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Notably 16 , devoid of a macrocyclic ring system in the N-terminal is not selective and inhibits both IRAP and AP-N activity, suggesting that introduction of proper conformational constrains in the N-terminal by macrocyclization improves selectivity (Axn et al., 2007)

An unusually cheap product is usually underdosed, impure, or both

Women using oral contraceptives should be advised that tirzepatide may reduce contraceptive effectiveness due to delayed gastric emptying

10.1016/j.jtos.2019.10.006 280 TsementziD.PenaGonzalezA.BaiJ.HuY

This approach inspired other programmes: N-hexanoic-Tyr-D-Arg : enkephalin-derived, protease-resistant, studied for pain N-methyl-Aib inclusions : N-methyl substitutions increase membrane permeability at the cost of partial loss of receptor affinity Beta-peptides and D-amino acids : substitution of natural chiral residues by their D enantiomers, making the peptide invisible to endogenous proteases while (sometimes) preserving function Stapled peptides : hydrocarbon cyclisation, popularised by Verdine (Harvard), stabilises alpha helices and improves cellular penetration These strategies progressively shift the peptide / small molecule frontier