Sonogashira, CuAAC, and Oxime Ligations for the Synthesis of MnI Tricarbonyl PhotoCORM Peptide Conjugates

• Published in: European journal of inorganic chemistry Vol. 2014; no. 18; pp. 2886 - 2895
• Main Authors: Pai, Sandesh, Radacki, Krzysztof, Schatzschneider, Ulrich
• Format: Journal Article
• Language: English
• Published: Weinheim WILEY-VCH Verlag 01.06.2014; WILEY‐VCH Verlag; Wiley Subscription Services, Inc
• Subjects: Alkynes; Bioinorganic chemistry; Bioorthogonal coupling; Carbonyl ligands; CO release; Conjugates; Conjugation; Freeze thaw cycles; Growth factors; Manganese; Myoglobins; Peptides
• ISSN: 1434-1948; 1099-0682
• DOI: 10.1002/ejic.201402123

In this work, facial tricarbonylmanganese(I) complexes [Mn(bpeaCH2C6H4R)(CO)3]PF6 incorporating a functionalized 2,2‐bis(pyrazolyl)ethylamine (bpea) ligand with R = I, C≡CH, and CHO have been explored for their utility in bioorthogonal coupling to carrier peptides bearing N‐terminal alkyne, azide, and aminoxy residues. As a model system, the transforming growth factor β‐recognizing (TGF‐β) peptide sequence R′‐Leu‐Pro‐Leu‐Gly‐Asn‐Ser‐His‐OH was used in which R′ is the reactive group complementary to the metal complex functionality. The use of catalyst‐free oxime ligation gave the most stable conjugate with no degradation observed by HPLC over 96 h even after repeated freeze–thaw cycles. Both the parent complex as well as the functionalized peptide were investigated for photoactivated CO delivery to heme proteins by using the myoglobin assay and found to have essentially identical release properties. This work has established a new strategy for the conjugation of photoactivatable CO‐releasing molecules (PhotoCORMs) to biological carrier systems. Appropriately terminated peptides have been conjugated to MnI(CO)3 complexes bearing a modified bpea ligand through either a triazole or oxime linker by bioorthogonal coupling. Both the coupling methodology and bpea ligand structure are vital for successful conjugation. The peptide conjugates showed potential for the targeted delivery of CO to biological systems.