The Synthesis and Anti-tumour Properties of Poly Ethoxy Ethyl Glycinamide (PEE-G) Scaffolds with Multiple PD-1 Peptides Attached.

The Synthesis and Anti-tumour Properties of Poly Ethoxy Ethyl Glycinamide (PEE-G) Scaffolds with Multiple PD-1 Peptides Attached.
ChemMedChem. 2020 May 12;:
Authors: Shrestha R, Petley EV, Farrand KJ, Jamieson SA, Jiao W, Teesdale-Spittle PH, Hermans IF, Mace PD, Rendle PM
Abstract
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 which 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 via a fluorescence polarization assay. No indication of a specific SNTSESF peptide/PD-L1 interaction was observed. This finding was further supported by a molecular modelling binding study.
PMID: 32400116 [PubMed - as supplied by publisher]

Source: ChemMedChem - May 11, 2020 Category: Chemistry Authors: Shrestha R, Petley EV, Farrand KJ, Jamieson SA, Jiao W, Teesdale-Spittle PH, Hermans IF, Mace PD, Rendle PM Tags: ChemMedChem Source Type: research