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- W2805265242 abstract "The isoDGR sequence is an integrin-binding motif that has been successfully employed as a tumor-vasculature-homing molecule or for the targeted delivery of drugs and diagnostic agents to tumors. In this context, we previously demonstrated that cyclopeptide 2, the product of the conjugation of c(CGisoDGRG) (1) to 4-(N-maleimidomethyl)cyclohexane-1-carboxamide, can be successfully used as a tumor-homing ligand for nanodrug delivery to neoplastic tissues. Here, combining NMR, computational, and biochemical methods, we show that the succinimide ring contained in 2 contributes to stabilizing interactions with αvβ3, an integrin overexpressed in the tumor vasculature. Furthermore, we demonstrate that various cyclopeptides containing the isoDGR sequence embedded in different molecular scaffolds do not induce αvβ3 allosteric activation and work as pure integrin antagonists. These results could be profitably exploited for the rational design of novel isoDGR-based ligands and tumor-targeting molecules with improved αvβ3-binding properties and devoid of adverse integrin-activating effects." @default.
- W2805265242 created "2018-06-13" @default.
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- W2805265242 date "2018-06-08" @default.
- W2805265242 modified "2023-10-17" @default.
- W2805265242 title "Succinimide-Based Conjugates Improve IsoDGR Cyclopeptide Affinity to α<sub>v</sub>β<sub>3</sub> without Promoting Integrin Allosteric Activation" @default.
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- W2805265242 doi "https://doi.org/10.1021/acs.jmedchem.8b00745" @default.
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