The yield and purity of synthetic peptides were greatly related to the amino acid protection and activation during the synthesis process. Therefore, the amino acid protection and activation are the most important steps in peptide synthesis. By using tetrahydrofuran as the solvent, 9-fluorenylmethoxycarbonyl as protection group, 2-(7-azobenzotri- azol-1-yl)-N,N,N′,N′-tetramethyluronium hexafluorophosphate (HATU) as condensation reagent an amino protected histidine ester was given. In this article a novel synthesis method for N-(9- fluorenylmethoxycarbonyl)-histidine active ester was established. The reaction conditions for preparing this active ester were optimized. The experimental results indicated that solvents and active reagents had remarkable effects on the yield of active ester. The best conditions for preparing the active ester was a ratio of n (Fmoc-His-OH): n (HATU) = 1:1.2 with THF used as the solvent at room temperature. The yield of the final product was about 80% with a purity of over 85%. This simple method would provide fundamentals for the synthesis of other protected amino acid active esters.
Cite this paper
Y. Zhao, S. Zhang, S. Cui, H. Chen, B. Wang and S. Zhang, "A Novel Method for the Protection and Activation of Histidine," Advances in Materials Physics and Chemistry, Vol. 2 No. 4, 2012, pp. 226-228. doi: 10.4236/ampc.2012.24B057.
 S. B. Zhang, Y. N. Zhao, and B. D. Zhao. “Hybrids of nonviral vectors for gene delivery,” Bioconjugate Chem. vol. 21, pp. 1003-1009, June 2010.
 D. J. Coles, A. Esposito, and H. T. Chuah. “The synthesis and characterization of lipophilic peptide-based carriers for gene delivery,” Tetrahedron. vol. 66, pp.5435-5441, July 2010.
 Y. T. Ko, C. Falcao, and V. P. Torchilin. “Cationic liposomes loaded with proapoptotic peptide D-(KLAKLAK)2 and Bcl-2 antisense oligodeoxynucleotide G3139 for enhanced anticancer therapy,”Molecular Pharmaceutics, vol.6,pp.971-977, March 2009.
 D. L. McKenzie, K. Y. Kwok, and K. G. Rice. “A potent new class of reductively activated peptide gene delivery agents,” J. Biol. Chem., vol. 275, pp. 9970-9977, April 2000.
 M. A. Mintzer, E. E. Simanek. “Nonviral vectors for gene delivery,” Chem Rev., vol. 109, pp.259-302, April 2009.
 M. Nishikawa, M. Yamauchi, and K. Morimoto. “Heptocyte-targeted in vivo gene expression by intraveneous injection of plasmid DNA complexed with synthetic multi-functional gene delivery system,” Gene Ther.,vol. 7, pp.548-555, July 2000.
 M. J. Schuster, G. Y. Wu, and C. M.Walton. “Multicomponent DNA carrier with a vesicular stomatitis virus G-peptide greatly enhaances liver-targeted gene expression in mice,”Bioconjugate Chem.,vol.10, pp.1075-1083, October 1999.
 S. B. Zhang, Y. M. Xu, and B.Wang. “Cationic compounds used in lipoplexes and polyplexes for gene delivery,” J.Control Release, vol. 100, pp.165-180, November 2004.
 Y. N. Zhao,S. B. Zhang, and S. H. Cui. “Preparation of amino acid active ester in peptide intermediate,” Chemical Word, vol.2, pp. 105-109, February 2012.