Phenothiazine-Biaryl-Containing Fluorescent RGD Peptides |
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Authors: | Dr Elmira Ghabraie Dr Isabell Kemker Dr Nicolo Tonali Dr Mohamed Ismail Dr Veronica I Dodero Prof?Dr Norbert Sewald |
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Institution: | Department of Chemistry, Organic and Bioorganic Chemistry, Bielefeld University, PO Box 100131, 33501 Bielefeld, Germany |
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Abstract: | Cyclic RGD peptides are well-known ligands of integrins. The integrins αVβ3 and α5β1 are involved in angiogenesis, and integrin αVβ3 is abundantly present on cancer cells, thus representing a therapeutic target. Hence, synthetic and biophysical studies continuously are being directed towards the understanding of ligand-integrin interaction. In this context, the development of versatile synthetic strategies to obtain fluorescent building blocks that can add molecular diversity and modular spectral characteristics while not compromising binding affinity or selectivity is a relevant task. An on-resin intramolecular Suzuki–Miyaura cross-coupling (SMC) between l - or d -7-bromotryptophan (7BrTrp) and a phenothiazine (Ptz) boronic acid affords fluorescent cyclic RGD pseudopeptides, c(RGD(W/w)Ptz). Ring closure by SMC establishes a phenothiazine–indole moiety with axial chirality. An array of eight novel compounds has been synthesized, among them one fluorescent compound with good affinity to integrin αVβ3. The fluorescence properties of the analogues can be efficiently tuned depending on the substituents in Ptz moiety even for fluorescence emission in the visible (red) spectral range. |
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Keywords: | cross-coupling reactions cyclopeptides fluorescent peptide integrin phenothiazine |
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