1. A convenient preparation of N (ε)-methyl-L-lysine derivatives and its application to the synthesis of histone tail peptides
Hongfang Chi, Md Shahidul Islam, Tienabe K Nsiama, Tamaki Kato, Norikazu Nishino Amino Acids. 2014 May;46(5):1305-11. doi: 10.1007/s00726-014-1690-6. Epub 2014 Feb 23.
A convenient route is established for the preparation of N (α)-Fmoc-N (ε)-(Boc, methyl)-L-lysine and N (α)-Fmoc-N (ε)-dimethyl-L-lysine as building blocks to be used for the synthesis of methylated peptides. This methodology is based on the use of malonate derivatives and dibromobutane to produce key intermediates, L-2-amino-6-bromohexanoic acid derivatives, which could be modified to the required group at the ε-position. Fmoc-protection is accessible, so these compounds can be used in solution as well as in solid-phase peptide synthesis. Also the peptides containing these methylated lysines have been proved to resist the action of trypsin and lysyl endopeptidase. Thus, this new method could be considered as an improvement of the synthesis of N (ε)-methyl-L-lysine derivatives.
2. A genetically encoded photocaged Nepsilon-methyl-L-lysine
Yane-Shih Wang, Bo Wu, Zhiyong Wang, Ying Huang, Wei Wan, William K Russell, Pei-Jing Pai, Yin N Moe, David H Russell, Wenshe R Liu Mol Biosyst. 2010 Sep;6(9):1557-60. doi: 10.1039/c002155e. Epub 2010 Mar 30.
A photocaged N(epsilon)-methyl-L-lysine has been genetically incorporated into proteins at amber codon positions in Escherichia coli using an evolved pyrrolysyl-tRNA synthetase-pylT pair. Its genetic incorporation and following photolysis to recover N(epsilon)-methyl-L-lysine at physiological pH provide a convenient method for the biosynthesis of proteins with monomethylated lysines at specific sites.
3. Genetically encoding N(epsilon)-methyl-L-lysine in recombinant histones
Duy P Nguyen, Maria M Garcia Alai, Prashant B Kapadnis, Heinz Neumann, Jason W Chin J Am Chem Soc. 2009 Oct 14;131(40):14194-5. doi: 10.1021/ja906603s.
Lysine methylation is an important post-translational modification of histone proteins that defines epigenetic status and controls heterochromatin formation, X-chromosome inactivation, genome imprinting, DNA repair, and transcriptional regulation. Despite considerable efforts by chemical biologists to synthesize modified histones for use in deciphering the molecular role of methylation in these phenomena, no general method exists to synthesize proteins bearing quantitative site-specific methylation. Here we demonstrate a general method for the quantitative installation of N(epsilon)-methyl-L-lysine at defined positions in recombinant histones and demonstrate the use of this method for investigating the methylation dependent binding of HP1 to full length histone H3 monomethylated on K9 (H3K9me1). This strategy will find wide application in defining the molecular mechanisms by which histone methylation orchestrates cellular phenomena.
