CNS active O-linked glycopeptides.

CNS active O-linked glycopeptides.
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DOI:
10.3389/fchem.2015.00040
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发表时间:
2015
影响因子:
5.5
通讯作者:
Polt R
Polt R
中科院分区:
化学3区
文献类型:
--
作者:
Jones EM;Polt R

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天然存在的糖肽和糖蛋白在生物过程中起着重要作用。糖基化是体内最常见的翻译后修饰之一。糖肽参与细胞信号传导和分选,为识别提供细胞表面标记。从药物设计和合成的角度来看,通过糖基化修饰肽可以提高糖肽在生命系统中的生物利用度和生物活性,而降解产物的毒性可以忽略不计。糖肽的合成可以通过在固相肽合成(SPPS)中加入糖基化的氨基酸来形成所需的肽,或者通过糖-氨基酸部分的结合来完成。此外,研究表明糖基化增加了多肽对血脑屏障(BBB)的渗透,这可能导致神经系统疾病的新疗法。最近糖肽的应用主要集中在外周给药后各种碳水化合物修饰的中枢活性肽对体内中枢神经系统(CNS)的影响。
Naturally occurring glycopeptides and glycoproteins play important roles in biological processes. Glycosylation is one of the most common post-translational modifications in vivo. Glycopeptides are involved in cell signaling and sorting, providing cell surface markers for recognition. From the drug design and synthesis perspective, modification of a peptide through glycosylation results in increased bioavailability and bioactivity of glycopeptides in living systems with negligible toxicity of degradation products. Glycopeptide synthesis can be accomplished through incorporation of a glycosylated amino acid in solid phase peptide synthesis (SPPS) to form the desired peptide, or via incorporation of sugar-amino acid moieties. Additionally, research indicates that glycosylation increases penetration of the blood-brain barrier (BBB) by peptides, which may lead to novel therapeutics for neurological disorders. Recent applications of glycopeptides have focused on the in vivo central nervous system (CNS) effects after peripheral administration of centrally active peptides modified with various carbohydrates.
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