Synthesis of Multiply Substituted Cyclosporine Analogs
碩士 === 國防醫學院 === 藥學研究所 === 85 === Cyclosporin A (CsA, Figure 1) is a naturally occurring cyclo-undecapeptide which is currently an important important immunosuppressive drug for preventing graft rejection during tissue transplantation. In addition, CsA also displays blockade of P-glycoprotein-mei...
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ndltd-TW-085NDMC35510062015-10-13T18:05:27Z http://ndltd.ncl.edu.tw/handle/66236975452094456363 Synthesis of Multiply Substituted Cyclosporine Analogs 多重取代的環孢靈素類似物的合成 楊福助 碩士 國防醫學院 藥學研究所 85 Cyclosporin A (CsA, Figure 1) is a naturally occurring cyclo-undecapeptide which is currently an important important immunosuppressive drug for preventing graft rejection during tissue transplantation. In addition, CsA also displays blockade of P-glycoprotein-meidated multidrug resistance in tur or cells and inhibits replication of human immunodeficiency virus in vitro. Recently, Sandoz reported that SDZ NIM 811 [(MeIle4)CsA], a 4-position-modified CsA analogure strogue strongly inhibited replication of HIV-1 in vitro with different mechanism of actions, showed a non-immunosuppressive activity and lower toxicity. Furthermore, PSC 833 [(3-Oxo-MeBmt1, Val2)CsA]was demonstrated to block multidrug resistance in tumor cells. In our laboratory, we modified CsA at the 1, 2, 4 or 6-positions with stretegies regards with conformational constraint and multiple substitutions. A series of coupling reagents such as BOP, PyBrOP, PyBOP and BOP-Cl were compared for the couplings peptide fragments and amino-acids. We found that PyBOP was also a suitable coupling reagent for steric-hindered amino acid derivatives in some cases. New CsA derivatives: [(MePhe1)CsA], [(MePhe1, MeIle4)CsA], [(MePhe1, MeIle6)CsA], [(MePhe1, MeIle4, MeIle6)CsA], [(MePhe1, MeVal6)CsA], [(MePhe1, Leu4, MeIle6)CsA] were obtained and their structures were determined with HR-FABMS and NMR spectra. The relative pharmacological tests of these products were evaluated for future study. 胡明寬 1997 學位論文 ; thesis 182 zh-TW |
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碩士 === 國防醫學院 === 藥學研究所 === 85 ===
Cyclosporin A (CsA, Figure 1) is a naturally occurring cyclo-undecapeptide which is currently an important important immunosuppressive drug for preventing graft rejection during tissue transplantation. In addition, CsA also displays blockade of P-glycoprotein-meidated multidrug resistance in tur or cells and inhibits replication of human immunodeficiency virus in vitro.
Recently, Sandoz reported that SDZ NIM 811 [(MeIle4)CsA], a 4-position-modified CsA analogure strogue strongly inhibited replication of HIV-1 in vitro with different mechanism of actions, showed a non-immunosuppressive activity and lower toxicity. Furthermore, PSC 833 [(3-Oxo-MeBmt1, Val2)CsA]was demonstrated to block multidrug resistance in tumor cells.
In our laboratory, we modified CsA at the 1, 2, 4 or 6-positions with stretegies regards with conformational constraint and multiple substitutions. A series of coupling reagents such as BOP, PyBrOP, PyBOP and BOP-Cl were compared for the couplings peptide fragments and amino-acids. We found that PyBOP was also a suitable coupling reagent for steric-hindered amino acid derivatives in some cases. New CsA derivatives: [(MePhe1)CsA], [(MePhe1, MeIle4)CsA], [(MePhe1, MeIle6)CsA], [(MePhe1, MeIle4, MeIle6)CsA], [(MePhe1, MeVal6)CsA], [(MePhe1, Leu4, MeIle6)CsA] were obtained and their structures were determined with HR-FABMS and NMR spectra. The relative pharmacological tests of these products were evaluated for future study.
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author2 |
胡明寬 |
author_facet |
胡明寬 楊福助 |
author |
楊福助 |
spellingShingle |
楊福助 Synthesis of Multiply Substituted Cyclosporine Analogs |
author_sort |
楊福助 |
title |
Synthesis of Multiply Substituted Cyclosporine Analogs |
title_short |
Synthesis of Multiply Substituted Cyclosporine Analogs |
title_full |
Synthesis of Multiply Substituted Cyclosporine Analogs |
title_fullStr |
Synthesis of Multiply Substituted Cyclosporine Analogs |
title_full_unstemmed |
Synthesis of Multiply Substituted Cyclosporine Analogs |
title_sort |
synthesis of multiply substituted cyclosporine analogs |
publishDate |
1997 |
url |
http://ndltd.ncl.edu.tw/handle/66236975452094456363 |
work_keys_str_mv |
AT yángfúzhù synthesisofmultiplysubstitutedcyclosporineanalogs AT yángfúzhù duōzhòngqǔdàidehuánbāolíngsùlèishìwùdehéchéng |
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1718027805302718464 |