Multifunctional α <sub>v</sub>β <sub>6</sub> Integrin-Specific Peptide-Pt(IV) Conjugates for Cancer Cell Targeting
- Author(s)
- Anne C. Conibear, Sonja Hager, Josef Mayr, Matthias H. M. Klose, Bernhard K. Keppler, Christian R. Kowol, Petra Heffeter, Christian F. W. Becker
- Abstract
Increasing the specificity of cancer therapy, and thereby decreasing damage to normal cells, requires targeting to cancer-cell specific features. The α
vβ
6 integrin is a receptor involved in cell adhesion and is frequently up-regulated in cancer cells compared to normal cells. We have selected a peptide ligand reported to bind specifically to the β
6 integrin and have synthesized a suite of multispecific molecules to explore the potential for targeting of cancer cells. A combination of solid-phase peptide synthesis and chemoselective ligations was used to synthesize multifunctional molecules composed of integrin-targeting peptides, cytotoxic platinum(IV) prodrugs, and fluorescent or affinity probes joined with flexible linkers. The modular synthesis approach facilitates the construction of peptide-drug conjugates with various valencies and properties in a convergent manner. The binding and specificity of the multifunctional peptide conjugates were investigated using a cell line transfected with the β
6 integrin and fluorescence microscopy. This versatile and highly controlled approach to synthesizing labeled peptide-drug conjugates has the potential to target potent cytotoxic drugs specifically to cancer cells, reducing the doses required for effective treatment.
- Organisation(s)
- Department of Biological Chemistry, Department of Inorganic Chemistry
- External organisation(s)
- Medizinische Universität Wien
- Journal
- Bioconjugate Chemistry
- Volume
- 28
- Pages
- 2429-2439
- No. of pages
- 11
- ISSN
- 1043-1802
- DOI
- https://doi.org/10.1021/acs.bioconjchem.7b00421
- Publication date
- 09-2017
- Peer reviewed
- Yes
- Austrian Fields of Science 2012
- 301904 Cancer research, 106002 Biochemistry, 106023 Molecular biology
- Keywords
- ASJC Scopus subject areas
- Bioengineering, Biotechnology, Biomedical Engineering, Pharmacology, Pharmaceutical Science, Organic Chemistry
- Sustainable Development Goals
- SDG 3 - Good Health and Well-being
- Portal url
- https://ucrisportal.univie.ac.at/en/publications/c5052ef4-e4fb-468a-b7c2-75dfc1b5bf72