多肽化合物AcSDKP衍生物的设计与合成
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摘要
【目的】以AcSDKP为先导结构,设计并合成具有化学损伤防护活性的多肽化合物。【方法】采用固相多肽合成或液相方法获得目标产物,涉及的结构改造方式主要有C末端的修饰、N末端的修饰、侧链修饰与残基的位点改造等。【结果】17个目的产物结构经LC-MS分析证明,相对分子质量与理论值一致;粗产物经RP-HPLC分离分析,纯度达到95%以上。【结论】通过本设计与合成工作,为开发具有化学损伤保护活性的新药提供实验依据。
【Objective】To design and synthesize the polypeptide compounds with chemical damage protection activity in a lead structure of Ac SDKP. 【Methods】 Target products were prepared by solid phase peptide synthesis or liquid phase method. The structural transformation modes included substitution or modification of N-, C-terminus, or side chains with unnatural building blocks as the surrogates for normal residues.【Results】The structures of 17 target products were confirmed by LC-MS analysis that the relative molecular weight was consistent with the theoretical value, and the purity of the crude product was over 95% by RP-HPLC separation and analysis.【Conclusion】By the design and synthesis, the experimental basis is provided for the development of new drugs with chemical damage protection activity.
【Objective】To design and synthesize the polypeptide compounds with chemical damage protection activity in a lead structure of Ac SDKP. 【Methods】 Target products were prepared by solid phase peptide synthesis or liquid phase method. The structural transformation modes included substitution or modification of N-, C-terminus, or side chains with unnatural building blocks as the surrogates for normal residues.【Results】The structures of 17 target products were confirmed by LC-MS analysis that the relative molecular weight was consistent with the theoretical value, and the purity of the crude product was over 95% by RP-HPLC separation and analysis.【Conclusion】By the design and synthesis, the experimental basis is provided for the development of new drugs with chemical damage protection activity.
引文
[1]高月,马增春.辐射损伤防治药物发展历史与展望[J].辐射防护通讯.2009,29(5):30-35.
[2]Liu JM,Garcia-Alvarez MC,Bignon J,et al.Overexpression of the natural tetrapeptide acetyl-N-ser-asp-lys-pro derived from thymosin beta4 in neoplastic diseases[J].Ann N Y Acad Sci,2010,1194:53-59.
[3]韩香,王德心.多肽调控因子Ac SDKP的生物学活性及构效关系研究进展[J].药学学报,2007,42(8):810-816.
[4]Fosgerau K,Hoffmann T.Peptide therapeutics:current status and future directions[J].Drug Discovery Today,2015,20(1):122-128.
[5]Laszlo Otvos Jr,John D Wade.Current challenges in peptidebased drug discovery[J].Frontiers in Chemistry,2014,2(62):1-4.
[2]Liu JM,Garcia-Alvarez MC,Bignon J,et al.Overexpression of the natural tetrapeptide acetyl-N-ser-asp-lys-pro derived from thymosin beta4 in neoplastic diseases[J].Ann N Y Acad Sci,2010,1194:53-59.
[3]韩香,王德心.多肽调控因子Ac SDKP的生物学活性及构效关系研究进展[J].药学学报,2007,42(8):810-816.
[4]Fosgerau K,Hoffmann T.Peptide therapeutics:current status and future directions[J].Drug Discovery Today,2015,20(1):122-128.
[5]Laszlo Otvos Jr,John D Wade.Current challenges in peptidebased drug discovery[J].Frontiers in Chemistry,2014,2(62):1-4.