Strategies for the Synthesis of Novel Glycoconjugates

Abstract

A chemical reaction wherein two individual molecules are coupled together covalently in the presence or absence of reagents is known as a conjugation reaction and if the reacting partners are biomolecules then it is known as bioconjugation. If the two reacting partners are saccharide and nucleobase, then, the conjugate is called as nucleoside and if a conjugate is prepared from two saccharides then, it can be termed as disaccharide. Conjugation of molecules is important for studying various cellular events such as interactions between them, imaging of cells, for the measurement of distances between epitopes, for modification of materials, etc. Amidation, Native Chemical Ligation, Staudinger ligation, azide-alkyne involved [3+2] cycloaddition (‘click’ reaction), olefin metathesis, imine formation, tetrazine-based ligation, Michael addition are some of the bioconjugation methods; among these, Staudinger ligation, tetrazine-based ligation and click reaction are the most popular and bioorthogonal conjugations. In my thesis entitled, Strategies for the Synthesis of Novel Glycoconjugates, we showed that various pseudo-saccharide conjugates such as pyrimidine nucleosides, thiosaccharides and thiotrehaloses can be synthesized by utilizing concepts from gold-catalyzed glycosylation repertoire on designer mono-saccharide building blocks. Most of the above methods and the one that I delineated above are useful to study binary complexes as only two partners participate in the conjugation. In contrast, methods for multi- and poly- valent display of single molecule exploiting dendrimers, nanoparticles, calixarenes etc as templates are known. However, stepwise conjugation of molecules to get ternary complexes in a modular fashion is still challenging. In my next attempt, we have successfully utilized dichlorotetrazine as a template for the synthesis of ternary conjugates in a modular fashion exploiting SNAr and Inverse Electron Demand Diels-Alder reactions. We have successfully synthesized a ternary conjugate that has fucp-, manp- and galp- residues.