A convenient preparation of N^sup [epsilon]^-methyl-l-lysine derivatives and its application to the synthesis of histone tail peptides

• Published in: Amino acids 2014-05, Vol.46 (5), p.1305
• Main Authors: Chi, Hongfang, Islam, Md Shahidul, Nsiama, Tienabe K, Kato, Tamaki, Nishino, Norikazu
• Format: Article
• Language: English
• ISSN: 0939-4451; 1438-2199
• DOI: 10.1007/s00726-014-1690-6

A convenient route is established for the preparation of N ^sup [alpha]^-Fmoc-N ^sup [straight epsilon]^-(Boc, methyl)-l-lysine and N ^sup [alpha]^-Fmoc-N ^sup [straight epsilon]^-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 [straight epsilon]-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 ^sup [straight epsilon]^-methyl-l-lysine derivatives.[PUBLICATION ABSTRACT]