Protein cross-links produced by radical mechanisms: characterization and roles in protein aggregation

• Grant number: 20/15548-5
• Support Opportunities: Scholarships in Brazil - Post-Doctoral
• Start date: June 01, 2021
• End date: December 31, 2021
• Field of knowledge: Biological Sciences - Biochemistry
• Principal Investigator: Ohara Augusto
• Grantee: Andrezza da Silva Ramos
• 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

Our lab constructed a MS database of the soluble fraction of human crystalline from patients submitted to cataract surgery and was able to publish part of these results recently. This publication constituted the first characterization of Trp-Trp and Trp-Tyr cross-links in biological samples. To progress in the understanding of the role of these cross-links in the pathogenic mechanism of human diseases, we need the input of an investigator able to fully characterize by NMR the cross-links formed by radical mechanisms such as Trp-Trp and Trp-Tyr. Indeed, the radicals that produce such cross-links are stabilized by resonance and, therefore are able to produce different isomeric cross-links. We also need to develop a protocol to obtain proteomic MS data to analyze these cross-links in the aggregates of human crystalline and in other samples from animal models and/or patients of other diseases associated with protein aggregation. The project falls within the CEPID Redoxoma goals, particularly goal 1 (Biomolecule oxidation & function). (AU)