Biological applications of amide and amino acid containing synthetic macrocycles

Anion recognition using a simple cyclic peptide

“…2 In mimicking natural anion binding systems, macrocyclic structures are of particular interest as these provide preorganised binding clefts that can adopt similar conformations to the 'nest' motif and lead to increased binding affinity and selectivity. 3 In particular, the use of cyclic peptides is of interest in this context [4][5][6] as these molecules contain the same innate binding motifs as naturally occurring peptides and proteins.…”

“…Despite the ability of naturally occurring peptides to bind to anions, the majority of investigations into anion recognition by synthetic cyclic peptides have employed highly modified peptide structures incorporating rigid backbone modifications and/or unnatural amino acids. [4][5][6][7][8] Anion binding by cyclic peptides comprising only proteinogenic amino acids is considerably less well explored, despite predictions by early computational work in the field that cyclohexaglycyl 9 and cyclohexaalanyl peptides 10 would both bind to anions through the peptide NH hydrogen bond donors. In experimental studies, the natural cyclic peptide unguisin A has been found to bind to a range of anions in acetone-d6: DMSO-d6 (9:1 v/v) 11 and the cyclic depsipeptide valinomycin has also been shown to bind to halide ions in acetone-d6 and CD3CN.…”