RGD-xyloside conjugates prime glycosaminoglycans.
RGD-xyloside conjugates prime glycosaminoglycans.
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DOI：
10.1007/s10719-010-9306-1
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发表时间：
2010-08
影响因子：
3
通讯作者：
Kuberan, Balagurunathan
中科院分区：
文献类型：
--
作者：
Tran, Vy M.;Victor, Xylophone V.;Yockman, James W.;Kuberan, Balagurunathan
关键词：
糖胺聚糖 (GAG) 在各种心血管和癌症相关过程中发挥着决定性作用。 GAG 精细结构表达的变化归因于其生物合成和分解代谢酶的失调，是血管功能障碍和肿瘤进展的标志。 GAG 链在血液凝固、伤口愈合和肿瘤生物学中的广泛作用导致了修饰的 GAG 链、GAG 结合肽和基于 GAG 的酶抑制剂作为治疗剂的开发。木糖苷携带疏水性糖苷配基，已知可在各种系统中诱导 GAG 生物合成。鉴于GAG链在血管和肿瘤生物学中的重要作用，我们设想RGD缀合的木糖苷可以靶向活化的内皮细胞和癌细胞，已知这些细胞表达αvβ3整合素，从而调节病理过程。为了实现这一愿景，使用点击化学将木糖残基与含有线性和环状 RGD 的肽缀合。我们的结果表明，RGD 缀合的木糖苷能够在各种细胞类型中引发 GAG 链，未来的研究旨在评估此类木糖苷在治疗心肌梗塞以及癌症相关血栓并发症中的潜在效用。
Glycosaminoglycans (GAG) play decisive roles in various cardio-vascular & cancer-associated processes. Changes in the expression of GAG fine structures, attributed to deregulation of their biosynthetic and catabolic enzymes, are hallmarks of vascular dysfunction and tumor progression. Wide spread role of GAG chains in blood clotting, wound healing and tumor biology has led to the development of modified GAG chains, GAG binding peptides and GAG based enzyme inhibitors as therapeutic agents. Xylosides, carrying hydrophobic aglycone, are known to induce GAG biosynthesis in various systems. Given the important roles of GAG chains in vascular and tumor biology, we envision that RGD-conjugated xylosides could be targeted to activated endothelial and cancer cells, which are known to express αvβ3 integrin, and thereby, modulate the pathological processes. To accomplish this vision, xylose residue was conjugated to linear and cyclic RGD containing peptides using click chemistry. Our results demonstrate that RGD-conjugated xylosides are able to prime GAG chains in various cell types, and future studies are aimed toward evaluating potential utility of such xylosides in treating myocardial infarction as well as cancer-associated thrombotic complications.
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影响因子：
4.3
作者：
Kitagawa, H;Oyama, M;Sugahara, K
通讯作者：
Sugahara, K
DOI：
10.1073/pnas.82.10.3197
发表时间：
1985-01-01
影响因子：
11.1
作者：
ESKO, JD;STEWART, TE;TAYLOR, WH
通讯作者：
TAYLOR, WH
影响因子：
4.8
作者：
Kitagawa, H;Tone, Y;Sugahara, K
通讯作者：
Sugahara, K
影响因子：
4.6
作者：
Kaufmann, Doris;Fiedler, Anne;Weberskirch, Ralf
通讯作者：
Weberskirch, Ralf
影响因子：
3.2
作者：
Owen, Robert M.;Carlson, Coby B.;Kiessling, Laura L.
通讯作者：
Kiessling, Laura L.