The Synthesis and Anti-tumour Properties of Poly Ethoxy Ethyl Glycinamide (PEE-G) Scaffolds with Multiple PD-1 Peptides Attached
| Autor: | Kathryn J. Farrand, Paul H. Teesdale-Spittle, Peter D. Mace, Rinu Shrestha, Emma V. Petley, Sam A. Jamieson, Ian F. Hermans, Wanting Jiao, Phillip M. Rendle |
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| Rok vydání: | 2020 |
| Předmět: |
Stereochemistry
Programmed Cell Death 1 Receptor Glycine Peptide Conjugated system Peptide conjugate 01 natural sciences Biochemistry Mice Structure-Activity Relationship Dendrimer Cell Line Tumor Drug Discovery Animals Humans General Pharmacology Toxicology and Pharmaceutics Pharmacology chemistry.chemical_classification Dose-Response Relationship Drug Molecular Structure 010405 organic chemistry Organic Chemistry Fluorescence Hedgehog signaling pathway 0104 chemical sciences Mice Inbred C57BL 010404 medicinal & biomolecular chemistry chemistry Alkoxy group Molecular Medicine Conjugate |
| Zdroj: | ChemMedChem. 15(13) |
| ISSN: | 1860-7187 |
| Popis: | Multivalent structures can provide multiple interactions at a target site and improve binding affinity. The multivalent presentation of the anti-tumour heptapeptide, SNTSESF, was investigated. This peptide's activity has been attributed to blockade of the PD-1 receptor-mediated signalling pathway. Two and four peptide units were conjugated to poly ethoxy ethyl glycinamide (PEE-G) scaffolds to prepare high-purity products. These conjugates and the peptide were examined in a mouse model implanted with GL261 tumours that indicated that presenting more than two copies of peptide SNTSESF on the dendritic scaffold does not increase anti-tumour activity per peptide. The fluorescent labelled peptide and most active multivalent peptide conjugate were therefore screened for their interaction with the human PD-L1 protein in a fluorescence polarisation assay. No indication of a specific SNTSESF peptide/PD-L1 interaction was observed. This finding was further supported by a molecular modelling binding study. |
| Databáze: | OpenAIRE |
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