Nonconventional trans‐Platinum Complexes Functionalized with RDG Peptides: Chemical and Cytototoxicity Studies. Issue 12 (20th February 2017)

• Record Type: Journal Article
• Authors: Medrano, Maria Angeles; Morais, Maurício; Ferreira, Vera F. C.; Correia, João D. G.; Paulo, António; Santos, Isabel; Navarro‐Ranninger, Carmen; Valdes, Amparo Alvarez; Casini, Angela; Mendes, Filipa; Quiroga, Adoración G.
• Other Names: Alessio Enzo guestEditor.; Guo Zijian guestEditor.
• Is Part Of: European journal of inorganic chemistry. Issue 12(2017)
• Page Start: 1835
• Page End: 1840
• Publication Date: 2017-02-20
• Subjects: Platinum -- Peptides -- Cancer -- Cellular uptake -- αVβ3 integrin; Chemistry, Inorganic -- Periodicals; Organometallic chemistry -- Periodicals; Bioinorganic chemistry -- Periodicals; Solid state chemistry -- Periodicals; 546
• DOI: 10.1002/ejic.201700072
• Languages: English
• ISSNs: 1434-1948

Abstract

Abstract : In order for platinum complexes to target cancer cells, trans ‐Pt II or trans ‐Pt IV complexes were bioconjugated to the cyclic peptide cRGDfK (cRGD), which has an affinity for αv β3 ‐integrin receptors, through its 4‐picolinic acid spectator ligands. To tackle this goal, the Pt II and Pt IV precursors were activated at their carboxylic acid functional group, and futher treated with the cRGDfK peptide, to afford the bioconjugates Pt II –cRGD and Pt IV –cRGD, respectively. Pt II –cRGD was studied by 195 Pt NMR spectroscopy, which confirmed the presence of the Pt II center. In contrast, the characterization of Pt IV –cRGD was not possible, due to the tendency of this complex to undergo reduction to Pt II in solution. Thus, only the Pt II –cRGD complex was used for further biological studies, and it exhibited some cytotoxic activity against the HUVEC (human umbilical vein endothelial cells) cell line, which has the highest levels of αv β3 expression. However, no improved effects were observed with respect to the Pt II –pic precursor. Studies by ICP‐MS showed enhanced intracellular accumulation for Pt II –cRGD, with respect to Pt II –pic in cancer cells. Overall, these results show that, while Pt II bioconjugation enhances the uptake of the compound, it did not translate into increased cytotoxicity. Abstract : We present the conjugation of the cyclic peptide cRGDfK (cRGD) to trans ‐Pt II or trans ‐Pt IV complexes through its 4‐picolinic acid spectator ligand.