A humanized antibody inhibitor for cathepsin L

Xiaojing Shi; Yong Zhang

doi:10.1002/pro.3913

A humanized antibody inhibitor for cathepsin L

Protein Sci. 2020 Sep;29(9):1924-1930. doi: 10.1002/pro.3913. Epub 2020 Aug 7.

Authors

Xiaojing Shi¹, Yong Zhang^{1

2

3

4}

Affiliations

¹ Department of Pharmacology and Pharmaceutical Sciences, School of Pharmacy, University of Southern California, Los Angeles, California, USA.
² Department of Chemistry, Dornsife College of Letters, Arts and Sciences, University of Southern California, Los Angeles, California, USA.
³ Norris Comprehensive Cancer Center, University of Southern California, Los Angeles, California, USA.
⁴ Research Center for Liver Diseases, University of Southern California, Los Angeles, California, USA.

Abstract

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.

Keywords: antibody; cathepsin L; protease inhibitor; protein engineering.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Antibodies, Monoclonal, Humanized / chemistry*
Antibodies, Monoclonal, Humanized / genetics
Cathepsin L / antagonists & inhibitors*
Cathepsin L / chemistry*
Cathepsin L / genetics
Cysteine Proteinase Inhibitors / chemistry*
Humans

Substances

Antibodies, Monoclonal, Humanized
Cysteine Proteinase Inhibitors
CTSL protein, human
Cathepsin L