For those scientists that frequently have to conjugate Oligonucleotides to proteins it is always important to have a procedure for efficient activation of the Oligonucleotide. Usually it is done with Bifunctional cross-linker because maleimide functionality cannot be introduced directly during the solid-phase oligonucleotide synthesis,
But work from Dr. Kurt V. Gothelf at the Aarhus University allows scientist to turn their Amine-functionalized oligos without the use of cross-linker. Maleimide functionality is formed directly on the existing amino-Oligo.
They used N-methoxycarbonylmaleimide to turn Oligo into Maleimide within 30-60min under alkalyne conditions. Efficiency of this reaction is somparable to the use of SMCC.
More about the method could be read here: https://pubs.acs.org/doi/pdf/10.1021/acs.bioconjchem.2c00144