A humanized antibody inhibitor for cathepsin L

被引:20
|
作者
Shi, Xiaojing [1 ]
Zhang, Yong [1 ,2 ,3 ,4 ]
机构
[1] Univ Southern Calif, Dept Pharmacol & Pharmaceut Sci, Sch Pharm, Los Angeles, CA 90007 USA
[2] Univ Southern Calif, Dept Chem, Dornsife Coll Letters Arts & Sci, Los Angeles, CA 90007 USA
[3] Univ Southern Calif, Norris Comprehens Canc Ctr, Los Angeles, CA 90007 USA
[4] Univ Southern Calif, Res Ctr Liver Dis, Los Angeles, CA 90007 USA
关键词
antibody; cathepsin L; protease inhibitor; protein engineering; TRANSITION-STATE ANALOGS; PLASMODIUM-FALCIPARUM; RATIONAL DESIGN; CATALYTIC SITE; SELECTIVITY; PROPEPTIDE; PROTEASES; POTENCY;
D O I
10.1002/pro.3913
中图分类号
Q5 [生物化学]; Q7 [分子生物学];
学科分类号
071010 ; 081704 ;
摘要
Cathepsin L (CTSL) is a cysteine protease involved in a variety of physiological and pathological processes. Potent inhibitors against CTSL have long been sought for drug development. Due to insufficient specificity and suboptimal pharmacological properties for current CTSL inhibitors, novel agents are still required for selectively blocking CTSL activity. Here we generated a humanized antibody inhibitor of CTSL by genetically fusing the inhibitory propeptide of procathepsin L to the N-terminus of the light chain of a humanized antibody. The resulting antibody fusion could be stably expressed and displays highly potent inhibition activity and specificity toward CTSL. This work demonstrates a new approach for the rapid generation of antibody inhibitors of CTSL. It can possibly be extended to create inhibitory antibodies targeting other cathepsin proteases, providing novel research and therapeutic tools.
引用
收藏
页码:1924 / 1930
页数:7
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