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Tirzepatide features a tyrosine at its Nterminus, which is typically required for high GIP receptor affinity but was also shown previously to attenuate GLP1 receptor arrestin recruitment efficacy as part of an exploration of exendin4 Nterminal substitutions (Jones, Bloom, et al., 2018)

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doi: 10.1111/imm.13443 89 MoritaSTakagiTInabaHFurukawaYKishimotoSUrakiSet al