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

Abstract

The human tissue kallikreins (KLKs) comprise a family of fifteen serine proteases found in a diversity of biological fluids and tissues. These enzymes are identified as having function in different diseases such as Alzheimer's, cancer, atopic dermatitis, multiple sclerosis, Parkinson's, psoriasis, and others. Thus there is a growing demand for specific inhibitors for each of these kallikreins, and this is the aim of our group at UFABC. Particularly in my PhD research, we are developing a library of recombinant serpins based on the amino acid sequence from Gloeobacter violaceus. The use of phage display technique to optimize libraries construction drew our attention, and we made contact with Prof. William Sheffield, from McMaster University, Canada, who has a wide experience in the development of recombinant serpins libraries through phage display, and has accepted to receive me in his lab for an one year internship, where we intend to generate inhibitors for the human tissue kallikreins 3 and 5, using the approach of the phage display based in the sequence of the human inhibitor alpha-1 antitrypsin. (AU)