Lighting up the PEGylation agents via the Hantzsch reaction

Fluorescent PEGylation agents have been facilely synthesized through the Hantzsch reaction. Different from other methods, a protein reactive group has been linked at the PEG chain ends through a Hantzsch ester, which is inherently fluorescent, to in situ generate fluorescent protein-reactive PEGs. Therefore, after conjugation with a protein, the multifunctional polymers can not only act as a protective umbrella to the protein like normal PEGylation agents, but also introduce new functions to the protein conjugates to achieve multifunctional protein conjugates. The multifunctional protein conjugates are directly visible under UV and retain nearly intact bioactivity, preliminarily suggesting the new application of the 'old' Hantzsch reaction in other areas (polymer chemistry, chemical biology) outside organic chemistry.