CuAAC

The introductiono fm acrocyclic constraints in peptides (peptide stapling) is an important tool within pep-tide medicinalc hemistry for stabilising and pre-organising peptides in ad esired conformation.I nr ecent years, the copper-catalysed azide–alkyne cycloaddition (CuAAC) has emerged as ap owerfulm ethodf or peptidestapling. However ,t od ate CuAAC stapling has not provided as imple methodf or obtaining peptidest hat are easily diversified further .I nt he present study,w er eport an ew diversity-oriented peptides tapling (DOPS) methodology based on CuAAC chemistry.S tapling of peptides incorporating two azide-modified amino acids with 1,3,5-triethynylbenzene efficiently provides (i, i + 7)-and (i, i + 9)-stapled peptides with as ingle free alkyne positioned on the staple, which can be further conjugated or dimerised. Au nique feature of the present method is that it provides easy access to radiolabelled stapled peptidesb yc atalytic tritiation of the alkyne positioned on the staple.