蛋白质多肽类药物的脂肪酸修饰研究进展

Advances in Research on Modification of Protein and Peptide Drugs with Fatty Acids

随着基因工程技术的发展,蛋白质多肽药物的应用越来越受到人们的青睐。但此类药物具有血浆半衰期较短、免疫原性较强等不足之处,在很大程度上限制了其临床应用。因此,研究人员尝试采用各种化学方法对蛋白质多肽类药物加以修饰,以弥补这一不足。与PEG修饰、糖基化修饰、定点突变等方法相比,脂肪酸修饰除了可获得良好的生物活性、提高稳定性、降低免疫原性外,更重要的是由于脂肪酸是构成人体脂肪、类脂和细胞膜磷脂的重要成分,可有助于提高药物的脂溶性,增大肠道黏膜透过性,增强药物与受体的结合。对蛋白质多肽药物的脂肪酸修饰研究进展进行综述。

With the development of techniques in genetic engineering, protein and peptide drugs have gained increased popularity. However, their clinical application is limited by several shrotcomings such as short half-time and high imrnunogenicity, which leads to the recent efforts made by many researchers in various chemical modifications of protein and peptide drugs. Compared with PEG modification, glycosylation and site-directed mutagenesis, modification with fatty acids results in good biological activity, improved stability and reduced immunogenicity of protein and peptide drugs. What＇s more, as important components of body fat, lipids and cell membrane phospholipids, fatty acids can increase drug lipophilicity and permeability through intestinal mucosa, and promote the association of drugs with their receptors. In this article, current advances in research on the modification of protein and peptide drugs with fatty acids were reviewed.