Approaches to introduce helical structure in cysteine-containing peptides with a bimane group

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dc.contributor.authorHorsfall, A.J.
dc.contributor.authorMcDougal, D.P.
dc.contributor.authorScanlon, D.B.
dc.contributor.authorBruning, J.B.
dc.contributor.authorAbell, A.D.
dc.date.issued2021
dc.descriptionFirst published: 09 June 2021
dc.description.abstractAn 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.
dc.description.statementofresponsibilityAimee J. Horsfall, Daniel P. McDougal, Denis B. Scanlon, John B. Bruning, Andrew D. Abell
dc.identifier.citationChemBioChem, 2021; 22(17):2711-2720
dc.identifier.doi10.1002/cbic.202100241
dc.identifier.issn1439-4227
dc.identifier.issn1439-7633
dc.identifier.orcidHorsfall, A.J. [0000-0003-1276-2742]
dc.identifier.orcidMcDougal, D.P. [0000-0003-4499-6789]
dc.identifier.orcidBruning, J.B. [0000-0002-6919-1824]
dc.identifier.orcidAbell, A.D. [0000-0002-0604-2629]
dc.identifier.urihttp://hdl.handle.net/2440/131378
dc.language.isoen
dc.publisherWiley
dc.relation.granthttp://purl.org/au-research/grants/arc/CE140100003
dc.rights© 2021 Wiley-VCH GmbH
dc.source.urihttps://doi.org/10.1002/cbic.202100241
dc.subjectBimane
dc.subjectHelical structures
dc.subjectPeptidomimetics
dc.subjectfluorescence
dc.subjectpeptides
dc.titleApproaches to introduce helical structure in cysteine-containing peptides with a bimane group
dc.typeJournal article
pubs.publication-statusPublished

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