PEPTIDES 2019 Customizing macromolecules through chemical ligation (#15)
The selective modification of macromolecules is a central tool of chemical biology. We have developed a suite of techniques for the chemoselective modification of unprotected macromolecules to facilitate total chemical synthesis, semisynthesis and the generation of bioconjugates. In one approach, the adaptation of well known, synthetic organic reactions to aqueous bioconjugation is facilitated through careful optimization of reaction conditions, leading to the development of novel diyne linked conjugates and macrocyclic peptides. In other work, we have developed new approaches for the C-terminal activation of proteins utilizing intramolecular reactions to provide a desired level of activation under mild reaction conditions. Finally, the reversable adsorption of macromolecules to a solid support (RASS) approach facilitates the compatibility of peptides, proteins and DNA with non-traditional reaction conditions. This approach promises to have broad utility for the chemical manipulation of macromolecules.
