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

ChemMedChem. 2020 Jul 3;15(13):1128-1138. doi: 10.1002/cmdc.202000221. Epub 2020 Jun 2.


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.

Keywords: PD-1; PD−L; dendrimers; fluorescence polarisation; peptide conjugate.

Publication types

  • Research Support, Non-U.S. Gov't