Tn Antigen Mimics Based on sp2-Iminosugars with Affinity for an anti-MUC1 Antibody
Authors:
- Elena M. Sánchez FernándezEFElena M. Sánchez Fernández
- Claudio D. NavoCNClaudio D. Navo
- Rita Gonçalves-PereiraRGRita Gonçalves-Pereira
- Jesús H. BustoJBJesús H. Busto
- Gonçalo J. L. BernardesGBGonçalo J. L. Bernardes
- Gonzalo Jiménez-OsésGJGonzalo Jiménez-Osés
- Francisco CorzanaFCFrancisco Corzana
- José M. García FernándezJFJosé M. García Fernández
- Carmen Ortiz MelletCMCarmen Ortiz Mellet
- 25 July 2016
- journal article
- research article
- Published by American Chemical Society (ACS) in Organic Letters
- Vol. 18 (15) , 3890-3893
Abstract
The first examples of amino acid (Ser/Thr)–sp2-iminosugar glycomimetic conjugates featuring an α-O-linked pseudoanomeric linkage are reported. The key synthetic step involves the completely diastereoselective α-glycosylation of Ser/Thr due to strong stereoelectronic and conformational bias imposed by the bicyclic sp2-iminosugar scaffold. Mucin-related glycopeptides incorporating these motifs were recognized by the monoclonal antibody (mAb) scFv-SM3, with activities depending on both the hydroxylation pattern (Glc/Gal/GlcNAc/GalNAc) of the sp2-iminosugar and the peptide aglycone structure (Ser/Thr).Keywords
Funding Information
- Royal Society
- Medical Research Council
- Agencia de Innovación y Desarrollo de Andalucía (FQM2012-1467)
- Ministerio de Economía y Competitividad (CTQ2015-67727-R, CTQ2015-70524-R, RYC-2013-14706, SAF2013-44021-R, UNLR13-4E-1931)
- Directorate-General for Research and Innovation (333594)
- European Social Fund Plus
- European Regional Development Fund (CTQ2015-67727-R, CTQ2015-70524-R, RYC-2013-14706, SAF2013-44021-R, UNLR13-4E-1931)
This publication has 25 references indexed in Scilit:
- Recent Advance in Tumor-associated Carbohydrate Antigens (TACAs)-based Antitumor VaccinesACS Chemical Biology, 2016
- Glycosylation in cancer: mechanisms and clinical implicationsNature Reviews Cancer, 2015
- Deciphering the Non‐Equivalence of Serine and Threonine O‐Glycosylation Points: Implications for Molecular Recognition of the Tn Antigen by an anti‐MUC1 AntibodyAngewandte Chemie International Edition, 2015
- The Tn Antigen—Structural Simplicity and Biological ComplexityAngewandte Chemie International Edition, 2011
- Structure and Function of the Cell Surface (Tethered) MucinsAnnual Review of Physiology, 2008
- Serine versus Threonine Glycosylation: The Methyl Group Causes a Drastic Alteration on the Carbohydrate Orientation and on the Surrounding Water ShellJournal of the American Chemical Society, 2007
- Synthesis and Structural Model of an α(2,6)‐Sialyl‐T Glycosylated MUC1 Eicosapeptide under Physiological ConditionsChemistry – A European Journal, 2006
- Binding patterns of DTR-specific antibodies reveal a glycosylation-conditioned tumor-specific epitope of the epithelial mucin (MUC1)Glycobiology, 2004
- Conformational studies on the MUC1 tandem repeat glycopeptides: implication for the enzymatic O-glycosylation of the mucin protein coreGlycobiology, 2003
- Principles of Mucin Architecture: Structural Studies on Synthetic Glycopeptides Bearing Clustered Mono-, Di-, Tri-, and Hexasaccharide GlycodomainsJournal of the American Chemical Society, 2002