Catalyst-free site-selective cross-aldol bioconjugations

Abstract

The bioconjugation of proteins to small molecules serves as an invaluable tool for probing biological mechanisms and creating biomaterials. The most powerful bioconjugation stratagems are those which have rapid kinetics, are site-selective, can be conducted in aqueous solvent under mild conditions and do not require the use of additional potentially toxic catalysts. Herein we present spontaneous coupling via aldol ligation of proteins (SCALP) a catalyst-free “green” site-selective protein ligation between α-oxo aldehyde functionalised proteins and enolisable aldehyde probes at neutral pH, and demonstrate the utility of this system in the targeting of prostate cancer cells with functionalised nanobodies.

Preparation and Application of an Inexpensive α-Formylglycine Building Block Compatible with Fmoc Solid-Phase Peptide Synthesis

“…We demonstrate that this building block is compatible with conventional and microwave-assisted SPPS, and prepare the pharmaceuticallyrelevant peptide Callyaerin A, a potent anti-tuberculosis macrocyclic peptide which contains a (Z)-2,3-diaminoacrylamide moiety derived from an fGly residue inaccessible to FGE/anSME-based enzymatic efforts. [9d, 10] Oxidative cleavage of 1,2-diols [11] or 1,2-amino alcohols [12] using periodate is a mild and commonly-used method for the installation of aldehydes into biomolecules. 1,2-diols presented on the side-chains of sialic acids are highly susceptible to periodate oxidation, [11] yet are tolerant to the conditions required for resin cleavage after SPPS.…”