Approaches to Introduce Helical Structure in Cysteine‐Containing Peptides with a Bimane Group

• DOI: 10.1002/cbic.202100241
• Publication Date: 2021-06-09T20:11:25Z
• Authors: Aimee J. Horsfall; Daniel P. McDougal; Denis B. Scanlon; John B. Bruning; Andrew D. Abell
• Keywords: Residue (chemistry); Linker; Alanine

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 stabilise an α-helical geometry. These macrocycles were studied by CD and NMR reveal the constrained adopts 310 -helical structure solution, conformation on interaction with ERα coactivator recruitment surface silico. acyclic bimane-modified is also helical, when it includes tryptophan tyrosine residue; but significantly less helical phenylalanine alanine residue, which indicates such bimane modification influences sequence dependent manner. The fluorescence intensity of appears influenced conformation, where peptides displayed increase TFE added phosphate buffer, compared decrease for peptides. This study presents as useful influence modification, side-chain constraint give macrocycle.