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Class B1 GPCRs bind their peptide agonists via a two-domain model, whereby the C-terminus of the peptide interacts with the receptor extracellular N-terminal domain (ECD) promoting an affinity trap that enables the engagement of the N-terminus of the peptide with the receptor transmembrane domain (TMD), with interactions with the TMD required for receptor activation 9

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H., Culotta, K

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Despite its high programmability, the platforms therapeutic utility was initially limited by modest in vivo performance