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The published account describes an optimization campaign across acyl-chain lengths, linker chemistries, and amino-acid substitutions, converging on a molecule with three defining modifications relative to native GLP-1(7-37): Position 8 (Ala to Aib): substitution of alanine with alpha-aminoisobutyric acid, a non-natural amino acid that sterically blocks DPP-4 cleavage at the N-terminus, directly answering the 1995 degradation finding
Moreover, GLP-1 could be involved in mechanisms of growth and expansion of IECs, as the loss of GLP-1Rs on IELs has been associated with shorter and smaller intestines in mice (59, 63, 64)
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