title: Structure-Activity Relationship Studies, SPR Affinity Characterization, and Conformational Analysis of Peptides That Mimic the HNK-1 Carbohydrate Epitope.
abstract: The design of molecules that mimic biologically relevant glycans is a significant goal for understanding important biological processes and may lead to new therapeutic and diagnostic agents. In this study we focused our attention on the trisaccharide human natural killer cell-1 (HNK-1), considered the antigenic determinant of myelin-associated glycoprotein and the target of clinically relevant auto-antibodies in autoimmune neurological disorders such as IgM monoclonal gammopathy and demyelinating polyneuropathy. We describe a structure-activity relationship study based on surface plasmon resonance binding affinities aimed at the optimization of a peptide that mimics the HNK-1 minimal epitope. We developed a cyclic heptapeptide that shows an affinity of 1.09×10-7m for a commercial anti-HNK1 mouse monoclonal antibody. Detailed conformational analysis gave possible explanations for the good affinity displayed by this novel analogue, which was subsequently used as an immunological probe. However, preliminary screening indicates that patients' sera do not specifically recognize this peptide, showing that murine monoclonal antibodies cannot be used as a guide to select immunological probes for the detection of clinically relevant human auto-antibodies.
authors.affiliation: Laboratory of Peptide and Protein Chemistry and Biology, PeptLab, Via della Lastruccia 13, 50019, Sesto Fiorentino, Italy.|Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 13, 50019, Sesto Fiorentino, Italy.
authors.forename: Matthaia
authors.initials: M
authors.lastname: Ieronymaki
authors.affiliation: Laboratory of Peptide and Protein Chemistry and Biology, PeptLab, Via della Lastruccia 13, 50019, Sesto Fiorentino, Italy.|Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 13, 50019, Sesto Fiorentino, Italy.
authors.forename: Francesca
authors.identifier: 0000-0001-9908-5996
authors.initials: F
authors.lastname: Nuti
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", Via D. Montesano 49, 80131, Napoli, Italy.
authors.forename: Diego
authors.initials: D
authors.lastname: Brancaccio
authors.affiliation: Laboratory of Peptide and Protein Chemistry and Biology, PeptLab, Via della Lastruccia 13, 50019, Sesto Fiorentino, Italy.|Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmaceutical Sciences and Nutraceutics, University of Florence, Via Ugo Schiff 6, 50019, Sesto Fiorentino, Italy.
authors.forename: Giada
authors.initials: G
authors.lastname: Rossi
authors.affiliation: Laboratory of Peptide and Protein Chemistry and Biology, PeptLab, Via della Lastruccia 13, 50019, Sesto Fiorentino, Italy.|Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmaceutical Sciences and Nutraceutics, University of Florence, Via Ugo Schiff 6, 50019, Sesto Fiorentino, Italy.
authors.forename: Feliciana
authors.identifier: 0000-0001-5747-2285
authors.initials: F
authors.lastname: Real-Fernández
authors.affiliation: PeptLab, UCP Platform and Laboratory of Chemical Biology EA4505, University of Cergy-Pontoise, 5 mail Gay-Lussac, 95031, Cergy-Pontoise Cedex, France.
authors.forename: Yihong
authors.initials: Y
authors.lastname: Cao
authors.affiliation: PeptLab, UCP Platform and Laboratory of Chemical Biology EA4505, University of Cergy-Pontoise, 5 mail Gay-Lussac, 95031, Cergy-Pontoise Cedex, France.
authors.forename: Olivier
authors.initials: O
authors.lastname: Monasson
authors.affiliation: PeptLab, UCP Platform and Laboratory of Chemical Biology EA4505, University of Cergy-Pontoise, 5 mail Gay-Lussac, 95031, Cergy-Pontoise Cedex, France.
authors.forename: Maud
authors.initials: M
authors.lastname: Larregola
authors.affiliation: PeptLab, UCP Platform and Laboratory of Chemical Biology EA4505, University of Cergy-Pontoise, 5 mail Gay-Lussac, 95031, Cergy-Pontoise Cedex, France.
authors.forename: Elisa
authors.initials: E
authors.lastname: Peroni
authors.affiliation: PeptLab, UCP Platform and Laboratory of Chemical Biology EA4505, University of Cergy-Pontoise, 5 mail Gay-Lussac, 95031, Cergy-Pontoise Cedex, France.
authors.forename: Jacques
authors.initials: J
authors.lastname: Uziel
authors.affiliation: Laboratory of Peptide and Protein Chemistry and Biology, PeptLab, Via della Lastruccia 13, 50019, Sesto Fiorentino, Italy.|Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 13, 50019, Sesto Fiorentino, Italy.
authors.forename: Giuseppina
authors.initials: G
authors.lastname: Sabatino
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", Via D. Montesano 49, 80131, Napoli, Italy.
authors.forename: Ettore
authors.identifier: 0000-0003-4324-7997
authors.initials: E
authors.lastname: Novellino
authors.affiliation: Department of Pharmacy, University of Naples "Federico II", Via D. Montesano 49, 80131, Napoli, Italy.
authors.forename: Alfonso
authors.identifier: 0000-0001-7532-5449
authors.initials: A
authors.lastname: Carotenuto
authors.affiliation: Laboratory of Peptide and Protein Chemistry and Biology, PeptLab, Via della Lastruccia 13, 50019, Sesto Fiorentino, Italy.|Department of Chemistry "Ugo Schiff", University of Florence, Via della Lastruccia 13, 50019, Sesto Fiorentino, Italy.|PeptLab, UCP Platform and Laboratory of Chemical Biology EA4505, University of Cergy-Pontoise, 5 mail Gay-Lussac, 95031, Cergy-Pontoise Cedex, France.
authors.forename: Anna Maria
authors.identifier: 0000-0002-2947-7107
authors.initials: AM
authors.lastname: Papini
authors.affiliation: Laboratory of Peptide and Protein Chemistry and Biology, PeptLab, Via della Lastruccia 13, 50019, Sesto Fiorentino, Italy.|Department of Neurosciences, Psychology, Drug Research and Child Health, Section of Pharmaceutical Sciences and Nutraceutics, University of Florence, Via Ugo Schiff 6, 50019, Sesto Fiorentino, Italy.
authors.forename: Paolo
authors.identifier: 0000-0001-9577-5228
authors.initials: P
authors.lastname: Rovero
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000276:immunology; D000937:Antigen-Antibody Reactions; D018959:CD57 Antigens / Q000737:chemistry* / Q000276:immunology; D000939:Epitopes / Q000737:chemistry* / Q000276:immunology; D006801:Humans; D007694:Killer Cells, Natural / Q000737:chemistry* / Q000276:immunology; D051379:Mice; D009844:Oligosaccharides / Q000737:chemistry* / Q000276:immunology*; D010455:Peptides / Q000737:chemistry* / Q000276:immunology*; D011487:Protein Conformation; D013329:Structure-Activity Relationship; D020349:Surface Plasmon Resonance
chemical_list: D000911:Antibodies, Monoclonal; D018959:CD57 Antigens; D000939:Epitopes; D009844:Oligosaccharides; D010455:Peptides
keywords: antigens; biological activity; biosensors; structure-activity relationships; surface plasmon resonance