Fig. 1. (A) The trisubstituted alkene isostere with the A1,2 and A1,3 allylic strain; note the hydrophobic nature of the reverse turn. (B) N-Methylated i+2 residue at the reverse turn displaying the pseudoallylic strain pA1,3 and pA1,2 between heterochiral residues. A side view representation of pseudoallylic strain pA1,3 and pA1,2. (C) In cyclic peptides with N-methylated heterochiral residues, the trans conformation of the N-methylated amide bond is energetically more favorable than the cis conformation. (D) While, in cyclic peptides with N-methylated homochiral residues, both cis and trans conformations are energetically favorable, as observed from the solution NMR studies (ESI†).
