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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
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Tirzepatide activates GIP and GLP-1 receptors in the body that control hunger and satiety signals
These simulations showed that the linker-lipid chain of semaglutide wraps around the peptide alpha-helix and produces a helical structure with an average molecular radius (including the peptide, linker and lipid) that falls in the same range as that required in the pharmacokinetic model
