Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 16/10 Miklukho-Maklaya str., Moscow, 117997, Russia; National Medical Research Center for Obstetrics, Gynecology and Perinatology Named After Academician V.I. Kulakov of the Ministry of Healthcare of Russian Federation, 4 Oparina str., Moscow, 117997, Russia.
Shemyakin-Ovchinnikov Institute of Bioorganic Chemistry, 16/10 Miklukho-Maklaya str., Moscow, 117997, Russia; Auckland University of Technology, School of Engineering, Computer and Mathematical Sciences, Auckland, New Zealand.
Biochimie. 2022 Nov;202:94-102. doi: 10.1016/j.biochi.2022.08.009. Epub 2022 Aug 18.
Viscumin, a lectin used in anti-cancer therapy, was originally considered as βGal recognizing protein; later, an ability to bind 6'-sialyl N-acetyllactosamine (6'SLN) terminated gangliosides was found. Here we probed viscumin with a printed glycan array (PGA) containing a large number of mammalian sulfated glycans, and found a strong binding to glycans with 6-O-SuGal moiety as lactose, N-acetyllactosamine (LN), di-N-acetyllactosamine (LacdiNAc), and even 6-O-SuGalNAcα (but not SiaTn). Also, the ability to bind some of αGal terminated glycans, including Galα1-3Galβ1-4GlcNAc, was observed. Unexpectedly, only weak interaction was detected with parent neutral β-galactosides including LN-LN-LN and branched (LN)LN oligolactosamines; in the light of these data, one should not confidently classify viscumin as a β-galactoside-binding lectin. Carrying out PGA in the presence of neutral or sulfated/sialylated glycan, together with sequential elution from lactose-sepharose and consideration of the protein structure, lead to the conclusion that two glycan-binding sites of viscumin have different specificities, one of which prefers charged sulfated and sialylated moieties.
粘蛋白是一种用于癌症治疗的凝集素，最初被认为是识别βGal 的蛋白；后来，发现它能够结合 6'-唾液酰-N-乙酰乳糖胺（6'SLN）末端神经节苷脂。在这里，我们使用包含大量哺乳动物硫酸化糖的打印聚糖阵列（PGA）探测粘蛋白，并发现它与具有 6-O-SuGal 部分的糖强烈结合，如乳糖、N-乙酰乳糖胺（LN）、二-N-乙酰乳糖胺（LacdiNAc），甚至是 6-O-SuGalNAcα（但不是 SiaTn）。此外，还观察到它能够结合一些αGal 末端糖，包括 Galα1-3Galβ1-4GlcNAc。出乎意料的是，与包括 LN-LN-LN 和分支（LN）LN 寡乳糖胺在内的亲本中性 β-半乳糖苷的相互作用仅检测到较弱；根据这些数据，不应将粘蛋白自信地归类为β-半乳糖苷结合凝集素。在中性或硫酸化/唾液酸化糖存在下进行 PGA，以及从乳糖-琼脂糖的顺序洗脱，并考虑蛋白质结构，得出结论，粘蛋白的两个糖结合位点具有不同的特异性，其中一个优先结合带电的硫酸化和唾液酸化部分。
