Improving the therapeutic efficacy of peptides and proteins: A role for polysialic acids
Improving the therapeutic efficacy of peptides and proteins: A role for polysialic acids
复制标题
DOI：
10.1016/j.ijpharm.2005.06.007
复制
发表时间：
2005-08-26
影响因子：
5.8
通讯作者：
Laing, P
中科院分区：
文献类型：
--
作者：
Gregoriadis, G;Jain, S;Laing, P
肽和蛋白质药物是一类不断增长的治疗药物。然而，它们在临床上的有效应用受到一些问题的影响，例如循环血液中的蛋白水解、通过肾脏的过早清除以及免疫原性。许多方法已被用来规避这些缺点，包括改变初级肽结构、包埋到纳米粒子（例如脂质体）中以及与聚合物缀合。聚唾液酸化，即肽和蛋白质与天然存在的、可生物降解的 α-(2 -> 8) 连接的聚唾液酸的缀合，是最近的发展，它有望至少与聚乙二醇化一样有效，但没有潜在的毒性。一系列肽和蛋白质治疗剂的多唾液酸化导致蛋白水解显着减少，保留其体内活性，延长其循环半衰期并降低免疫原性和抗原性。预计多唾液酸化将产生具有显着改善的药理学特征的新一代肽和蛋白质构建体。 (c) 2005 Elsevier B.V. 保留所有权利。
Peptide and protein drugs are a growing class of therapeutics. However, their effective application in the clinic is compromised by problems, for instance proteolysis in the circulating blood, premature clearance through the kidneys, and immunogenicity. A number of approaches have been used to circumvent such shortcomings including changes in the primary peptide structure, entrapment into nanoparticles (e.g. liposomes) and conjugation to polymers. Polysialylation, namely, conjugation of peptides and proteins to the naturally occurring, biodegradable alpha-(2 -> 8) linked polysialic acid is a recent development, which promises to be at least as effective as PEGylation but without its potential toxicity. Polysialylation of a range of peptide and protein therapeutics has led to markedly reduced proteolysis, retention of their activity in vivo, prolongation of their half-life in the circulation and reduction in immunogenicity and antigenicity. It is anticipated that polysialylation will lead to a new generation of peptide and protein constructs with significantly improved pharmacological profiles. (c) 2005 Elsevier B.V. All rights reserved.