Bioconjugation is the covalent linkage of two chemically distinct moieties in which at least one is a biologic. This is a facile and effective chemistry approach to achieve new molecular characteristics and synergistic properties. Probably the paradigm of this technique has been the development of Antibodies Drug Conjugates (ADC) in the field of cancer therapy. However, Peptides Drug Conjugates (PDC) are being also developed for fighting cancer and other important diseases.<br/>As the two molecules to be conjugated have been already showed independently its biological activity, the cornerstone of ADC/PDC is the linker. An analysis of the literature shows that the most part if chimeras has a bifunctional maleimido linker, which incorporates one of the two moieties via a thiol function through a Michael reaction. However, this kind of compound is susceptible to retro-Michael reactions with the consequent deconjugation– a process that causes the drug to be released before reaching the target, and jeopardizes the all process .<br/>In this presentation, we will describe different bi- and tri-orthogonal linkers developed in our laboratory for bioconjugation. Different chemistries have been used which confer selectivity and diversity.<br/>The idea behind of the trifunctional ones is doubling the payload, if required, attaching two different drugs, and more important to incorporate some moieties, such as (mini)PEGs, sugars, or others to overcome the problems associated with the extreme hydrophobicity of the payloads.

Bi- and tri-orthogonal linkers for bioconjugation

255th National Meeting (2018)

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