Organometallic–Peptide Bioconjugates: Synthetic Strategies and Medicinal Applications

Abstract

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.

Reversible Covalent and Supramolecular Functionalization of Water‐Soluble Gold(I) Complexes

“…The cytotoxicity of complex 4 (IC50=26±2 μ m after 24 h, 38±2 μ m after 48 h and 41±2 μ m after 72 h) is higher than for the positive control cisplatin. This result is consistent with previously disclosed studies for water‐soluble gold(I) phosphane complexes, which reported IC50 values between 1 μ m and 100 μ m , depending on the cell line, incubation time, ligand type and lipophilicity of the gold(I) complexes …”

Metallvermittelte Funktionalisierung natürlicher Peptide und Proteine: Biokonjugation mit Übergangsmetallen

“…Mechanistische Vorschläge für diesen Prozess gibt es bereits,d och fehlt es zumeist an konkreten Belegen. [142][143][144][145][146][147] Weitere komplementäre Metallierungsansätze basieren auf der Inkorporierung [143,[148][149][150][151][152] einer nichtnatürlichen Aminosäure mit metallbindender Seitenkette (z. Obwohl sie auf eine einzige Gruppe an Funktionalisierungen beschränkt ist, hat sich die Azidgruppe zu einem essenziellen Bestandteil der gängigen Biokonjugationsmethoden entwickelt und die oben beschriebene Te chnik wurde bereits von verschiedenen Arbeitsgruppen ausführlich angewendet.…”

Synthesis and structural studies of 16‐ferrocenemethyl‐estra‐1,3,5(10)‐triene‐3,17β‐diol and its interaction with human serum albumin by fluorescence spectroscopy and in silico docking approaches

“…As a new approach to rationalize the metal‐based drug design, ferrocene has been incorporated into the principal structural component of natural and synthetic compounds with biological activity to develop more selective and effective metal‐based drugs . This approach has been applied in hormone‐dependent breast cancer, in which ferrocene has been vectorized with estrogen hormones in order to effectively deliver its moiety to cancer tissues .…”