Chandrasekaran E V, Xue Jun, Xia Jie, Khaja Siraj D, Piskorz Conrad F, Locke Robert D, Neelamegham Sriram, Matta Khushi L
Department of Cancer Biology, Roswell Park Cancer Institute, Buffalo, NY, 14263, USA.
Department of Chemical and Biological Engineering, State University of New York, Buffalo, NY, 14260, USA.
Glycoconj J. 2016 Oct;33(5):819-36. doi: 10.1007/s10719-016-9678-y. Epub 2016 Jun 18.
Plant lectins through their multivalent quaternary structures bind intrinsically flexible oligosaccharides. They recognize fine structural differences in carbohydrates and interact with different sequences in mucin core 2 or complex-type N-glycan chain and also in healthy and malignant tissues. They are used in characterizing cellular and extracellular glycoconjugates modified in pathological processes. We study here, the complex carbohydrate-lectin interactions by determining the effects of substituents in mucin core 2 tetrasaccharide Galβ1-4GlcNAcβ1-6(Galβ1-3)GalNAcα-O-R and fetuin glycopeptides on their binding to agarose-immobilized lectins PNA, RCA-I, SNA-I and WGA. Briefly, in mucin core 2 tetrasaccharide (i) structures modified by α2-3/6-Sialyl LacNAc, LewisX and α1-3-Galactosyl LacNAc resulted in regular binding to PNA whereas compounds with 6-sulfo LacNAc displayed no-binding; (ii) strucures bearing α2-6-sialyl 6-sulfo LacNAc, or 6-sialyl LacdiNAc carbohydrates displayed strong binding to SNA-I; (iii) structures with α2-3/6-sialyl, α1-3Gal LacNAc or LewisX were non-binder to RCA-I and compounds with 6-sulfo LacNAc only displayed weak binding; (iv) structures containing LewisX, 6-Sulfo LewisX, α2-3/6-sialyl LacNAc, α2-3/6-sialyl 6-sulfo LacNAc and GalNAc Lewis-a were non-binding to WGA, those with α1-2Fucosyl, α1-3-Galactosyl LacNAc, α2-3-sialyl T-hapten plus 3'/6'sulfo LacNAc displayed weak binding, and compounds with α2-3-sialyl T-hapten, α2.6-Sialyl LacdiNAc, α2-3-sialyl D-Fucβ1-3 GalNAc and Fucα-1-2 D-Fucβ-1-3GalNAc displaying regular binding and GalNAc LewisX and LacdiNAc plus D-Fuc β-1-3 GalNAcα resulting in tight binding. RCA-I binds Fetuin triantennary asialoglycopeptide 100 % after α-2-3 and 25 % after α-2-6 sialylation, 30 % after α-1-2 and 100 % after α-1-3 fucosylation, and 50 % after α-1-3 galactosylation. WGA binds 3-but not 6-Fucosyl chitobiose core. Thus, information on the influence of complex carbohydrate chain constituents on lectin binding is apparently essential for the potential application of lectins in glycoconjugate research.
植物凝集素通过其多价四级结构结合本质上具有柔性的寡糖。它们识别碳水化合物中的精细结构差异，并与粘蛋白核心2或复合型N-聚糖链以及健康组织和恶性组织中的不同序列相互作用。它们被用于表征在病理过程中修饰的细胞和细胞外糖缀合物。我们在此研究复杂的碳水化合物-凝集素相互作用，通过确定粘蛋白核心2四糖Galβ1-4GlcNAcβ1-6(Galβ1-3)GalNAcα-O-R和胎球蛋白糖肽中的取代基对它们与琼脂糖固定的凝集素PNA、RCA-I、SNA-I和WGA结合的影响。简而言之，在粘蛋白核心2四糖中：(i) 由α2-3/6-唾液酸化乳糖胺、LewisX和α1-3-半乳糖基乳糖胺修饰的结构导致与PNA有规律的结合，而含有6-磺基乳糖胺的化合物则不结合；(ii) 带有α2-6-唾液酸化6-磺基乳糖胺或6-唾液酸化乳糖二胺碳水化合物的结构与SNA-I有强烈结合；(iii) 具有α2-3/6-唾液酸化、α1-3半乳糖基乳糖胺或LewisX的结构不与RCA-I结合，仅含有6-磺基乳糖胺的化合物显示出弱结合；(iv) 含有LewisX、6-磺基LewisX、α2-3/6-唾液酸化乳糖胺、α2-3/6-唾液酸化6-磺基乳糖胺和GalNAc Lewis-a的结构不与WGA结合，具有α1-2岩藻糖基、α1-3-半乳糖基乳糖胺、α2-3-唾液酸化T-抗原加3'/6'磺基乳糖胺的化合物显示出弱结合，而含有α2-3-唾液酸化T-抗原、α2.6-唾液酸化乳糖二胺、α2-3-唾液酸化D-岩藻糖β1-3 GalNAc和岩藻糖α-1-2 D-岩藻糖β-1-3GalNAc的化合物显示出有规律的结合，GalNAc LewisX和乳糖二胺加D-岩藻糖β-1-3 GalNAcα导致紧密结合。RCA-I在α-2-3唾液酸化后100%结合胎球蛋白三触角去唾液酸糖肽，α-2-6唾液酸化后25%结合，α-1-2岩藻糖基化后30%结合，α-1-3岩藻糖基化后100%结合，α-1-3半乳糖基化后50%结合。WGA结合3-但不结合6-岩藻糖基壳二糖核心。因此，关于复杂碳水化合物链成分对凝集素结合影响的信息显然对于凝集素在糖缀合物研究中的潜在应用至关重要。
