Organometallic-Peptide Bioconjugates: Synthetic Strategies and Medicinal Applications.

Peptides are important biological molecular entities in biomedical research. They can be prepared in a large variety of shapes, with a host of chemical functions, and tailored for specific applications. Organometallic medicinal chemistry is a relatively young field that explores biomedical and bioanalytical applications of organometallic complexes, that is, metal compounds with at least one direct, covalent metal-carbon bond. The conjugation of peptides to such medicinally active organometallic moieties started only about 20 years ago, and it has been very beneficial for the development of bioorganometallic chemistry in general. Similarly, the biomedical properties of peptides have been altered by their conjugation to organometallic (OM) moieties. In this review, synthetic methods by which OM moieties can be conjugated to peptides via a carbon-metal bond are described, and selected medicinal applications of such conjugates are discussed. Inorganic coordination complexes between metal ions and peptides are excluded from this review. Also, the labeling of peptides with radiometals and applications of radiolabeled peptides will not be treated herein. First, modifications of the peptide backbone (either N- or C-terminally, or both) with organometallic moieties will be described, including the insertion of OM moieties as part of the peptide backbone. Then side-chain modifications will be reported, among them the most recent strategies for chemoselective arene metalation on peptides. Finally, approaches by which multiple metalation can be achieved are explored. In each section, selected examples of biological applications are highlighted.