The Diels-Alder reaction between diene-modified oligonucleotides and maleimide-derivatized peptides afforded peptide-oligonucleotide conjugates with high purity and yield. Synthesis of the reagents was easily accomplished by on-column derivatization of the corresponding peptides and oligonucleotides. The cycloaddition reaction was carried out in mild conditions, in aqueous solution at 37 degrees C. The speed of the reaction was found to vary depending on the size of the reagents, but it can be completed in 8-10 h by reacting the diene-oligonucleotide with a small excess of maleimide-peptide.

Finding alternatives to gadolinium (Gd)-based contrast agents (CA) with the same or even better paramagnetic properties is crucial to overcome their established toxicity. Herein we describe the synthesis and characterization of entirely organic metal-free paramagnetic macromolecules based on biocompatible oligoethylene glycol dendrimers fully functionalized with 5 and 20 organic radicals (OEG Gn-PROXYL (n = 0, 1) radical dendrimers) with the aim to be used as magnetic resonance imaging (MRI) contrast agents. Conferring high water solubility on such systems is often a concern, especially in large generation dendrimers. Our approach to overcome such an issue in this study is by synthesizing dendrimers with highly water-soluble branches themselves. In this work, we show that the highly water-soluble OEG Gn-PROXYL (n = 0, 1) radical dendrimers obtained showed properties that convert them in good candidates to be studied as contrast agents for MRI applications like diagnosis and follow-up of infectious diseases, among others. Importantly, with the first generation radical dendrimer, a similar r₁ relaxivity value (3.4 mM⁻¹s⁻¹) in comparison to gadolinium-diethylenetriamine pentaacetic acid (Gd-DTPA) used in clinics (3.2 mM⁻¹s⁻¹, r.t. 7T) has been obtained, and it has been shown to not be cytotoxic, avoiding the toxicity risks associated with the unwanted accumulation of Gd in the body.