SFB 1309
Differential Peptide Multi-Macrocyclizations at the Surface of a Helical Foldamer Template
2022-08-22
Sebastian Dengler, Céline Douat, and Ivan Huc
Angew. Chem. Int. Ed. 2022, 61, e202211138
Hybrid sequences comprising a peptide with several Cys residues and an aromatic foldamer helix with several chloroacetamide functions at its surfacewere synthesized. Such products may in principle formnumerous macromulticyclic thioether products by intra-molecularly combining all Cys residues and all chloroa-cetamide functions. However, we show that the reactivesites on the structurally defined helix can be placed atsuch locations that the peptide selectively stitches itselfto form a series of different macrocycles within mostlyone preferred product. Reactions were monitored byHPLC and products with two, three or four macrocycleswere identified using LC–MS and NMR. The series ofselective macrocyclizations define a sort of reaction trailwhere reaction sites otherwise identical are involvedsuccessively because of their precise positioning inspace. The trails can be predicted to a large extent basedon structural considerations and the assumption thatsmaller macrocycles form faster.
