Department of Chemistry, University of California, Berkeley, California 94720-1460, USA.
J Am Chem Soc. 2011 Oct 26;133(42):16970-6. doi: 10.1021/ja206324q. Epub 2011 Oct 3.
A new protein modification strategy has been developed that is based on an oxidative coupling reaction that targets electron-rich amino acids. This strategy relies on cerium(IV) ammonium nitrate (CAN) as an oxidation reagent and results in the coupling of tyrosine and tryptophan residues to phenylene diamine and anisidine derivatives. The methodology was first identified and characterized on peptides and small molecules, and was subsequently adapted for protein modification by determining appropriate buffer conditions. Using the optimized procedure, native and introduced solvent-accessible residues on proteins were selectively modified with polyethylene glycol (PEG) and small peptides. This unprecedented bioconjugation strategy targets these under-utilized amino acids with excellent chemoselectivity and affords good-to-high yields using low concentrations of the oxidant and coupling partners, short reaction times, and mild conditions.
一种新的蛋白质修饰策略已经被开发出来，该策略基于针对富电子氨基酸的氧化偶联反应。该策略依赖于四价铈（IV）硝酸铵（CAN）作为氧化试剂，并导致酪氨酸和色氨酸残基与苯二胺和茴香胺衍生物偶联。该方法首先在肽和小分子上进行了鉴定和表征，然后通过确定适当的缓冲条件来适应蛋白质修饰。使用优化的程序，使用聚乙二醇（PEG）和小肽选择性地修饰蛋白质上的天然和引入的可及溶剂残基。这种前所未有的生物偶联策略具有优异的化学选择性，针对这些未充分利用的氨基酸，使用低浓度的氧化剂和偶联剂、短反应时间和温和的条件，可以获得良好至高产率。
