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V.et al (2010)

Questions to Ask Before Anyone Injects Anything Into Your Body If a peptide is being recommended to you, the answers to the following questions tell you whether the conversation is clinical or commercial

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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