Matches in SemOpenAlex for { <https://semopenalex.org/work/W4387300084> ?p ?o ?g. }
- W4387300084 abstract "Receptor-selective peptides are widely used as smart carriers for specific tumor-targeted delivery. A remarkable example is the cyclic nonapeptide iRGD (CRGDKPGDC, 1) that couples intrinsic cytotoxic effects with striking tumor-homing properties. These peculiar features are based on a rather complex multistep mechanism of action, where the primary event is the recognition of RGD integrins. Despite the high number of preclinical studies and the recent success of a phase I trial for the treatment of pancreatic ductal adenocarcinoma (PDAC), there is little information available about the iRGD three-dimensional (3D) structure and integrin binding properties. Here, we re-evaluate the peptide’s affinity for cancer-related integrins including not only the previously known targets αvβ3 and αvβ5 but also the αvβ6 isoform, which is known to drive cell growth, migration, and invasion in many malignancies including PDAC. Furthermore, we use parallel tempering in the well-tempered ensemble (PT-WTE) metadynamics simulations to characterize the in-solution conformation of iRGD and extensive molecular dynamics calculations to fully investigate its binding mechanism to integrin partners. Finally, we provide clues for fine-tuning the peptide’s potency and selectivity profile, which, in turn, may further improve its tumor-homing properties." @default.
- W4387300084 created "2023-10-04" @default.
- W4387300084 creator A5008036169 @default.
- W4387300084 creator A5013228218 @default.
- W4387300084 creator A5020145204 @default.
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- W4387300084 creator A5041407933 @default.
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- W4387300084 creator A5073093302 @default.
- W4387300084 creator A5081381092 @default.
- W4387300084 creator A5082554755 @default.
- W4387300084 date "2023-10-03" @default.
- W4387300084 modified "2023-10-05" @default.
- W4387300084 title "Molecular View on the <i>i</i>RGD Peptide Binding Mechanism: Implications for Integrin Activity and Selectivity Profiles" @default.
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