通过肟交换实现特定部位聚合物与CCL-5（调节激活正常T细胞表达和分泌因子）类似物的连接。

Site-specific polymer attachment to a CCL-5 (RANTES) analogue by oxime exchange.

作者信息

Shao Haiyan, Crnogorac Milan M, Kong Ting, Chen Shiah-Yun, Williams Jason M, Tack Janette M, Gueriguian Vincent, Cagle E Neil, Carnevali Maia, Tumelty David, Paliard Xavier, Miranda Les P, Bradburne James A, Kochendoerfer Gerd G

机构信息

Gryphon Therapeutics, 600 Gateway Boulevard, South San Francisco, CA 94080, USA.

出版信息

J Am Chem Soc. 2005 Feb 9;127(5):1350-1. doi: 10.1021/ja043096w.

DOI:10.1021/ja043096w

PMID:15686348

Abstract

A synthetic strategy that allows for the site-specific attachment of polymers such as poly(ethylene glycol) (PEG) to protein pharmaceuticals is described. PEG was attached to a 67-amino acid fully synthetic CCL-5 (RANTES) analogue at its GAG binding site both to reduce aggregation and to increase the circulating lifetime. Effective protection of an Aoaa chemoselective linker during peptide assembly, total chemical protein synthesis, and protein folding was achieved with an isopropylidene group. Mild deprotection of the resulting folded synthetic protein and subsequent polymer attachment occur without interference with the native folded structure and activity.

摘要

描述了一种合成策略，该策略允许将诸如聚乙二醇（PEG）等聚合物位点特异性地连接到蛋白质药物上。PEG被连接到一种67个氨基酸的全合成CCL-5（调节激活正常T细胞表达和分泌因子）类似物的糖胺聚糖结合位点，以减少聚集并延长循环寿命。通过亚异丙基有效地保护了肽组装、全化学蛋白质合成和蛋白质折叠过程中的Aoa化学选择性连接子。所得折叠合成蛋白的温和脱保护以及随后的聚合物连接在不干扰天然折叠结构和活性的情况下发生。