机构:[1]Key Laboratory of Animal Models and Human Disease Mechanisms of The Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming, Yunnan 650223, China云南省第一人民医院[2]Department of Urology, The First Affiliated Hospital of Kunming Medical College, Kunming, Yunnan 650032, China外科科室泌尿外科昆明医科大学附属第一医院[3]Graduate School of The Chinese Academy of Science, Beijing 100049, China[4]Biochemistry Section of Kunming Medical College, Kunming, Yunnan 650031, China
King cobra cathelicidin (OH-CATH) is composed of 34 amino acid residues having strong antibacterial and very weak hemolytic activities as reported by us recently. OH-CATH can be served as a valuable template to develop novel therapeutic drugs. In this study, OH-CATH and six of its analogs were synthesized to explore their structure-function relationships based on their bactericidal and hemolytic activities. Experimental results of OH-CATH(3-34) and OH-CATH(5-34) indicated that the N-terminal 4 amino acid residues of OH-CATH played an important role on its hemolytic activity but had weak effects on its bactericidal activity. Among OH-CATH and its analogs, OH-CATH(5-34) had the lowest hemolytic activity while maintained strong antimicrobial activity. To evaluate its potential usage, the biological activities of OH-CATH(5-34) were compared with those of pexiganan. The bactericidal activity of OH-CATH(5-34) against 5 different species (11 laboratory strains) was 2-4 times stronger than that of pexiganan (4-16 mu g/ml vs 8-32 mu g/ml). Hemolytic activity of OH-CATH(5-34) against human erythrocytes was 0.69% while that of pexiganan was 16.5% at the dosage of 200 mu g/ml. OH-CATH(5-34) showed very weak cytotoxic activities against primary rabbit ventricular endothelial cells and four human cancer cell lines whereas pexiganan showed strong cytotoxic activity against these five cell lines (IC50=20-90 mu g/ml). The intravenous LD50 value of OH-CATH(5-34) on mice was 7-fold higher than that of pexiganan (175 mg/kg vs 25 mg/kg). Taken together, our results suggested that OH-CATH(5-34) should be considered as an excellent candidate for developing therapeutic drugs. (C) 2010 Elsevier Inc. All rights reserved.
基金:
National Basic Research Program of China (973 Program)National Basic Research Program of China [2010CB529800]; National Science & Technology Major Project [2009ZX09103-147]; Chinese National Natural Science FoundationNational Natural Science Foundation of China [30630014, 30960384]; Chinese Academy of SciencesChinese Academy of Sciences [KSCX2-YW-R-088, KSCX2-YW-R-212]; Yunnan Science and Technology Commission [2005PY01-23]
第一作者机构:[1]Key Laboratory of Animal Models and Human Disease Mechanisms of The Chinese Academy of Sciences & Yunnan Province, Kunming Institute of Zoology, The Chinese Academy of Sciences, Kunming, Yunnan 650223, China[3]Graduate School of The Chinese Academy of Science, Beijing 100049, China
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推荐引用方式(GB/T 7714):
Zhang Yong,Zhao Hui,Yu Guo-Yu,et al.Structure-function relationship of king cobra cathelicidin[J].PEPTIDES.2010,31(8):1488-1493.doi:10.1016/j.peptides.2010.05.005.
APA:
Zhang, Yong,Zhao, Hui,Yu, Guo-Yu,Liu, Xiao-Dong,Shen, Ji-Hong...&Zhang, Yun.(2010).Structure-function relationship of king cobra cathelicidin.PEPTIDES,31,(8)
MLA:
Zhang, Yong,et al."Structure-function relationship of king cobra cathelicidin".PEPTIDES 31..8(2010):1488-1493