- Preparation method of N epsilon-tert-butoxycarbonyl-N alpha-fluorenylmethoxycarbonyl-N epsilon-methyl-lysine
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The invention discloses a preparation method of N epsilon-tert-butoxycarbonyl-N alpha-fluorenylmethoxycarbonyl-N epsilon-methyl-lysine. The preparation method comprises the following steps: taking N alpha-fluorenylmethoxycarbonyl-lysine hydrochloride as a raw material, performing alkylation with halide (R-X) under alkaline conditions, performing reductive amination on alkylate in an aqueous formaldehyde solution to introduce methyl, removing an R group of a reductive amination product under acidic conditions, then introducing a t-butyloxycarboryl (BOC) protecting group under alkaline conditions and performing re-crystallization treatment to obtain a product. The preparation method disclosed by the invention is simple in synthetic route and mild in reaction conditions, and the next-step reaction can be directly carried out after an intermediate is simply washed and concentrated. The reaction yield in each step is close to quantification, the total yield can reach above 80 percent, the purity of a final product exceeds 98 percent, and a safe and efficient synthetic route is provided for the preparation of the N epsilon-tert-butoxycarbonyl-N alpha-fluorenylmethoxycarbonyl-N epsilon-methyl-lysine.
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- 2,2′-Bipyridine and hydrazide containing peptides for cyclization and complex quaternary structural control
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A synthetic peptide containing two N?-methyl lysines (Ac-K(N?-Me)GYTGYTGK(N?-Me)D-OH) was alkylated with bipyridine (bipy) ligands substituted at the fifth (MP-5) and sixth (MP-6) positions, thereby creating Ac-K(N?-Me, N?-Bipy)GYTGYTGK(N?-Me, N?-Bipy)D-OH. Peptides with a bipyridine at the 6-position did not bind to Fe2+ and Zn2+. Peptides with a bipyridine at the 5-position bound these metals, and in the presence of one equivalent of a free bipy derivative folded into a macrocycle. Further, the free bipy derivative could also contain a cyclized peptide derived from hydrazone formation, resulting in a complex but controlled quaternary peptide structure.
- Hernandez, Erik T.,Escamilla, P. Rogelio,Kwon, Sang-Yop,Partridge, Jonathan,McVeigh, Matthew,Rivera, Sebastian,Reuther, James F.,Anslyn, Eric V.
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p. 8577 - 8582
(2018/06/11)
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- Analysis of JmjC Demethylase-Catalyzed Demethylation Using Geometrically-Constrained Lysine Analogues
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The dynamic post-translational modifications of histones play important roles in the regulation of transcription in animals. The demethylation of Nε-methyl lysine residues in the N-terminal tail of histone H3 is catalyzed by demethylases, of which the largest family is the ferrous iron and 2-oxoglutarate dependent demethylases (JmjC KDMs), which catalyze demethylation via initial hydroxylation of the N-methyl groups. We report studies on the conformational requirements of the JmjC KDM substrates using N-methylated lysine analogues prepared by metathesis reactions of suitably protected N-allylglycine. The results support the proposed requirement for a positively charged Nε-amino group in JmjC KDM catalysis. Demethylation of a trans-C-4/C-5 dehydrolysine substrate analogue was observed with representative KDM4 subfamily members KDM4A, KDM4B and KDM4E, and KDM7B, which are predicted, based on crystallographic analyses, to bind the Nε-methylated lysine residue in different conformations during catalysis. This information may be useful in the design of JmjC KDM selective inhibitors.
- Langley, Gareth W.,Brink?, Anne,Münzel, Martin,Walport, Louise J.,Schofield, Christopher J.,Hopkinson, Richard J.
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p. 755 - 762
(2016/04/05)
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- A convenient preparation of N ε-methyl-l-lysine derivatives and its application to the synthesis of histone tail peptides
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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.
- Chi, Hongfang,Islam, Md. Shahidul,Nsiama, Tienabe K.,Kato, Tamaki,Nishino, Norikazu
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p. 1305 - 1311
(2014/05/06)
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