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Here we report the design and preclinical evaluation of a unimolecular quintuple agonist, which via covalent binding of Lani to a GLP-1RGIPR co-agonist allows for its targeted delivery into cells that express the receptor for GLP-1 or GIP

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Endosomal binding CHO-SNAP-GLP-1R cells were labeled with 5 M BG-SS-biotin, a cleavable SNAP-Surface probe containing a disulfide bond between O 6 -benzylguanine and biotin moieties (a gift from New England Biolabs) plus streptavidin-terbium cryptate (Cisbio, 0.24 g ml 1 active moiety)

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