PMID: 11606135Oct 19, 2001Paper

Utility of azapeptides as major histocompatibility complex class II protein ligands for T-cell activation

Journal of Medicinal Chemistry
M Hart, C Beeson

Abstract

Major histocompatibility complex class II (MHC II) protein binding and antigen specific activation of CD4+ "helper" T cells are demonstrated with peptides composed of the antigenic hen egg ovalbumin 325-339 peptide (OVA) substituted with azaamino acids. AzaAla and azaGly substitutions were made at 10 sequential peptide positions (326Ala-335Asn) that lie in the binding groove. The peptide positions substituted with azaamino acids encompass almost the entire binding groove, including positions where the identity of the amino acid side chain is known to have the most significant effect on MHC binding and the least effect on T-cell recognition. In addition, the T-cell contact 333Glu was substituted with azaGlu to generate a partial agonist ligand for the 3DO-54.8 T-cell hybridoma. Binding to MHC II protein was assayed by measuring the kinetic stability of complexes formed between detergent-solubilized MHC II I-A(d) protein and fluorescein-labeled OVA peptides using a fluorescence-HPLC assay. T-cell activation was also evaluated for aza-substituted peptides with azaamino acid substitutions at the peptide positions known to interact with the MHC II protein. All aza-substituted peptides showed detectable MHC binding, and some were fou...Continue Reading

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Citations

Feb 22, 2002·Medicinal Research Reviews·Benjamin J McFarland, Craig Beeson
Dec 10, 2002·Current Opinion in Chemical Biology·James A Patch, Annelise E Barron
Aug 3, 2011·Future Medicinal Chemistry·Caroline ProulxWilliam D Lubell
Jan 30, 2014·Drug Delivery·Narayanan KasinathanJ Venkata Rao
Jun 10, 2017·Accounts of Chemical Research·Ramesh ChingleWilliam D Lubell
Aug 6, 2005·American Journal of Medical Genetics. Part a·Debra J H MathewsKathy Hudson
Sep 11, 2017·Molecular Neurobiology·Nicole N M TragerCraig C Beeson
Feb 22, 2011·Expert Review of Vaccines·Nathan P Croft, Anthony W Purcell
Aug 9, 2019·The Journal of Immunology : Official Journal of the American Association of Immunologists·Ross W ChelohaHidde L Ploegh
Oct 3, 2002·Journal of the American Chemical Society·Ho-Jin LeeKang-Bong Lee

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