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The substitution (Y10 P in tirzepatide) and modification (lipidated K10 P in peptide 20) stabilized the binding of dual and triple agonists by newly-formed interactions with residues surrounding the TM1-TM2 cleft, a phenomenon unseen in the case of GLP-1 27
7 There is equilibrium between free and bound drug, however, just like the relationship of ionized and nonionized drug molecules
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