Photoactive platinum(iv) complex conjugated to a cancer-cell-targeting cyclic peptide.

Abstract

A conjugate of cancer-cell targeting cyclic disulphide nona-peptide c(CRWYDENAC) consisting of nine l-amino acids with the photoactive succinate platinum(iv) complex trans,trans-[Pt(N3)2(py)2(OH)(succinate)] (Pt-cP) has been synthesised and characterised. The conjugate was stable in dark, but released succinate-peptide and Pt(ii) species upon irradiation with visible light, and formed photoproducts with guanine. Conjugate Pt-cP exhibited higher photocytotoxicity than parent complex trans,trans,trans-[Pt(N3)2(OH)2(py)2] (FM-190) towards cancer cells, including ovarian A2780, lung A549 and prostate PC3 human cancer cells upon irradiation with blue light (465 nm, 17.28 J cm-2) with IC50 values of 2.8-22.4 μM and the highest potency for A549 cells. Even though the dark cellular accumulation of Pt-cP in A2780 cells was lower than that of parent FM-190, Pt from Pt-cP accumulated in cancer cells upon irradiation to a level >3× higher than that from FM-190. In addition, the cellular accumulation of Pt from Pt-cP was enhanced ca. 47× after irradiation.

• Authors: Huayun Shi, Qian Wang, V Venkatesh, Guokai Feng, Lawrence S Young, Isolda Romero-Canelón, Musheng Zeng, Peter J Sadler
• Journal: Dalton transactions (Cambridge, England : 2003) (Dalton Trans) Vol. 48 Issue 24 Pg. 8560-8564 (Jun 28 2019) ISSN: 1477-9234 [Electronic] England
• PMID: 31147656 (Publication Type: Journal Article)

Chemical References

• Antineoplastic Agents
• Organoplatinum Compounds
• Peptides, Cyclic

Topics

• Antineoplastic Agents (chemistry, pharmacology)
• Cell Line, Tumor
• Humans
• Inhibitory Concentration 50
• Light
• Organoplatinum Compounds (chemistry, pharmacology)
• Peptides, Cyclic (chemistry)