Dept. Química Orgánica, Facultad de Química, Universidad de Sevilla , E-41012 Sevilla, Spain.
Dept. Química, Universidad de La Rioja, Centro de Investigación en Síntesis Química , E-26006 Logroño, Spain.
Org Lett. 2016 Aug 5;18(15):3890-3. doi: 10.1021/acs.orglett.6b01899. Epub 2016 Jul 25.
The first examples of amino acid (Ser/Thr)-sp(2)-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 sp(2)-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 sp(2)-iminosugar and the peptide aglycone structure (Ser/Thr).
报告了首例具有α-O-连接假端基键的氨基酸（Ser/Thr）-sp(2)-亚氨基糖糖 mimic 缀合物的实例。关键的合成步骤涉及由于双环 sp(2)-亚氨基糖骨架施加的强立体电子和构象偏差，导致 Ser/Thr 的完全非对映选择性α-糖苷化。含有这些基序的粘蛋白相关糖肽被单克隆抗体（mAb）scFv-SM3 识别，其活性取决于 sp(2)-亚氨基糖的羟化模式（Glc/Gal/GlcNAc/GalNAc）和肽糖苷配基结构（Ser/Thr）。
