| Affiliation: | 1. ARC Centre of Excellence for Nanoscale Biophotonics (CNBP), University of Adelaide, Adelaide, SA 5005 Australia;2. The Institute for Photonics & Advanced Sensing (IPAS), University of Adelaide, Adelaide, SA 5005 Australia School of Biological Sciences, University of Adelaide, Adelaide, SA 5005 Australia;3. Department of Chemistry, University of Adelaide, Adelaide, SA 5005 Australia;4. The Institute for Photonics & Advanced Sensing (IPAS), University of Adelaide, Adelaide, SA 5005 Australia |
| Abstract: | An 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. |
