Research Of Selected Alkylation Of Histidine At N-? And N-? Sites And Its Fmoc Derivatives

The micro environment PH value of tumor cell is lower than that of normal cell,so it provide a target for the anti-tumor drugs development.Histidine can be protoned only in the acidic conditions,so the selected cell penetrating peptide(TH)showed a valuable acid depended penetrating activity to the tumor acidic mircro environment as a target.TH can be protoned to bring enough positive charge to show the penetrating activity when the pH is under 6.5.Histidine can be protoned because of its basic imidazole group nitrogen atom.The more increasing basicity of the imidazole ring,the more positive charge could be taken to increase the ability of the acidic relied penetrating activity in PH value from 5.7 to 7.2,when the electron donating group was introduced to the imizole group.In this research,the N-1 and N-3 sites of histidine were tried to be modified to increase the basicity.Then,we synthesised the Fmoc derivatives of the modified histidine to provide the materials for solid phase cell penetrating peptide synthesis.Synthetic routes of alkylation were compared and discussed to give a suitable preparation.The protected amino acids were synthesized for the synthesis and research of the acid activation CPPS.Reaction processes were inspected by T.L.C.Improved methods of extraction and separation were obtained.The structures of the products were confirmed by physical constants,MS and HNMR and the purities of the products were determined by HPLC.