Small peptide-based GLP-1R ligands: an approach to reduce the kidney uptake of radiolabeled GLP-1R-targeting agents?

ABSTRACT:

Aim

Elevated kidney uptake in insulinoma patients remains a major limitation of radiometallated exendin-derived ligands of the glucagon-like peptide 1 receptor (GLP-1R). Based on the previously published potent GLP-1R-activating undecapeptide 1, short-chained GLP-1R ligands were developed to investigate whether kidney uptake can be reduced by means of direct ¹⁸F-labeling (nuclide-based accelerated renal excretion) or the reduction of the overall ligand charge (ligand-based reduced kidney uptake).

Materials & methods

GLP-1R ligands were prepared according to optimized standard protocols via solid-phase peptide synthesis (SPPS) or, when not practicable, via fragment coupling in solution. Synthesis of (2'-Et, 4'-OMe)4, 4'-L-biphenylalanine ((2'-Et, 4'-OMe)BIP), requi

SUBMITTER: Felber VB 

PROVIDER: S-EPMC8387526 | biostudies-literature | 2021 Aug

REPOSITORIES: biostudies-literature