Transformation from block-type to graft-type oligonucleotide-glycopolymer conjugates by self-organization with half-sliding complementary oligonucleotides and their lectin recognition
Transformation from block-type to graft-type oligonucleotide-glycopolymer conjugates by self-organization with half-sliding complementary oligonucleotides and their lectin recognition
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DOI：
10.1021/bc0100152
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发表时间：
2001-09-01
影响因子：
4.7
通讯作者：
Kobayashi, K
中科院分区：
文献类型：
--
作者：
Akasaka, T;Matsuura, K;Kobayashi, K
通过将5 ' -巯基修饰的寡核苷酸与通过端粒化合成的碘乙酰胺化的糖共聚物偶联来制备带有α-甘露糖苷和β-半乳糖苷的嵌段型甘氨肽-糖共聚物缀合物。偶联物对双链体的DNA构象和解链行为的影响最小。它们通过与半滑动互补寡核苷酸杂交的自组织产生接枝型缀合物或以规则的间隔接枝有糖聚合物的大分子缺口DNA双链体，这使用尺寸排阻色谱和电泳证实。采用荧光法研究了嵌段型和自组织接枝型缀合物与凝集素的结合亲和力。具有甘露糖苷的接枝型双链组装体对Con A的亲和力比具有完全互补寡核苷酸的嵌段型单链或双链缀合物强约2倍。DNA-糖聚合物结合物的组装策略可能有助于构建新型糖簇，并为基因治疗提供新的方法。
Block-type oligonucleotide-glycopolymer conjugates bearing alpha -mannosides and beta -galactosides were prepared by coupling 5 ' -thiol-modified oligonucleotides with iodoacetamidated glycopolymers that were synthesized by telomerization. The conjugates minimally affected the DNA conformation and melting behavior of the duplex. Their self-organization via hybridization with the half-sliding complementary oligonucleotides produced graft-type conjugates or macromolecular gapped DNA duplexes grafted with glycopolymers at regular intervals, which was confirmed using size exclusion chromatography and electrophoresis. The binding affinity of block-type and self-organized graft-type conjugates to lectins was investigated using fluorometry. The affinity of the graft-type duplex assembly bearing mannosides to Con A was approximately 2 times stronger than that of block-type single-stranded or double-stranded conjugates with full complementary oligonucleotides. The organization strategy of DNA-glycopolymer conjugates might be useful for constructing novel glyco-clusters and also for developing a new methodology for gene therapy.