Buschmann, Jonas and Seiler, Theresa and Bernhardt, Guenther and Keller, Max and Wifling, David (2020) Argininamide-type neuropeptide Y Y-1 receptor antagonists: the nature of N-omega-carbamoyl substituents determines Y1R binding mode and affinity. RSC MEDICINAL CHEMISTRY, 11 (2). pp. 274-282. ISSN , 2632-8682
Full text not available from this repository. (Request a copy)Abstract
The recently resolved crystal structure of the neuropeptide Y Y-1 receptor (Y1R), co-crystallized with the high-affinity (pK(i): 10.11), argininamide-type Y1R antagonist UR-MK299 (2), revealed that the N-omega-carbamoyl substituent (van der Waals volume: 139 angstrom(3)) is deeply buried in the receptor, occupying a hydrophobic pocket. We synthesized and characterized a series of argininamides, structurally related to 2. Y1R affinity decreased with increasing size of the carbamoyl residue (minimal pK(i): 5.67). Exceeding a critical size of the substituent (van der Waals volume: 212 angstrom(3)), the ligands bound in an inverted mode with the carbamoyl side chain located at the surface of the receptor, as suggested by induced-fit docking and MD simulations.
| Item Type: | Article |
|---|---|
| Uncontrolled Keywords: | HIGHLY POTENT; FLUORESCENT; PEPTIDE; DESIGN; CANCER; |
| Subjects: | 600 Technology > 615 Pharmacy |
| Divisions: | Chemistry and Pharmacy > Institute of Pharmacy Chemistry and Pharmacy > Institute of Pharmacy > Alumni or Retired Professors > Pharmaceutical/Medicinal Chemistry II (Prof. Buschauer) |
| Depositing User: | Dr. Gernot Deinzer |
| Date Deposited: | 31 Mar 2021 06:55 |
| Last Modified: | 31 Mar 2021 06:55 |
| URI: | https://pred.uni-regensburg.de/id/eprint/45170 |
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