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Approaches to Introduce Helical Structure in Cysteine‐Containing Peptides with a Bimane Group
Author(s) -
Horsfall Aimee J.,
McDougal Daniel P.,
Scanlon Denis B.,
Bruning John B.,
Abell Andrew D.
Publication year - 2021
Publication title -
chembiochem
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.05
H-Index - 126
eISSN - 1439-7633
pISSN - 1439-4227
DOI - 10.1002/cbic.202100241
Subject(s) - peptide , chemistry , residue (chemistry) , linker , stereochemistry , cysteine , alanine , tryptophan , crystallography , amino acid , biochemistry , computer science , enzyme , operating system
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 3 10 ‐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.