Characterization of ditryptophan and tryptophan-tyrosine cross-links: A step to a better understanding of protein aggregation

• Grant number: 24/18247-7
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: November 01, 2024
• End date: August 31, 2026
• Field of knowledge: Physical Sciences and Mathematics - Chemistry - Organic Chemistry
• Principal Investigator: Ohara Augusto
• Grantee: Amanda Capistrano Pinheiro
• Host Institution: Instituto de Química (IQ). Universidade de São Paulo (USP). São Paulo , SP, Brazil
• Associated research grant: 13/07937-8 - Redoxome - Redox Processes in Biomedicine, AP.CEPID

Abstract

Protein oxidation is an unavoidable consequence of aerobic metabolism. The oxidation of most proteins residues is non-repairable and may affect protein structure and function. In particular, protein cross-links are toxic to cells because they may accumulate and induce protein aggregation, which is a hallmark of aging-related diseases. However, most of these irreversible protein cross links remain partially characterized, including Trp-Trp and Trp-Tyr cross-links. Here, we will try to synthesize model dimers bound by Trp-Trp and Trp-Tyr cross-links in sufficient amounts to determine their chemical nature and properties. This is an important step not only for the detection of Trp-Trp and Trp-Tyr cross-links in peptides and proteins, but also for a better understanding of the protein aggregation process