Two Opposing d-Amino Acids Give Zigzag Hairpin Epitopes an Additional Kink to Create Antibody-Selective Peptide Antigens.
We have developed peptides that are able to distinguish between subgroups of polyclonal antibodies. These β-hairpin peptides act as conformational epitopes with specific shape and flexibility; they have been analyzed by NMR and CD spectroscopy, and have been shown to identify known disease markers. As a standalone mini β-sheet, a hairpin is stabilized by alternating pairs of hydrogen-bonded and non-bonded amino acids on its two opposing peptide strands. A single d mutation disrupts this secondary structure, the correlated double-d mutation of two opposing amino acids compensates for this destabilizing effect. The designed kink was introduced into both hydrogen-bonded and -non-bonded positions of an all-l hairpin that is a known conformational epitope in molecular recognition. Our peptides enabled the discrimination of different human rheumatoid arthritis autoantibodies in an ELISA assay.
Faculty of Chemistry, Philipps-Universität Marburg, Hans-Meerwein-Straßsse 4, 35032, Marburg, Germany.
Andreas
A
Schrimpf
Faculty of Chemistry, Philipps-Universität Marburg, Hans-Meerwein-Straßsse 4, 35032, Marburg, Germany.
Armin
A
Geyer
D000595:Amino Acid Sequence; D000596:Amino Acids / Q000737:chemistry / Q000378:metabolism*; D000906:Antibodies / Q000276:immunology*; D000941:Antigens / Q000737:chemistry / Q000276:immunology*; D001172:Arthritis, Rheumatoid / Q000378:metabolism / Q000473:pathology; D001323:Autoantibodies / Q000737:chemistry / Q000276:immunology; D002942:Circular Dichroism; D004797:Enzyme-Linked Immunosorbent Assay; D000939:Epitopes / Q000737:chemistry / Q000276:immunology*; D006801:Humans; D006860:Hydrogen Bonding; D009682:Magnetic Resonance Spectroscopy; D056004:Molecular Dynamics Simulation; D010455:Peptides / Q000737:chemistry* / Q000276:immunology; D017433:Protein Structure, Secondary
D000596:Amino Acids; D000906:Antibodies; D000941:Antigens; D001323:Autoantibodies; D000939:Epitopes; D010455:Peptides
ELISA; NMR spectroscopy; conformational epitopes; d-amino acids; peptides