Horsfall, A.J.McDougal, D.P.Scanlon, D.B.Bruning, J.B.Abell, A.D.2021-07-302021-07-302021ChemBioChem, 2021; 22(17):2711-27201439-42271439-7633http://hdl.handle.net/2440/131378First published: 09 June 2021An i-i+4 or i-i+3 bimane-containing linker was introduced into a peptide known to target Estrogen Receptor alpha (ERα) in order to stabilise an α-helical geometry. These macrocycles were studied by CD and NMR to reveal the i-i+4 constrained peptide adopts a 310-helical structure in solution, and an α-helical conformation on interaction with the ERα coactivator recruitment surface in silico. An acyclic bimane-modified peptide is also helical, when it includes a tryptophan or tyrosine residue; but is significantly less helical with a phenylalanine or alanine residue, which indicates such a bimane modification influences peptide structure in a sequence dependent manner. The fluorescence intensity of the bimane appears influenced by peptide conformation, where helical peptides displayed a fluorescence increase when TFE was added to phosphate buffer, compared to a decrease for less helical peptides. This study presents the bimane as a useful modification to influence peptide structure as an acyclic peptide modification, or as a side-chain constraint to give a macrocycle.en© 2021 Wiley-VCH GmbHBimaneHelical structuresPeptidomimeticsfluorescencepeptidesJournal article100004216110.1002/cbic.2021002410006647974000012-s2.0-85108379104578140Horsfall, A.J. [0000-0003-1276-2742]McDougal, D.P. [0000-0003-4499-6789]Bruning, J.B. [0000-0002-6919-1824]Abell, A.D. [0000-0002-0604-2629]