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  • The general process for preparing maleimido-oligonucleotide derivatives is regioselective and automatable.
  • Incorporation of the maleimide precursor takes place in high yield, and allows high purity maleimido-oligonucleotides and oligonucleotide conjugates to be obtained.


The group is looking for a license, but other collaborations may be considered.


A priority patent application was filed to protect the new intermediate compound and the process for solid-phase preparation of the maleimido-oligonucleotide derivative.




Inma Íñiguez. Tel: +34 93 403 97 98
Email: iiniguez@fbg.ub.es.
Web: www.fbg.ub.es

Executive summary

A research group, with wide experience in the chemistry of oligonucleotides, has developed a new method for the solid-phase preparation of maleimide-oligonucleotide derivatives that is more efficient and straightforward than the currently available methods.
The research group is looking for license agreement, but other collaborations may be considered (e.g. financial resources, etc.).


At present there is a great interest in identifying and developing oligonucleotides, which are useful in therapy and diagnostics, and in nanotechnology.
For these applications, there are some limitations associated with the targeting to the specific cell, transport across the cell membrane and oligonucleotide stability that are overcome with the conjugation of the oligonucleotides with specific molecules.

There are numerous protocols to carry out the conjugation of a molecule to an oligonucleotide, and some of them include the derivatization of the oligonucleotide with the maleimide as a functional group. This allows the subsequent conjugation of agents including a thiol or a diene.


To date the processes to prepare maleimide-oligonucleotide derivatives take place in solution and show regioselectivity problems, resulting in low yield and purity of the derivatives. This affects the subsequent steps wherein the oligonucleotide is conjugated to the molecule of interest, obtaining the target conjugate in much lower yield.

The inventors have developed a general process for assembling maleimide-oligonucleotide derivatives on a solid matrix.
This process requires the design and use of a new key intermediate, in order to carry out the derivatization with the maleimide avoiding secondary reactions.

Moreover, this new intermediate has permitted to work in mild conditions, minimizing the risk of degradation of the oligonucleotide.

The reactions have been carried out at the micromolar scale for optimization of reaction conditions.


Current stage of development

The process is available for demonstration.



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Tags: Life Sciences, Salud y ciencias de la vida


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