Scientific seminar «Organometallic Palladium Reagents for Cysteine Bioconjugation»

3 December at 15:00 MSK

Bioconjugation reactions that can operate on proteins are recognized as important tools for probing structure-function relationships, developing new therapeutics, and providing total chemical synthesis routes.  Outside of enzymatic techniques, two methods for site-specific chemical modification of proteins are commonly employed that rely on: (1) installation of a non-canonical amino acid possessing a side chain with unique reactivity or (2) especially reactive natural amino acids that are present in low abundance. In the former strategy, click chemistry provides a means for the site-specific conjugation of both small and large molecules onto proteins.

Click reactions can be used to produce homogeneous products by exploiting orthogonal reactivity, but require the installation of the non-natural functional groups into each piece to enable the conjugation. The latter approach obviates the need to install two orthogonal, non-canonical reactive partners on separate components by chemoselectively targeting particularly reactive native amino acid residues. In this regard, cysteine side chains, owing to their low natural abundance and the unique reactivity of the thiol functional group, provide an attractive opportunity for site-specific modification of proteins.  A practical strategy for chemical bioconjugation of native proteins using Pd reagents, allowing for both coupling partners to be comprised of only canonical amino acids while maintaining site-specificity is reported.

Participants: students, postgraduates and scientific-pedagogical workers of the faculty of Sciences of RUDN and other Universities.

Online