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Development of a recombinant serpins library for specificity study of the human tissue kallikreins

Grant number: 13/09202-5
Support type:Scholarships in Brazil - Doctorate
Effective date (Start): August 01, 2013
Effective date (End): June 19, 2017
Field of knowledge:Biological Sciences - Biochemistry - Enzymology
Principal Investigator:Luciano Puzer
Grantee:Lucas Rodrigo de Souza
Home Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil
Associated scholarship(s):15/17149-2 - Development of inhibitors for human tissue kallikreins 3 and 5 (KLK3 and KLK5) through a phage display library based on the human alpha-1 antitrypsin, BE.EP.DR

Abstract

Human tissue kallikreins (KLKs) are a group of serine proteases found in many tissues and cells, therefore they are related to a variety of physiological processes. Kallikreins also catch attention for being differentially expressed in cancer tissues, what suggests that they can be used as cancer biomarkers. Several studies with fluorescent peptides have contributed towards the characterization of some KLKs specificity, and to the development of selective and/or specific substrates for monitoring the proteolytic activity of these enzymes. However, such substrates are less efficient to the search of natural substrates.Serpins are a family of serine protease inhibitors which main structural characteristic is the presence of a loop with approximately 20 amino acids known as reactive center loop (RCL). These inhibitors act through irreversible inhibition, in which the RCL takes role of a canonic substrate, and suffers a proteolytic cleavage. The cleavage leads to a great serpin's conformational change that consequently modifies the enzyme and catalytic site structures, stopping the mechanism of proteolysis.In this project we intend to create a library of recombinant serpins from randomic mutations in the reactive center loop of Gloeobacter violaceus's serpin. The recombinant serpin's library will be used to perform specificity studies of the KLKs. (AU)