Metabolically stabilized structural modification on the helix B surface peptide of erythropoietin: Design, synthesis and improved renoprotective effect

	Metabolically stabilized structural modification on the helix B surface peptide of erythropoietin: Design, synthesis and improved renoprotective effect
	Peng Dian 3; Xu Zhongliang 4; Yang Cheng 5; Rong Ruiming 5; Zhu Tongyu 5; Long Yaqiu 4
刊名	Scientia Sinica Chimica
	2013
卷号	43 期号:8 页码:1033-1040
关键词	cyclic peptide metabolic stability erythropoietin microwave-assisted peptide synthesis kidney ischemia reperfusion injury renal transplanting tissue protective effect
ISSN号	1674-7224
其他题名	促红细胞生成素B螺旋表面肽的代谢稳定性结构修饰:设计、合成及其提高的肾保护作用
文献子类	Article
英文摘要	Kidney ischemia reperfusion (IR) injury is a major cause of delayed graft function and can increase the risk of allograft rejection, affecting both short- and long-term graft survivals. It has been recently shown that helix B surface peptide (HBSP), an 11-amino acid long sequence derived from the aqueous surface of the helix B domain of erythropoietin, has powerful tissue protective function in various organs subjected to IR injury. However, the 2 minplasma half-life of HBSP restricts its application in vivo. In this study, conformationally constraining, all D-amino acid replacement and N-capping strategies were employed to modify the structure and thus improved the metabolic stability of the linear peptide HBSP. The redox-stable thioether and relatively rigid sulfoxide were chosen as the linkage to tether the 11-amino acid binding motif. For the synthesis of these peptide derivatives, microwave peptide synthesizer and manual solid peptide synthesis were combined to improve the efficiency. Especially, microwave assisted macrocyclization greatly facilitated the production of the thioether-cyclized peptide. The configuration of the chiral sulfoxide linkage was identified by CD spectra. Significantly, the renal functional assay in a murine kidney IR model indicated that these metabolically stabilized derivatives displayed improved renal protective effect compared to the linear parent peptide. Furthermore, the thioether-cyclized peptide was superior to the sulfoxide-cyclized peptide with respect to reducing the serum creatinine level. Therefore, the TE-CHBP with one dose in one week maintained equal renoprotective effect to the HBSP with 3 doses in one week in murine kidney ischemia reperfusion (IR) model.
资助项目	国家自然科学基金[00000000] ; 上海市科学技术委员会基金[00000000]
WOS研究方向	Pharmacology & Pharmacy (provided by Clarivate Analytics)
语种	中文
CSCD记录号	CSCD:4916609
内容类型	期刊论文
源URL	[http://119.78.100.183/handle/2S10ELR8/267760]
专题	中国科学院上海药物研究所
作者单位	1.Shanghai Institute of Materia Medica, Chinease Academy of Sciences, Shanghai 201203, China.; 2.Zhongshan Hospital, Fudan University, Shanghai 200032, China. 3.Department of Pharmacology, Changsha Medical College, CAS Key Laboratory of Receptor Research, Changsha, Hunan 410219, China.; 4.CAS Key Laboratory of Receptor Research; 5.Shanghai Key Laboratory of Organ Transplantation;
推荐引用方式 GB/T 7714	Peng Dian,Xu Zhongliang,Yang Cheng,et al. Metabolically stabilized structural modification on the helix B surface peptide of erythropoietin: Design, synthesis and improved renoprotective effect[J]. Scientia Sinica Chimica,2013,43(8):1033-1040.
APA	Peng Dian,Xu Zhongliang,Yang Cheng,Rong Ruiming,Zhu Tongyu,&Long Yaqiu.(2013).Metabolically stabilized structural modification on the helix B surface peptide of erythropoietin: Design, synthesis and improved renoprotective effect.Scientia Sinica Chimica,43(8),1033-1040.
MLA	Peng Dian,et al."Metabolically stabilized structural modification on the helix B surface peptide of erythropoietin: Design, synthesis and improved renoprotective effect".Scientia Sinica Chimica 43.8(2013):1033-1040.