General dual functionalisation of biomacromolecules via a cysteine bridging strategy. Issue 22 (20th May 2020)

• Record Type: Journal Article
• Authors: Walsh, Stephen J.; Iegre, Jessica; Seki, Hikaru; Bargh, Jonathan D.; Sore, Hannah F.; Parker, Jeremy S.; Carroll, Jason S.; Spring, David R.
• Is Part Of: Organic & biomolecular chemistry. Volume 18:Issue 22(2020)
• Page Start: 4224
• Page End: 4230
• Publication Date: 2020-05-20
• Subjects: Chemistry, Organic -- Periodicals; Bioorganic chemistry -- Periodicals; Chemistry, Physical organic -- Periodicals; 547
• DOI: 10.1039/d0ob00907e
• Languages: English
• ISSNs: 1477-0520

Abstract

Abstract : A general method that facilitates the modular dual functionalisation of a range of peptides and proteins is reported. Abstract : Site-selective modification of peptides and proteins has resulted in the development of a host of novel tools for the study of cellular systems or the synthesis of enhanced biotherapeutics. There is a need for useful methodologies that enable site-selective modification of native peptides or proteins, which is even more prevalent when modification of the biomolecule with multiple payloads is desired. Herein, we report the development of a novel dual functional divinylpyrimidine (dfDVP) platform that enables robust and modular modification of peptides, antibody fragments and antibodies. These biomacromolecules could be easily functionalised with a range of functional payloads ( e.g. fluorescent dyes, cytotoxic warheads or cell-penetrating tags). Importantly, the dual functionalised peptides and antibodies demonstrated exquisite bioactivity in a range of in vitro cellular assays, showcasing the enhanced utility of these bioactive conjugates.