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New frontiers in structural proteomics: advances in in vivo experiments using the genetically encoded unnatural amino acids

Grant number: 15/01601-3
Support type:Scholarships abroad - Research Internship - Doctorate
Effective date (Start): May 11, 2015
Effective date (End): December 10, 2015
Field of knowledge:Physical Sciences and Mathematics - Chemistry - Organic Chemistry
Principal researcher:Fabio Cesar Gozzo
Grantee:Mariana Fioramonte
Supervisor abroad: Lei Wang
Home Institution: Instituto de Química (IQ). Universidade Estadual de Campinas (UNICAMP). Campinas , SP, Brazil
Research place: University of California, San Francisco (UCSF), United States  
Associated to the scholarship:12/10862-7 - Structural Proteomics by Chemical Cross-linking Coupled to Mass Spectrometry: Development, Fundamental Studies and Applications., BP.DR

Abstract

The chemical cross-linking coupled to mass spectrometry (MS) is one of the main techniques for protein and protein complex structural characterization when none of the high resolution techniques can be applied. Our laboratory has specialized and worked successfully on developing and applying this technique in protein and protein complexes in vitro. The next big step for this technique is to perform in vivo experiments, what represents the last degree of sophistication in this area. In this context, the genetic code incorporation of unnatural amino acids (UAA) is a tool with huge potential to enable in vivo cross-linking studies. Prof. Lei Wang is one of the main researchers on this area and he has been working on new UAA's that has reactivity enhanced by proximity to nucleophilic amino acids side chains. In this way, it is possible to use these UAA's to find protein partners in vivo and use MS to idenitify the proteins and the interaction regions. Therefore, the junction of the two techniques presents a great potential to develop new methodologies in the protein interaction area, acting on the frontier of both techniques, besides being extremely beneficial for both laboratories and to bring to Brazil a new and inexistent technique with elevated impact. (AU)