Toward Bioinspired Galectin Mimetics: Identification of Ligand-Contacting Peptides by Proteolytic-Excision Mass Spectrometry.

Clinically relevant bioactivities of human galectins (adhesion/growth-regulatory galactoside-specific lectins) inspired the design of peptides as new tools to elicit favorable effects (e.g., in growth control) or block harmful binding (e.g., in tissue invasion). To obtain the bioinspired lead compou...

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Published in:Journal of the American Chemical Society Vol. 133; no. 38; pp. 14844 - 14848
Main Authors: Moise, Adrian, André, Sabine, Eggers, Frederike, Krzeminski, Mickael, Przybylski, Michael, Gabius, Hans-Joachim
Format: Article
Published: American Chemical Society 9/28/2011
Subjects:
Online Access:View this record in EBSCOhost
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      dt: 9/28/2011
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        10.1021/ja201967v
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        atl: Toward Bioinspired Galectin Mimetics: Identification of Ligand-Contacting Peptides by Proteolytic-Excision Mass Spectrometry.
      aug:
        au:
          Moise, Adrian
          André, Sabine
          Eggers, Frederike
          Krzeminski, Mickael
          Przybylski, Michael
          Gabius, Hans-Joachim
        affil:
          Department of Chemistry, University of Konstanz, 78464 Konstanz, Germany
          Institute of Physiological Chemistry, Faculty of Veterinary Medicine, Ludwig-Maximilians-Universität, 80539 München, Germany
          Department of NMR Spectroscopy, Bijvoet Center for Biomolecular Research, Utrecht University, 3584 CH Utrecht, The Netherlands
      su:
        GABA agonists
        Ligand binding (Biochemistry)
        Lead compounds
        Proteolytic enzymes
        Carbohydrates
        Glycoproteins
        Phylogeny
      sug:
        subj:
          GABA agonists
          Ligand binding (Biochemistry)
          Lead compounds
          Proteolytic enzymes
          Carbohydrates
          Glycoproteins
          Phylogeny
      ab: Clinically relevant bioactivities of human galectins (adhesion/growth-regulatory galactoside-specific lectins) inspired the design of peptides as new tools to elicit favorable effects (e.g., in growth control) or block harmful binding (e.g., in tissue invasion). To obtain the bioinspired lead compounds, we combined a proteolytic fragmentation approach without/with ligand contact (excision) with mass spectrometric identification of affinity-bound protein fragments, using galectin-1 and -3 as models. Two peptides from the carbohydrate recognition domains were obtained in each case in experimental series rigorously controlled for specificity, and the [157-162] peptide of galectin-3 proved to be active in blocking lectin binding to a neoglycoprotein and to tumor cell surfaces. This approach affords peptide sequences for structural optimization and intrafamily/phylogenetic galectin comparison at the binding-site level with a minimal requirement of protein quantity, and it is even amenable to mixtures.
      pubtype: Academic Journal
      doctype: Article
      src: R
    language: English
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