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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

4.6 Closing remarks According to the ACLM ( Eating healthy food before taking medication (i.e., Food over Medicine), and continuously linked to Moderate-to-high levels of day-to-day PA, sports, and exercise (i.e., Exercise over Medicine)

Physiology, Proteins