Structure-function of glycosaminoglycans: redundancy, plasticity and probabilities of the constituent disaccharide units

• Grant number: 22/11423-9
• Support Opportunities: Scholarships in Brazil - Program to Stimulate Scientific Vocations
• Start date: January 09, 2023
• End date: March 10, 2023
• Field of knowledge: Biological Sciences - Biochemistry - Molecular Biology
• Principal Investigator: Helena Bonciani Nader
• Grantee: Mariana Amorim Thaumaturgo da Silva
• Host Institution: Instituto Nacional de Farmacologia (INFAR). Universidade Federal de São Paulo (UNIFESP). Campus São Paulo. São Paulo , SP, Brazil

Abstract

The glycoconjugates, including glycosaminoglycans (GAGs), belong to the most abundant class of structurally diverse and heterogeneous molecules present in the extracellular matrix and on the cell surface. Unlike nucleic acids and proteins, the information necessary for their biosynthesis does not have a known code. The diverse and heterogeneous structures are the result of the action of glycosyltransferases, epimerases and sulfotransferases that alter the substitution pattern and stereochemistry of sugar residues at specific sites along each polysaccharide chain. As a result, at the end of biosynthesis, there will be large number of structurally and functionally distinct functional chemical entities. The GAGs structure- function relationship is an example of a complex biological system where there is redundancy, and its plasticity is brought to life via the number of possibilities for only one of its constituent disaccharide units. Several questions remain to be answered regarding the structure of GAGs and therefore their functions and one of the key aspects to this approach is the understanding of their biosynthesis. This project aims to study the role of GAGs in cell biology using different models and approaches whose results are complementary and essential to achieve the objectives: 1) Functional complex among cell surface proteoglycans (PGs), integrins, cell receptors and extracellular matrix components; 2) PGs in cellular cargo trafficking; 3) and GAG fragments: structural features and disaccharide sequence and conformational studies; 4) GAG in cellular transformation. (AU)