基于哌啶的糖树枝状大分子作为蛋白质N-聚糖假体。
Piperidine-based glycodendrons as protein N-glycan prosthetics.
作者信息
Hudak Jason E, Belardi Brian, Appel Mason J, Solania Angelo, Robinson Peter V, Bertozzi Carolyn R
机构信息
Department of Chemistry, University of California Berkeley, CA 94720, USA.
Department of Chemistry, University of California Berkeley, CA 94720, USA; Department of Molecular and Cell Biology, University of California Berkeley, CA 94720, USA.
出版信息
Bioorg Med Chem. 2016 Oct 15;24(20):4791-4800. doi: 10.1016/j.bmc.2016.05.050. Epub 2016 May 25.
The generation of homogeneously glycosylated proteins is essential for defining glycoform-specific activity and improving protein-based therapeutics. We present a novel glycodendron prosthetic which can be site-selectively appended to recombinant proteins to create 'N-glycosylated' glycoprotein mimics. Using computational modeling, we designed the dendrimer scaffold and protein attachment point to resemble the native N-glycan architecture. Three piperidine-melamine glycodendrimers were synthesized via a chemoenzymatic route and attached to human growth hormone and the F region of human IgG. These products represent a new class of engineered biosimilars bearing novel glycodendrimer structures.
生成均匀糖基化的蛋白质对于定义糖型特异性活性和改进基于蛋白质的治疗方法至关重要。我们提出了一种新型糖树枝状假体，它可以位点选择性地连接到重组蛋白上，以创建“N-糖基化”糖蛋白模拟物。通过计算建模，我们设计了树枝状聚合物支架和蛋白质连接点，使其类似于天然N-聚糖结构。通过化学酶促路线合成了三种哌啶-三聚氰胺糖树枝状聚合物，并将其连接到人生长激素和人IgG的F区。这些产物代表了一类带有新型糖树枝状聚合物结构的新型工程生物类似物。
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