Evaluation of the self-cleavage conditions of the Intein bound to the ACE1 catalytic sites.

• Grant number: 24/03334-1
• Support Opportunities: Scholarships in Brazil - Scientific Initiation
• Start date: June 01, 2024
• End date: December 31, 2024
• Field of knowledge: Health Sciences - Medicine
• Principal Investigator: Regina Affonso
• Grantee: Victoria Aragão Marques da Silva
• Host Institution: Instituto de Pesquisas Energéticas e Nucleares (IPEN). Secretaria de Desenvolvimento Econômico (São Paulo - Estado). São Paulo , SP, Brazil

Abstract

Cardiovascular and pulmonary diseases are theprincipal public health problems currently affecting the world (WHO/2020), which have in common the renin-angiotensin system. This system acts in the pressure regulation and on the salt balance in the human body. In this system, the angiotensin-converting enzyme 1 (ACE1) acts in arterial pressure control, brain protection by cleavage of beta-amyloid bodies, cellular proliferation, and hematopoietic stem cells, among others. Peptides for diagnosis and therapy are a reality in broad expansion, and the catalytic regions of ACE1 can be worthy tools to solution these dysfunctions. The objective of this work will be to obtain the catalytic sites of the N and C regions of the ACE1 pure with the correct conformation. These peptides were already produced and purified, and they are in the cleavage phase Intein sequence, which releases the ELP sequence (elastin polypeptide) to the obtention of these pure sites. The methodology that will initially be employed will be analysis of the action of four different buffers with different acids pH. These two pure peptides will enable greater assertiveness in obtaining and characterization new anti-hypertensive drugs, both evaluating the hydrolysis capacity of substrates such as amyloid beta.