Ecole Polytechnique Fédérale de Lausanne (EPFL), Institut des Matériaux and Institut des Sciences et Ingénierie Chimiques, Lausanne, Switzerland.
Biomacromolecules. 2011 Feb 14;12(2):482-93. doi: 10.1021/bm101272g. Epub 2010 Dec 23.
In this study, the residue-selective modification of proteins with polymers at arginine residues is reported. The difficulty in modifying arginine residues lies in the fact that they are less reactive than lysine residues. Consequently, typical chemo-selective reactions which employ "kinetic" selectivity (active esters, Michael addition, etc.) cannot be used to target these residues. The chemistry exploited herein relies on "thermodynamic" selectivity to achieve selective modification of arginine residues. ω-Methoxy poly(ethylene glycol) bearing an α-oxo-aldehyde group was synthesized and used to demonstrate the selective modification of lysozyme at arginine residues. In addition, the optimization of reaction conditions for coupling as well as the stability of the formed adduct toward dilution, toward a nucleophilic buffer, and toward acidification are reported. It was concluded that this approach is a convenient, mild, selective, and catalyst-free method for protein modification.
本研究报告了在精氨酸残基上用聚合物对蛋白质进行残留选择性修饰的方法。修饰精氨酸残基的难点在于它们的反应活性不如赖氨酸残基。因此，通常采用“动力学”选择性的化学选择性反应（活性酯、迈克尔加成等）无法用于靶向这些残基。本文所利用的化学方法依赖于“热力学”选择性来实现精氨酸残基的选择性修饰。合成了带有α-氧代醛基的ω-甲氧基聚（乙二醇），并将其用于证明溶菌酶在精氨酸残基上的选择性修饰。此外，还报道了偶联反应条件的优化以及形成的加合物在稀释、亲核缓冲液和酸化条件下的稳定性。结论认为，该方法是一种方便、温和、选择性和无催化剂的蛋白质修饰方法。
