Development of inhibitors for human tissue kallikreins 5 and 7 (KLK5 and KLK7)

• Grant number: 11/51297-8
• Support Opportunities: Regular Research Grants
• Start date: February 01, 2012
• End date: September 30, 2013
• Field of knowledge: Biological Sciences - Biochemistry - Enzymology
• Principal Investigator: Luciano Puzer
• Grantee: Luciano Puzer
• Host Institution: Centro de Ciências Naturais e Humanas (CCNH). Universidade Federal do ABC (UFABC). Ministério da Educação (Brasil). Santo André , SP, Brazil

Abstract

Human kallikreins 5 (KLK5) and 7 (KLK7) are members of the human tissue kallikreins, comprising 15 kallikrein like serine peptidases (KLKs). KLK5 is found in many tissues, including breast, central nervous system, prostate, testis and trachea; and KLK7 was reported to be present at esophagus, kidney, liver and salivary gland. Moreover, both enzymes appear to be most abundantly expressed in human skin, where an important role in the skin desquamation process has been reported. In the extracellular space, KLK5 and KLK7 are believed to contribute to desquamation by hydrolyzing proteins composing intercellular adhesion structures called corneodesmosomes. Thus, the development of inhibitor for KLK5 and KLK7 can contribute not only to elucidate its physiological and pathological mechanisms but also as an archetype of new drugs whose hinder such complications caused by KLK5 and KLK7 uncontrolled activity. Thus, in this project, we will strive in the search for inhibitors for KLK5 and KLK7 using synthetic molecules and protein inhibitors. The molecules are peptidomimetic based compounds and bacterial serpins. (AU)

Scientific publications

(References retrieved automatically from Web of Science and SciELO through information on FAPESP grants and their corresponding numbers as mentioned in the publications by the authors)

FREITAS, RENATO F.; TEIXEIRA, THIAGO S. P.; BARROS, THALITA G.; SANTOS, JORGE A. N.; KONDO, MARCIA Y.; JULIANO, MARIA A.; JULIANO, LUIZ; BLABER, MICHAEL; ANTUNES, OCTAVIO A. C.; ABRAHAO, JR., ODONIRIO; et al. Isomannide derivatives as new class of inhibitors for human kallikrein 7. Bioorganic & Medicinal Chemistry Letters, v. 22, n. 19, p. 6072-6075, OCT 1 2012. (11/51297-8)

OLIVEIRA, JOCELIA P. C.; FREITAS, RENATO F.; DE MELO, LEANDRO SILVA; BARROS, THALITA G.; SANTOS, JORGE A. N.; JULIANO, MARIA A.; PINHEIRO, SERGIO; BLABER, MICHAEL; JULIANO, LUIZ; MURI, ESTELA M. F.; et al. Isomannide-Based Peptidomimetics as Inhibitors for Human Tissue Kallikreins 5 and 7. ACS Medicinal Chemistry Letters, v. 5, n. 2, p. 128-132, FEB 2014. (12/50191-4, 11/51297-8)

DE SOUZA, LUCAS R.; MELO, POLLYANA M.; PASCHOALIN, THAYSA; CARMONA, ADRIANA K.; KONDO, MARCIA; HIRATA, IZAURA Y.; BLABER, MICHAEL; TERSARIOL, IVARNE; TAKATSUKA, JOYCE; JULIANO, MARIA A.; et al. Human tissue kallikreins 3 and 5 can act as plasminogen activator releasing active plasmin. Biochemical and Biophysical Research Communications, v. 433, n. 3, p. 333-337, APR 12 2013. (11/51297-8)

Filed patent(s) as a result of this research project