Research progress of synthetic methods of ［18F］F-DOPA / 中国药科大学学报

@#［18F］6-fluoro-3, 4-dihydroxy-L-phenylalanine(［18F］F-DOPA)has been used as a radiotracer for Parkinson′s disease over 30 years. The previously reported electrophilic synthesis method has low radiochemical yield(RCY), low specific activity(SA)and other defects. Recent reported nucleophilic synthesis of ［18F］F-DOPA could overcome the disadvantages. In this paper, the nucleophilic synthetic methods for ［18F］F-DOPA are reviewed.

Molecular dynamics simulation and analysis of BAFF which is incorporated with p-nitro-L-phenylalanine / 中国药科大学学报

In order to study the structure-function relationship in the protein which is incorporated with p-nitro-L-phenylalanine,the method of MD(Molecular Dynamics) simulation was established and successfully used in the analysis of protein which contains p-nitro-L-phenylalanine.The force field of CHARMM can only stimulate protein with natural amino acid in NAMD.Compared with phenylalanine,p-nitro-L-phenylalanine just has one more group of nitro.If the parameter of group of nitro was defined,the protein containing p-nitro-L-phenylalanine can be simulated.CGenFF-paramchem was used to calculate the energy and topological structure of p-nitro-L-phenylalanine' s new bonds (r),angles (θ),dihendrals (φ) and improper angle (ψ).And then the new defined parameter and topology information was input into the related parameter files and topology files in CHARMM.On the basis of correct parameter,NAMD can successfully simulate the modified BAFF(B lymphocyte stimulator) which contains p-nitro-L-phenylalanine.The changes in structure indicated that there might be new B cell epitopes.The temperature distribution of each frame in the process of dynamics stimulation was in accord with normal distribution,which proved the defined force field parameters was feasible.The RMSD of whole protein solution systemis 2.5.Calculate each resides' RMSF in BAFF,the RMSF of p-nitro-L-phenylalanine's residue is 3.7,which is obviously higher than that of the other residues in β-pleated sheet,and close to the loop rings,indicate that there might be variation in the area of p-nitro-L-phenylalanine residue and might produce new comformational epitopes.The results of MD stimulation will guide the immunogenicity experiments of p-nitro-L-phenylalanine modified proteins.

Synthesis and characterization of amphiphilic block copolymer of poly(L-phenylalanine)-b-poly(L-aspartic acid) / 国际药学研究杂志

Objective: To design and synthesize a different molecular mass block copolymer of poly(L-phenylalanine)-b-poly(L-aspartic acid)(PPA-PAA). Methods: The L-phenylalanine and L-aspartic acid were used as raw materials to synthesize L-phenylalanine N-carboxy-α-amino acid anhydride and L-aspartic acid-β-benzylester N-carboxy-α-amino acid anhydride. The target compounds of amphiphilic block copolymer of PPA-PAA were synthesized by ring-opening polymerization. The critical micelle concentration of the amphiphilic polymer was determined by pyrene fluorescence probe method. Results: The copolymers of hydrophobic chain segment 500, 2000, and 4000 were synthesized and the structures were confirmed by hydrogen nuclear magnetic resonance and Fourier transformed infrared. The critical micelle concentration of polymers changed with adjusting the feed ratio of PPA to PAA. Conclusion: The results show that the longer the hydrophobic chain segment of PPA is, the smaller the critical micelle concentration of polymers. The results lay the groundwork for further studying the stabilizing effect of the drug polymer nanoparticles with different properties.

Synthesis and characterization of amphiphilic block copolymer of poly (L-phenylalanine)-b-poly(L-aspartic acid) / 国际药学研究杂志

Objective To design and synthesize a different molecular mass block copolymer of poly(L-phenylalanine)-b-poly (L-aspartic acid)(PPA-PAA). Methods The L-phenylalanine and L-aspartic acid were used as raw materials to synthesize L-phenyl?alanine N-carboxy-ɑ-amino acid anhydride and L-aspartic acid-β-benzylester N-carboxy-ɑ-amino acid anhydride. The target com?pounds of amphiphilic block copolymer of PPA-PAA were synthesized by ring-opening polymerization. The critical micelle concentra?tion of the amphiphilic polymer was determined by pyrene fluorescence probe method. Results The copolymers of hydrophobic chain segment 500,2000,and 4000 were synthesized and the structures were confirmed by hydrogen nuclear magnetic resonance and Fouri?er transformed infrared. The critical micelle concentration of polymers changed with adjusting the feed ratio of PPA to PAA. Conclu?sion The results show that the longer the hydrophobic chain segment of PPA is,the smaller the critical micelle concentration of poly?mers. The results lay the groundwork for further studying the stabilizing effect of the drug polymer nanoparticles with different proper?ties.

Enhanced Accumulation of Scopoletin in Cell Suspension Culture of Spilanthes acmella Murr. Using Precursor Feeding

In this study, the various concentrations of casein hydrolysate (25, 50, 75, 100 mg/L) and L-phenylalanine (50, 100, 150, 200 µM/l) were incorporated in MS containing 15 µM BA plus 5 µM 2,4-D for enhancement of secondary metabolites in cell culture of Spilanthes acmella. The presence of casein hydrolysate in the nutrient medium improved the growth of cell biomass and the production of scopoletin. The addition of casein hydrolysate up to 75 mg/L stimulated the accumulation of scopoletin, but increasing excess 75 mg/L the level of casein hydrolysate reduced the production of scopoletin. The addition of L-phenylalanine in the nutrient medium was found to be more effective for production of secondary metabolite in S. acmella. The addition of 50 µM/L of L-phenylalanine in the medium increased scopoletin content to 27.12 ± 0.58 µg/g dry weight, compared to the scopoletin content of control at 7.89 ± 0.61 µg/g dry weight. The highest accumulation of scopoletin was observed in the 100 µM/L L-phenylalanine in cell suspension, which was 4.51 times more than the control. As a result, using moderate concentration of L-phenylalanine was ideal for the production of scopoletin. In general, casein hydrolysate was more effective than L-phenylalanine for production of scopoletin and growth of cell biomass in the cell culture of S. acmella.

Design, synthesis and evaluation of new L-phenylalanine derivatives as acetylcholinesterase inhibitors / 中国药学杂志

OBJECTIVE: To research the effect of new L-phenylalanine derivatives on acetylcholinesterase (AChE) activity. METHODS: New L-phenylalanine derivatives were synthesized from substituted 2-bromo-l-acetophenones by four steps reaction, and their inhibitory activities on AChE were measured by Ellman method in vitro. RESULTS: The evaluation results showed that most derivatives possessed AChE inhibitory effect and the activity of compound 8b was the most potent with an IC50 value of 8.73 × 10-6 mol · L-1, which was more potent than that of rivastigmine; moreover, compound 8b had no inhibitory activities to BuChE. CONCLUSION: The inhibitory activities of new L-phenylalanine derivatives on acetylcholinesterase are worth studying further.

Validação intralaboratorial de metodologia quantitativa para determinação de L-fenilalanina em farinha de trigo por espectrofotometria derivada segunda / Single-laboratory validation of a quantitative methodology for determination of L-phenylalanine in wheat flour by second derivative spectrophotometry

O objetivo deste trabalho foi validar um método quantitativo para determinação de L-fenilalanina (Fen) em farinha de trigo por espectrofotometria derivada segunda. A amostra de farinha de trigo, na quantidade de 0,525g, foi submetida à hidrólise ácida com HCl a 5,7 mol/L, a 110 °C, por 24 h. O material hidrolisado foi reconstituído para 50 mL com tampão fosfato de sódio a 0,1 mol/L, pH 7,0. As soluções preparadas a partir dessa amostra foram submetidas às leituras de absorvância, entre 230 nm e 280 nm, em espectrofotômetro UV/VIS. Os espectros de derivada segunda foram traçados e os valores das áreas dos picos negativos foram utilizados para estimar os teores de Fen. A linearidade do método foi demonstrada na faixa de 0,010 mg/mL a 0,035 mg/mL (correspondente a teores de 251 mg/100g a 877 mg/100g de Fen em farinha de trigo). Efeitos de matriz foram observados. A determinação de Fen não sofreu interferência de compostos como L-tirosinae L-triptofano. As porcentagens de recuperação variaram de 81% a 118% e os desvios padrão relativos de repetitividade e reprodutibilidade parcial foram respectivamente 11% e 15%, para amostras contendo 354 mg/100g, demonstrando adequada recuperação e precisão do método. Os limites de detecção e quantificação foram, respectivamente, 63 mg/100ge 175 mg/100g. Os parâmetros de desempenho estudados indicaram adequação do método para o monitoramento e controle de teores de Fen em farinha de trigo.

Product stabilization of the two forms of carboxypeptidase A from buffalo pancreas.

The two forms of buffalo carboxypeptidase A lose a part of their activity when incubated at their optimal temperature. Both the forms are protected from heat denaturation by L-phenylalanine, one of the reaction products while the other reaction product hippuric acid provides only limited protection. It has also been shown that L-phenylalanine and hippuric acid bind at the same site of the enzyme and that the release of L-phenylalanine follows that of hippuric acid. On this basis, a new mechanism for the hydrolysis of acyldipeptides by carboxypeptidase A has been proposed.