-targeted, peptide antioxidants. AAPS J. 2006, 8, E277-283. 21. Zhao, K.; Zhao, G. M.; Wu, D.; Soong, Y.; Birk, A. V.; Schiller, P. W.; Szeto, H. H. Cell-permeable peptide antioxidants targeted to inner mitochondrial membrane inhibit mitochondrial swelling, oxidative cell death, and reperfusion injury. J. Biol. Chem. 2004, 279, 34682-34690. 22. Green, M.; Loewenstein, P. M. Autonomous functional domains of chemically synthesized human immunodeficiency virus tat trans-activator protein. Cell 1988, 55, 1179-1188. 23. Derossi, D.; Joliot, A. H.; Chassaing, G.; Prochiantz, A. The third helix of the Antennapedia homeodomain translocates through biological membranes. J. Biol. Chem. 1994, 269, 10444-10450. 24. Horton, K. L.; Pereira, M. P.; Stewart, K. M.; Fonseca, S. B.; Kelley, S. O. Tuning the activity of mitochondria-penetrating peptides for delivery or disruption. Chembiochem. 2012, 13, 476-485. 25. Kelley, S. O.; Stewart, K. M.; Mourtada, R. Development of novel peptides for mitochondrial drug delivery: amino acids featuring delocalized lipophilic cations. Pharm. Res. 2011, 28, 2808-2819. 26. Lei, E. K.; Pereira, M. P.; Kelley, S. O. Tuning the intracellular bacterial targeting of peptidic vectors. Angew. Chem. Int. Ed. Engl. 2013, 52, 9660-9963. 27. Chamberlain, G. R.; Tulumello, D. V.; Kelley, S. O. Targeted delivery of doxorubicin to mitochondria. ACS Chem. Biol. 2013, 8, 1389-1395. 28. Wisnovsky, S. P.; Wilson, J. J.; Radford, R. J.; Pereira, M. P.; Chan, M. R.; Laposa, R. R.; Lippard, S. J.; Kelley, S. O. Targeting mitochondrial DNA with a platinum-based anticancer agent. Chem. Biol. 2013, 20, 1323-1328. 29. Fonseca, S. B.; Pereira, M. P.; Mourtada, R.; Gronda, M.; Horton, K. L.; Hurren, R.; Minden, M. D.; Schimmer, A. D.; Kelley, S. O. Rerouting chlorambucil to mitochondria combats drug deactivation and resistance in cancer cells. Chem. Biol. 2011, 18, 445-453. 30. Pereira, M. P.; Kelley, S. O. Maximizing the therapeutic window of an antimicrobial drug by imparting mitochondrial sequestration in human cells. J. Am. Chem. Soc. 2011, 133, 3260-3263. 31. Pereira, M. P.; Shi, J.; Kelley, S. O. Peptide Targeting of an Antibiotic Prodrug toward Phagosome-Entrapped Mycobacteria. ACS Infect. Dis. 2015, 1, 586-592. 32. Jean, S. R.; Ahmed, M.; Lei, E. K.; Wisnovsky, S. P.; Kelley, S. O. Peptide-Mediated Delivery of Chemical Probes and Therapeutics to Mitochondria. Acc. Chem. Res. 2016, 49, 1893-1902. 33. Wisnovsky, S.; Jean, S. R.; Kelley, S. O. Mitochondrial DNA repair and replication proteins revealed by targeted chemical probes. Nat. Chem. Biol. 2016, 12, 567-573. 34. Lei, E. K.; Kelley, S. O. Delivery and Release of Small-Molecule Probes in Mitochondria Using Traceless Linkers. J. Am. Chem. Soc. 2017, 139, 9455-9458. 35. Selmin, F.; Magri, G.; Gennari, C. G.; Marchiano, S.; Ferri, N.; Pellegrino, S. Development of poly(lactide-co-glycolide) nanoparticles functionalized with a mitochondria penetrating peptide. J. Pept. Sci. 2017, 23, 182-188. 36. Hidaka, T.; Pandian, G. N.; Taniguchi, J.; Nobeyama, T.; Hashiya, K.; Bando, T.; Sugiyama, H. Creation of a Synthetic Ligand for Mitochondrial DNA Sequence Recognition and Promoter-Specific Transcription Suppression. J. Am. Chem. Soc. 2017, 139, 8444-8447. 37. Yousif, L. F.; Stewart, K. M.; Horton, K. L.; Kelley, S. O. Mitochondria-penetrating peptides: sequence effects and model cargo transport. ChemBioChem. 2009, 10, 2081-2088. 38. Wu, C.-H.; Chen, Y.-P.; Mou, C.-Y.; Cheng, R. P. Altering the Tat-derived peptide bioactivity landscape by changing the arginine side chain length. Amino Acids 2013, 44, 473-480. 39. Wu, C.-H.; Weng, M.-H.; Chang, H.-C.; Li, J.-H.; Cheng, R. P. Effect of each guanidinium group on the RNA recognition and cellular uptake of Tat-derived peptides. Bioorg Med Chem 2014, 22, 3016-3020. 40. Fields, G. B.; Noble, R. L. Solid phase peptide synthesis utilizing 9-fluorenylmethoxycarbonyl amino acids. Int. J. Pept. Protein Res. 1990, 35, 161-214. 41. Cheng, R. P.; Weng, Y.-J.; Wang, W.-R.; Koyack, M. J.; Suzuki, Y.; Wu, C.-H.; Yang, P.-A.; Hsu, H.-C.; Kuo, H.-T.; Girinath, P.; Fang, C.-J. Helix formation and capping energetics of arginine analogs with varying side chain length. Amino Acids 2012, 43, 195-206. 42. Thakkar, A.; Trinh, T. B.; Pei, D. Global analysis of peptide cyclization efficiency. ACS Comb. Sci. 2013, 15, 120-129. 43. Feichtinger, K.; Sings, H. L.; Baker, T. J.; Matthews, K.; Goodman, M. Triurethane-protected guanidines and triflyldiurethane-protected guanidines: New reagents for guanidinylation reactions. J. Org. Chem. 1998, 63, 8432-8439. 44. Feichtinger, K.; Zapf, C.; Sings, H. L.; Goodman, M. Diprotected triflylguanidines: A new class of guanidinylation reagents. J. Org. Chem. 1998, 63, 3804-3805. 45. Suzuki, T.; Fujikura, K.; Higashiyama, T.; Takata, K. DNA staining for fluorescence and laser confocal microscopy. J. Histochem. Cytochem. 1997, 45, 49-53. 46. Fischer, R.; Mader, O.; Jung, G.; Brock, R. Extending the applicability of carboxyfluorescein in solid-phase synthesis. Bioconjug. Chem. 2003, 14, 653-660. 47. Haugland, R. P. Handbook of Fluorescent Probes and Research Chemicals. 6 ed.; Eugene, OR, USA: 1996. 48. Crouch, S. R.; Ingle, J. D. Spectrochemical Analysis. Prentice Hall, New Jersey: 1988. | |
dc.identifier.uri | http://tdr.lib.ntu.edu.tw/jspui/handle/123456789/77533 | - |
dc.description.abstract | 膠原蛋白是人體中最常見的一種蛋白質,由三條右旋的polyproline II螺旋所組成。Xaa-Yaa-Gly是一個在膠原蛋白中常出現的重複序列。脯胺酸(proline)、羥脯胺酸(hydroxyproline)及甘胺酸(glycine)是膠原蛋白中很常出現的胺基酸。除此之外,膠原蛋白也含有高於預期的帶電荷胺基酸,因此在此研究中將不同側鏈長短的帶電荷胺基酸引入異元三聚體膠原蛋白中來研究帶電荷胺基酸側鏈長短對於膠原蛋白穩定性的影響。引入的帶電荷胺基酸分別是天門冬胺酸(Asp)、谷氨酸(Glu)、Aad(側鏈較Glu多一個亞甲基)、Dap(側鏈較Lys少三個亞甲基)、Dab(側鏈較Lys少兩個亞甲基)、Orn(側鏈較Lys少一個亞甲基)及賴氨酸(Lys)。利用圓二色光譜儀來測量膠原蛋白在改變溫度下二級結構的變化以求得其變性的熱力學參數。在更改X位置為負電荷胺基酸的結果中,膠原蛋白穩定度的趨勢為Glu>Aad>Asp;在更改Y位置為負電荷胺基酸的結果中,膠原蛋白穩定度的趨勢為Aad>Glu>Asp。對於在Y位置更改為賴氨酸類似物膠原蛋白的穩定度趨勢為Dab>Dap>Lys>Orn。此結果對於未來設計引入離子對的膠原蛋白有幫助。
粒線體是細胞中不可或缺的胞器,有許多功能包括產生能量、細胞分化、細胞凋亡及細胞的訊息傳遞。當粒線體功能失調時,便會產生許多疾病。一般的藥物無法穿透到粒線體主要是因為粒線體難以通透的內膜。先前對於目標粒線體藥物的研究指出疏水性及正電荷是兩項影響粒線體穿膜的重要因素。在此研究中,將不同疏水性的非自然界胺基酸及不同側鏈長短的精氨酸類似物組合,期望合成出可表現粒線體穿膜的胜肽。將粒線體穿透胜肽接上螢光基團可研究其在細胞中的位置。利用螢光顯微鏡及流式細胞儀來檢測此胜肽在細胞中的位置及含量。研究結果顯示在粒線體穿透胜肽上接了螢光基團fluorescein會使其無法穿透進細胞,而接了螢光基團thiazole orange的粒線體穿透胜肽可進入細胞到達粒線體。未來需合成出更多接有螢光基團thiazole orange的粒線體穿透胜肽組合來研究精氨酸側鏈長短對於粒線體穿透胜肽的影響。 | zh_TW |
dc.description.abstract | Collagen is the most abundant protein in the human body. Collagen forms a right-handed triple helix that consists of three polyproline II-like polypeptide chains. The Xaa-Yaa-glycine repeat are frequently observed in collagen triple helices. Besides, collagen contains more charged residues than expected. Therefore, investigating the effect of charged residues on collagen triple helix should shed light on the stability of collagen. This research focuses on the effect of charged amino acid side chain length on collagen triple helix stability. The collagen triple helices were designed based on an ABC-type heterotrimer collagen. All peptides were synthesized by Fmoc-based solid phase peptide synthesis. After purification, circular dichroism (CD) was used to monitor the thermal denaturation of collagen triple helices and further derive the thermodynamic parameters. The melting temperature, HTm and Gunfold were derived from the thermal denaturation data. The experimental results showed the stability of ABC heterotrimeric collagen triple helices upon incorporating the negatively charged residue at the Xaa position followed the trend Glu>Aad>Asp. The stability of ABC heterotrimeric collagen triple helices upon incorporating the negatively charged residue at the Yaa position followed the trend Aad>Glu>Asp. The stability of ABC heterotrimeric collagen triple helices upon incorporating the positively charged residue at the Yaa position followed the trend Dab>Dap>Lys>Orn. Negatively charged residues with longer side chains provided more collagen triple helix stability, perhaps due to formation of the intrastrand hydrogen bond between the side chain and the earlier glycine carbonyl. For collagen triple helices with a lysine analog incorporated, no correlation was observed between the side chain length and the collagen triple helix stability. Incorporating a charged residue at the Yaa position to replace hydroxyproline resulted in more significant changes in the collagen triple helix stability compared to the Xaa position. These results will be useful for developing collagen triple helices containing aspartic acid and lysine analogs.
Mitochondrion is an important organelle in the cell. Mitochondria perform many functions including energy generation, cell proliferation, cell death programming, and signaling. Mitochondria dysfunction leads to many diseases such as mitochondrial disorder, diabetes, cardiomyopathy and endocrinopathy. Therefore, drug delivery targeting mitochondria is important to the remedy of mitochondria-related diseases. The major difficulty in mitochondrial delivery is the impervious mitochondrial inner membrane. Mitochondria penetrating peptides are drug delivery vehicles for targeting mitochondria. Lipophilicity and positive charge are the major factors affecting mitochondria localization. Besides, peptides with clustered positive charges result in increasing transportation across the plasma membrane, whereas peptides with separated positive charges lead to mitochondrial localization. Altering the side chain length also influences the cellular uptake of the peptide. The mitochondria penetrating peptides were designed upon altering the hydrophobic residues and the side chain length of arginine in mitochondria penetrating peptides. Fluorescence group was attached to the mitochondria penetrating peptides to be visualized by fluorescence microscopy. After purification, the localization and uptake of mitochondria penetrating peptides were analyzed by fluorescence microscopy and flow cytometry. Peptides with fluorescein led to low cellular uptake of the mitochondria penetrating peptides into Hela cells. Conversely, peptides with thiazole orange exhibited higher cellular uptake and mitochondrial localization. Conjugation with fluorescein results in the total charge of one positive charge, which hardly crossed the negatively charged plasma membrane. Therefore, thiazole orange conjugated mitochondria penetrating peptides is required to investigate the effect of arginine side chain length on mitochondria penetrating peptides. These results will lead to further designs of mitochondria penetrating peptides. | en |
dc.description.provenance | Made available in DSpace on 2021-07-10T22:07:22Z (GMT). No. of bitstreams: 1 ntu-107-R05223205-1.pdf: 6555795 bytes, checksum: a254a1451854fa609336f008541571e4 (MD5) Previous issue date: 2018 | en |
dc.description.tableofcontents | 誌謝 i
中文摘要 ii Abstract iv Abbreviations vii List of Figures xi List of Tables xviii List of Schemes xix Chapter 1 Introduction 1-1. Proteins 2 1-2. The Hierarchy of Protein Structure 4 1-3. The Driving Forces of Protein Folding 9 1-4. Charged Amino Acid Side Chain Length 11 1-5. Collagen Triple Helix 12 1-6. Mitochondria Penetrating Peptide 13 1-7. Thesis Overview 13 1-8. References 15 Chapter 2 Effect of Charged Amino Acid Side Chain Length on ABC Heterotrimeric Collagen Triple Helix Stability 2-1. Introduction 20 Structure of Collagen 20 Stability of Collagen Triple Helix 21 The Hysteresis of Collagen Folding 23 Charged Residues in Collagen Triple Helix 23 Design of Heterotrimeric Collagen Mimetic Peptides 26 2-2. Results and Discussion 28 Peptide Design and Synthesis 28 Initial Assessment of Different Combinations 31 Fully Equilibrated Thermal Denaturation 42 2-3. Conclusion 55 2-4. Future aspect 56 2-5. Acknowledgements 57 2-6. Experimental Section 57 General Materials and Methods 57 Peptide Synthesis 58 UV-vis spectroscopy (UV) 67 Circular Dichroism Spectroscopy (CD) 68 2-7. References 73 Chapter 3 Effect of Arginine Side Chain Length on Mitochondria Penetrating Peptides 3-1. Introduction 78 Mitochondrial Delivery 78 Mitochondria Penetrating Peptides 80 Effect of Lipophilictiy and Positive Charge on Mitochondrial Localization 81 3-2. Results and Discussion 84 Peptide Design 84 Peptide Synthesis and Purification 87 Localization of Peptides 89 Cellular Uptake 91 3-3. Conclusion 98 3-4. Future Aspect 98 3-5. Acknowledgements 99 3-6. Experimental Section 100 General Materials and Methods 100 N,N’-Bis(tert-butoxycarbonyl)-guanidine 101 N,N’-Di-boc-N’’-trifluoromethanesulfonyl-guanidine 102 Peptide Synthesis 103 UV-vis Spectroscopy 121 Cell Culture 122 Mitochondrial Localization 123 Cellular Uptake Assay 123 3-7. References 126 3-8. Appendix 130 MitoChondrial Localization 130 | |
dc.language.iso | en | |
dc.title | 帶電荷胺基酸側鏈長短對於ABC異元三聚體膠原蛋白穩定度的影響 | zh_TW |
dc.title | Effect of Charged Amino Acid Side Chain Length on ABC Heterotrimeric Collagen Triple Helix Stability | en |
dc.type | Thesis | |
dc.date.schoolyear | 106-2 | |
dc.description.degree | 碩士 | |
dc.contributor.oralexamcommittee | 陳佩燁,黃人則,何佳安 | |
dc.subject.keyword | 異元三聚體膠原蛋白,非自然界帶電荷胺基酸,變溫變性實驗,粒線體穿透胜?,細胞攝取量, | zh_TW |
dc.subject.keyword | heterotrimeric collagen triple helix,non-natural charged amino acid, thermal denaturation,mitochondria penetrating peptides,mitochondrial localization,cellular uptake, | en |
dc.relation.page | 148 | |
dc.identifier.doi | 10.6342/NTU201802802 | |
dc.rights.note | 未授權 | |
dc.date.accepted | 2018-08-13 | |
dc.contributor.author-college | 理學院 | zh_TW |
dc.contributor.author-dept | 化學研究所 | zh_TW |
顯示於系所單位: | 化學系 |
文件中的檔案:
檔案 | 大小 | 格式 | |
---|---|---|---|
ntu-107-R05223205-1.pdf 目前未授權公開取用 | 6.4 MB | Adobe PDF |
系統中的文件,除了特別指名其著作權條款之外,均受到著作權保護,並且保留所有的權利。