Receptor-templated stapling of intrinsically disordered peptide ligands

We report here a chemoselective peptide "stapling" method that can be performed on ligand-receptor complexes in situ. An appropriately structured macrocyclic bis-oxime linkage is shown to improve the affinity of a peptide ligand for its native protein receptor. The presence of the receptor...

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Bibliographic Details
Published inOrganic & biomolecular chemistry Vol. 13; no. 14; pp. 4183 - 4189
Main Authors Haney, Conor M., Horne, W. Seth
Format Journal Article
LanguageEnglish
Published CAMBRIDGE Royal Soc Chemistry 14.04.2015
Subjects
Amino Acid Sequence
Chemistry
Chemistry, Organic
Intrinsically Disordered Proteins - chemistry
Intrinsically Disordered Proteins - metabolism
Ligands
Models, Molecular
Molecular Sequence Data
Oximes - chemistry
Peptides - chemistry
Peptides - metabolism
Physical Sciences
Protein Conformation
Science & Technology
ALPHA-HELICAL PEPTIDES
PROTEIN INTERACTIONS
ATOMIC-STRUCTURE
HIV-1 FUSION
DESIGN
GP41
OXIME
INHIBITORS
COILED-COIL
CHAIN CROSS-LINKS
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Summary:We report here a chemoselective peptide "stapling" method that can be performed on ligand-receptor complexes in situ. An appropriately structured macrocyclic bis-oxime linkage is shown to improve the affinity of a peptide ligand for its native protein receptor. The presence of the receptor as a template to preorganize the ligand into its bioactive conformation is found to bias reaction outcomes, suggesting the potential application of the method for receptor-assisted selection of stapled peptides.
Bibliography:ObjectType-Article-1
SourceType-Scholarly Journals-1
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ISSN:1477-0520
1477-0539
DOI:10.1039/c5ob00269a