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Tethering of cytotoxic drugs to targeting vectors such as peptides, which recognize receptors overexpressed on the surface of tumor cells, is one possible strategy to overcome such a problem. The pentapeptide cyc(RGDfK) targets the integrin receptor \u03b1<jats:sub>v<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub>, important for tumor growth and metastasis formation. In this work, two terpyridine\u2010based Ru<jats:sup>II<\/jats:sup> complexes were prepared and for the first time conjugated to cyc(RGDfK) through amide bond formation, which resulted in a monomeric and a dimeric bioconjugate. Both Ru<jats:sup>II<\/jats:sup> complexes were found to bind strongly and selectively to integrin \u03b1<jats:sub>v<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub>, and the dimeric molecule displayed a 20\u2010fold higher affinity to the receptor than the monomeric one. However, the cytotoxicity of the complexes and related bioconjugates against human A549 and SKOV\u20103 cell lines is still not sufficient for application as anticancer agents. Nevertheless, considering the high selectivity for integrin receptor \u03b1<jats:sub>v<\/jats:sub>\u03b2<jats:sub>3<\/jats:sub>, the synthesis of Ru\u2010based bioconjugates with cyc(RGDfK) paves a promising way towards the design of effective targeted anticancer agents.<\/jats:p>","DOI":"10.1002\/ejic.201601094","type":"journal-article","created":{"date-parts":[[2016,11,10]],"date-time":"2016-11-10T13:07:50Z","timestamp":1478783270000},"page":"1667-1672","update-policy":"https:\/\/doi.org\/10.1002\/crossmark_policy","source":"Crossref","is-referenced-by-count":27,"title":["Functionalization of Ruthenium(II) Terpyridine Complexes with Cyclic RGD Peptides To Target Integrin Receptors in Cancer Cells"],"prefix":"10.1002","volume":"2017","author":[{"given":"Eva M.","family":"Hahn","sequence":"first","affiliation":[{"name":"Molecular Catalysis, Catalysis Research Center and Department of Chemistry Technische Universit\u00e4t M\u00fcnchen  Lichtenbergstr. 4 85747 Garching bei M\u00fcnchen Germany"},{"name":"School of Chemistry Cardiff University  Park Place CF103AT Cardiff United Kingdom"}]},{"given":"Natalia","family":"Estrada\u2010Ortiz","sequence":"additional","affiliation":[{"name":"Groningen Research Institute of Pharmacy University of Groningen  Antonius Deusinglaan 1 9713 AV Groningen The Netherlands"}]},{"given":"Jiaying","family":"Han","sequence":"additional","affiliation":[{"name":"Groningen Research Institute of Pharmacy University of Groningen  Antonius Deusinglaan 1 9713 AV Groningen The Netherlands"}]},{"given":"Vera F. 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