RESUMEN
A class of Gd(III) coiled coils achieve high MRI relaxivity, in part due to their slow rotational correlation time. However, extending their length is unable to further enhance performance, as the mechanism by which relaxivity is achieved is dominated by the presence of three inner sphere waters in rapid exchange, through an associative mechanism.
RESUMEN
Herein are discussed a selection of lanthanide peptide/protein complexes in view of their potential applications as imaging agents, both in terms of luminescence detection and magnetic resonance imaging. Though this chapter covers a range of different peptides and protein, if focuses specifically on the opportunities afforded by the de novo design of coiled coils, miniature protein scaffolds, and the development on lanthanide-binding sites into these architectures. The requirements for lanthanide coordination and the challenges that need to be addressed when preparing lanthanide peptides with a view to their potential adoption as clinical imaging applications, will be highlighted.
Asunto(s)
Medios de Contraste/química , Elementos de la Serie de los Lantanoides/química , Péptidos/química , Proteínas/química , Secuencia de Aminoácidos/genética , Sitios de Unión , Medios de Contraste/síntesis química , Elementos de la Serie de los Lantanoides/síntesis química , Luminiscencia , Imagen por Resonancia Magnética , Péptidos/síntesis química , Proteínas/síntesis químicaRESUMEN
We have compared the organometallic arene complexes [(eta(6)-biphenyl)M(ethylenediamine)Cl](+) RM175 (M=Ru(II)) and its isostructural osmium(II) analogue AFAP51 (M=Os(II)) for their ability to induce cell detachment resistance from fibronectin, collagen IV and poly-l-lysine, and cell re-adhesion after treatment, their effects on cell migration and cell viability, on matrix metalloproteinases production, and on primary tumour growth of MCa mammary carcinoma, the effect of human serum albumin on their cytotoxicity. There are differences between ruthenium and osmium. The Os complex is up to 6x more potent than RM175 towards highly-invasive breast MDA-MB-231, human breast MCF-7 and human epithelial HBL-100 cancer cells, but whereas RM175 was active against MCa mammary carcinoma in vivo and caused metastasis reduction, AFAP51 was not. Intriguingly the presence of human serum albumin in the growth medium enhanced the cytotoxicity of both compounds. RM175 increased the resistance of MDA-MB-231 cells to detachment from substrates and both compounds inhibited the production of MMP-2. These data confirm the key role of ruthenium itself in anti-metastatic activity. It will be interesting to explore the activity of osmium arene complexes in other tumour models and the possibility of changing the non-arene ligands to tune the anticancer activity of osmium in vivo.