A series of N-phosphoryl branched peptides were synthesized by coupling of various N-phosphoryl amino acids to L-Lysine methyl ester, and their structures were confirmed by 31P NMR, 1H NMR, MS and elemental analysis....A series of N-phosphoryl branched peptides were synthesized by coupling of various N-phosphoryl amino acids to L-Lysine methyl ester, and their structures were confirmed by 31P NMR, 1H NMR, MS and elemental analysis. The results of cell biological tests indicated that compound 1d and 1e obviously inhibited the growth of both K562 and A2780 cells.展开更多
The bio-mimic reactions of N-phosphoryl amino acids are very important in the study of many biochemical processes. The difference of reactivity between a-COOH and b-COOH in phosphoryl aspartic acid was studied by the...The bio-mimic reactions of N-phosphoryl amino acids are very important in the study of many biochemical processes. The difference of reactivity between a-COOH and b-COOH in phosphoryl aspartic acid was studied by theoretical study (Hartree-Fock and Density Functional methods) in this paper. The intermediates II containing five-membered ring were more stable than III with six-membered ring. While for intermediates III, the isomers with six-membered ring in apical-equatorial spanning arrangement were more stable than those with di-equatorial spanning arrangement. At B3LYP/6-31G** level, it was shown that transition states IV and V involving a-COOH or b-COOH group had energy barriers of DE = 58.67 kJmol-1 and 103.94 kJmol-1, respectively. These results were in agreement with the experimental data. So the a-COOH group was involved in form of the intramolecular penta-coordinate phosphoric-carboxylic mixed anhydride intermediates, but not b-COOH group.展开更多
The reactions of four different N-(O,O'-diisopropyl) phosphoamino acids (DIPP-aa), such as N-phosphoryl-L-α-alanine (DIPP- L-α-Ala), N-phosphoryl-D-α-alanine (DIPP-D-α-A1a), N-phosphoryl-β-alanine (DIPP...The reactions of four different N-(O,O'-diisopropyl) phosphoamino acids (DIPP-aa), such as N-phosphoryl-L-α-alanine (DIPP- L-α-Ala), N-phosphoryl-D-α-alanine (DIPP-D-α-A1a), N-phosphoryl-β-alanine (DIPP-β-A1a) and N-phosphoryl-γ-amino butyric acid (DIPP-γ-Aba), and four nucleosides, adenosine (A), guanosine (G), cytidine (C) and uridine (U), were studied by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and HPLC/ESI-MS. DIPP-L-α-A1a and DIPP-D-α-A1a produced the same phosphorylated nucleosides, dinucleotides and phosphoroligopeptide. However, DIPP-β-A1a and DIPP-γ-Aba gave no relevant products.展开更多
The β-carboxylic group plays an important role in the peptide formation,esterification and the ester exchange at the phosphoryl group of N-phosphorylated aspartic acid.
In the presence of histidine, N-(O,O-diisopropyl)phosphoryl serine could catalyze the cleavage of RNA in aqueous solution at neutral pH. The results were detected by sub-marine agarose gel electrophoresis and capillar...In the presence of histidine, N-(O,O-diisopropyl)phosphoryl serine could catalyze the cleavage of RNA in aqueous solution at neutral pH. The results were detected by sub-marine agarose gel electrophoresis and capillary zone electrophoresis. It was found that at high concentration histidine could cleave the RNA slightly. While the participation of DIPP-Ser could significantly accelerate the cleavage reaction. N-phosphodipeptide---N-(O,O-diisopropyl) Ser-His are proposed to be involved in the mechanism.展开更多
The peptide formation of N-phosphoryl aminoacids with amino acids proceeds in aqueous solution withoutany coupling reagents. After being separated in sephadex gelcolumn, the phosphoryl dipeptides were analyzed by thee...The peptide formation of N-phosphoryl aminoacids with amino acids proceeds in aqueous solution withoutany coupling reagents. After being separated in sephadex gelcolumn, the phosphoryl dipeptides were analyzed by theelectrospray ionization tandem mass spectrometry (ESIMS/MS). The result demonstrates that phosphoryl dipeptideswere datected in all the reaction systems. It is found tkat theformation of N-phosphoryl dipeptides is oriented: theN-terminal amino acid residues of the N-phosphoryl dipep-tides are from N-phosphoryl amino acids, and the peptideelongation happened at the C-terminal. Only adipeptide, noβ-dipeptide, is formed in the N-phosphoryl dipeptides,showing that α-carboxylic group is activated selectively byN-pbosphorylation. Theoretical calculation shows that thepeptide formation of N-phosphoryl amino acids might hap-pen through a pentu-coordinate carboxylic-phosphoric in-termediate in solution. These results might give some clues tothe stlidy on the origin of proteins and protein展开更多
The hydrolysis reactions of N-(O,O'diisopropyl)phosphoryl-L-α-alanine (DIPP-L-α-Ala), N-(O,O'diisopropyl)- phosphoryl-D-α-alanine (DIPP-D-α-Ala), N-(O,O'-diisopropyl)phosphoryl-β-alanine (DIPP-β-Al...The hydrolysis reactions of N-(O,O'diisopropyl)phosphoryl-L-α-alanine (DIPP-L-α-Ala), N-(O,O'diisopropyl)- phosphoryl-D-α-alanine (DIPP-D-α-Ala), N-(O,O'-diisopropyl)phosphoryl-β-alanine (DIPP-β-Ala) and N-(O,O'-diisopropyl)phosphoryl-γ-amino butyric acid (DIPP-γ-Aba), were studied by HPLC and their hydrolysis reaction kinetic equations were obtained. Under acid conditions, the reaction rate of DIPP-L-α-Ala was close to that of DIPP-D-α-Ala and the same rule was true between DIPP-β-Ala and DIPP-γ-Aba. Meantime, the reaction rate of DIPP-L/D-α-Ala was as 10 times as that of DIPP-β-Ala or DIPP-γ-Aba. Under basic conditions, the hydrolysis reactions of DIPP-β-Ala and DIPP-γ-Aba almost did not take place and the reaction rate of DIPP-L/D-α-Ala was about 1/10 of that under acid conditions. Moreover, theoretical calculation further illuminated the differences of the hydrolysis rate from the view of energy. The results would provide some helpful clues to why nature chose a-amino acids but not other kinds of analogs as protein backbones.展开更多
目的:观察电针对脑缺血大鼠前扣带皮质高迁移率族蛋白1(high mobility group protein 1,HMGB1)和磷酸化的c-Jun氨基酸末端激酶(phosphorylated c-Jun N-terminal kinase,p-JNK)的表达影响,探讨电针对脑缺血大鼠前扣带皮质的保护作用及...目的:观察电针对脑缺血大鼠前扣带皮质高迁移率族蛋白1(high mobility group protein 1,HMGB1)和磷酸化的c-Jun氨基酸末端激酶(phosphorylated c-Jun N-terminal kinase,p-JNK)的表达影响,探讨电针对脑缺血大鼠前扣带皮质的保护作用及机制。方法:将24只雄性SD大鼠随机分为假手术组、模型组、电针组和假电针组,6只/组。采用右侧大脑中动脉栓塞法制备脑缺血大鼠模型,电针组选取“百会”穴、左侧“足三里”穴进行电针刺激,1次/d,30 min/次,持续14 d;假电针组仅浅刺入两穴位皮下,接电针仪但不通电。采用Longa评分评估各组大鼠神经功能损伤情况;Nissl染色观察右侧前扣带皮质神经元的形态与分布情况;免疫组化检测右侧前扣带皮质HMGB1和p-JNK蛋白的表达情况。结果:与假手术组相比,模型组和假电针组大鼠神经功能缺损评分升高(P<0.01),右侧前扣带皮质区Nissl阳性神经元数量减少(P<0.01),HMGB1和p-JNK蛋白表达增加(P<0.01);与模型组相比,电针组大鼠在脑缺血第7天、14天时神经功能缺损评分降低(P<0.05),Nissl阳性神经元数量增加(P<0.01),HMGB1和p-JNK蛋白表达降低(P<0.01)。结论:电针可能通过抑制脑缺血后HMGB1和p-JNK的过表达,减轻前扣带皮质的损伤。展开更多
Mass spectroscopic characteristics of phosphoryl amino acids were studied in detail by positive and negative electrospray ionization mass spectrometry (ESI-MS) in conjunction with tandem mass spectrometry (MS/MS). Be...Mass spectroscopic characteristics of phosphoryl amino acids were studied in detail by positive and negative electrospray ionization mass spectrometry (ESI-MS) in conjunction with tandem mass spectrometry (MS/MS). Be- sides N-diisopropyloxyphosphoryl amino acids (N-DIPP-AA), O-phospho- and O-diisopropyloxyphosphoryl amino acids (O-DIPP-AA) were studied and compared to N-DIPP-AA. The fragmentation pathways of [M+H]+, [M+Na]+ and [M-H]- ions of phosphoryl amino acids were summarized. In addition to several similar patterns, each of them showed its characteristic fragmention.展开更多
The interactions of oxidative radicals (Br2?-, HO?etc.) with N-phosphoryl dipeptide derivatives (NDM-TrpOMe and NDT-MetOMe) have been investigated by using pulse radiolysis at different pH values. It has been found th...The interactions of oxidative radicals (Br2?-, HO?etc.) with N-phosphoryl dipeptide derivatives (NDM-TrpOMe and NDT-MetOMe) have been investigated by using pulse radiolysis at different pH values. It has been found that Br2?- and HO? radicals oxidize the Met-site and Trp-site in the dipeptide derivatives via formation of the three-electron-bonded intermediate and indolyl radical simultaneously. Then the intramolecular electron transfer along the peptide backbone occurs. The rate constants of electron transfer, k, have been determined and the reaction mechanism has been deduced.展开更多
Post-translational modification of proteins by N-phosphorylation of the basic amino acid residues plays important roles in biological processes. The high-energy P–N bond might have contributed to the evolution of pre...Post-translational modification of proteins by N-phosphorylation of the basic amino acid residues plays important roles in biological processes. The high-energy P–N bond might have contributed to the evolution of prebiotic chemistry. N-phosphoryl amino acids(PAAs) can serve as interesting small molecular models for the study of P–N bonds in prebiotic chemical evolution. PAAs are capable of simultaneously producing several important biomolecules such as polypeptides and oligonucleotides under mild reaction conditions. In this review, we describe the chemistry of PAAs, discusse their likely prebiotic origins and their reactivity and how they relate to biological P–N bond species. We also depict a possible prebiotic scenario mediated by PAAs in which PAAs may have acted as one of the essential forces driving prebiotic biomolecules to the first protocell.展开更多
基金This work is supported by Natural Science Foundation of Beijing City (7002006). Elemental analyses were performed by Institute of Chemistry Chinese Academy of Science.
文摘A series of N-phosphoryl branched peptides were synthesized by coupling of various N-phosphoryl amino acids to L-Lysine methyl ester, and their structures were confirmed by 31P NMR, 1H NMR, MS and elemental analysis. The results of cell biological tests indicated that compound 1d and 1e obviously inhibited the growth of both K562 and A2780 cells.
基金the National Natural Science Foundation of China (No. 29802006) the Teaching and Research Award Program for Outstanding Young Teachers in Higher Education Institutions of MOE P.R.C. and Tsinghua University.
文摘The bio-mimic reactions of N-phosphoryl amino acids are very important in the study of many biochemical processes. The difference of reactivity between a-COOH and b-COOH in phosphoryl aspartic acid was studied by theoretical study (Hartree-Fock and Density Functional methods) in this paper. The intermediates II containing five-membered ring were more stable than III with six-membered ring. While for intermediates III, the isomers with six-membered ring in apical-equatorial spanning arrangement were more stable than those with di-equatorial spanning arrangement. At B3LYP/6-31G** level, it was shown that transition states IV and V involving a-COOH or b-COOH group had energy barriers of DE = 58.67 kJmol-1 and 103.94 kJmol-1, respectively. These results were in agreement with the experimental data. So the a-COOH group was involved in form of the intramolecular penta-coordinate phosphoric-carboxylic mixed anhydride intermediates, but not b-COOH group.
基金The authors would like to thank the financial supports from the National Natural Science Foundation of China(No.20132020)the Ministry of Science and Technology.the Chinese Ministry of Education and Tsinghua University.
基金the National Natural Science Foundation of China(Nos.20572061,20672104)the Chinese Ministry of Education and Zhengzhou University for financial support.
文摘The reactions of four different N-(O,O'-diisopropyl) phosphoamino acids (DIPP-aa), such as N-phosphoryl-L-α-alanine (DIPP- L-α-Ala), N-phosphoryl-D-α-alanine (DIPP-D-α-A1a), N-phosphoryl-β-alanine (DIPP-β-A1a) and N-phosphoryl-γ-amino butyric acid (DIPP-γ-Aba), and four nucleosides, adenosine (A), guanosine (G), cytidine (C) and uridine (U), were studied by electrospray ionization tandem mass spectrometry (ESI-MS/MS) and HPLC/ESI-MS. DIPP-L-α-A1a and DIPP-D-α-A1a produced the same phosphorylated nucleosides, dinucleotides and phosphoroligopeptide. However, DIPP-β-A1a and DIPP-γ-Aba gave no relevant products.
文摘The β-carboxylic group plays an important role in the peptide formation,esterification and the ester exchange at the phosphoryl group of N-phosphorylated aspartic acid.
文摘In the presence of histidine, N-(O,O-diisopropyl)phosphoryl serine could catalyze the cleavage of RNA in aqueous solution at neutral pH. The results were detected by sub-marine agarose gel electrophoresis and capillary zone electrophoresis. It was found that at high concentration histidine could cleave the RNA slightly. While the participation of DIPP-Ser could significantly accelerate the cleavage reaction. N-phosphodipeptide---N-(O,O-diisopropyl) Ser-His are proposed to be involved in the mechanism.
基金the National Natural Science Foundation of China (Grant Nos. 20072023 and 20175026)the Teaching and Research Award Program for Outstanding Young Teachers in Higher Education Institute of Ministry of Education of China
文摘The peptide formation of N-phosphoryl aminoacids with amino acids proceeds in aqueous solution withoutany coupling reagents. After being separated in sephadex gelcolumn, the phosphoryl dipeptides were analyzed by theelectrospray ionization tandem mass spectrometry (ESIMS/MS). The result demonstrates that phosphoryl dipeptideswere datected in all the reaction systems. It is found tkat theformation of N-phosphoryl dipeptides is oriented: theN-terminal amino acid residues of the N-phosphoryl dipep-tides are from N-phosphoryl amino acids, and the peptideelongation happened at the C-terminal. Only adipeptide, noβ-dipeptide, is formed in the N-phosphoryl dipeptides,showing that α-carboxylic group is activated selectively byN-pbosphorylation. Theoretical calculation shows that thepeptide formation of N-phosphoryl amino acids might hap-pen through a pentu-coordinate carboxylic-phosphoric in-termediate in solution. These results might give some clues tothe stlidy on the origin of proteins and protein
基金Project supported by the National Natural Science Foundation of China (Nos. 20572061, 20672104).
文摘The hydrolysis reactions of N-(O,O'diisopropyl)phosphoryl-L-α-alanine (DIPP-L-α-Ala), N-(O,O'diisopropyl)- phosphoryl-D-α-alanine (DIPP-D-α-Ala), N-(O,O'-diisopropyl)phosphoryl-β-alanine (DIPP-β-Ala) and N-(O,O'-diisopropyl)phosphoryl-γ-amino butyric acid (DIPP-γ-Aba), were studied by HPLC and their hydrolysis reaction kinetic equations were obtained. Under acid conditions, the reaction rate of DIPP-L-α-Ala was close to that of DIPP-D-α-Ala and the same rule was true between DIPP-β-Ala and DIPP-γ-Aba. Meantime, the reaction rate of DIPP-L/D-α-Ala was as 10 times as that of DIPP-β-Ala or DIPP-γ-Aba. Under basic conditions, the hydrolysis reactions of DIPP-β-Ala and DIPP-γ-Aba almost did not take place and the reaction rate of DIPP-L/D-α-Ala was about 1/10 of that under acid conditions. Moreover, theoretical calculation further illuminated the differences of the hydrolysis rate from the view of energy. The results would provide some helpful clues to why nature chose a-amino acids but not other kinds of analogs as protein backbones.
文摘目的:观察电针对脑缺血大鼠前扣带皮质高迁移率族蛋白1(high mobility group protein 1,HMGB1)和磷酸化的c-Jun氨基酸末端激酶(phosphorylated c-Jun N-terminal kinase,p-JNK)的表达影响,探讨电针对脑缺血大鼠前扣带皮质的保护作用及机制。方法:将24只雄性SD大鼠随机分为假手术组、模型组、电针组和假电针组,6只/组。采用右侧大脑中动脉栓塞法制备脑缺血大鼠模型,电针组选取“百会”穴、左侧“足三里”穴进行电针刺激,1次/d,30 min/次,持续14 d;假电针组仅浅刺入两穴位皮下,接电针仪但不通电。采用Longa评分评估各组大鼠神经功能损伤情况;Nissl染色观察右侧前扣带皮质神经元的形态与分布情况;免疫组化检测右侧前扣带皮质HMGB1和p-JNK蛋白的表达情况。结果:与假手术组相比,模型组和假电针组大鼠神经功能缺损评分升高(P<0.01),右侧前扣带皮质区Nissl阳性神经元数量减少(P<0.01),HMGB1和p-JNK蛋白表达增加(P<0.01);与模型组相比,电针组大鼠在脑缺血第7天、14天时神经功能缺损评分降低(P<0.05),Nissl阳性神经元数量增加(P<0.01),HMGB1和p-JNK蛋白表达降低(P<0.01)。结论:电针可能通过抑制脑缺血后HMGB1和p-JNK的过表达,减轻前扣带皮质的损伤。
基金Project supported by the National Natural Science Foundation of China (No. 20175026).
文摘Mass spectroscopic characteristics of phosphoryl amino acids were studied in detail by positive and negative electrospray ionization mass spectrometry (ESI-MS) in conjunction with tandem mass spectrometry (MS/MS). Be- sides N-diisopropyloxyphosphoryl amino acids (N-DIPP-AA), O-phospho- and O-diisopropyloxyphosphoryl amino acids (O-DIPP-AA) were studied and compared to N-DIPP-AA. The fragmentation pathways of [M+H]+, [M+Na]+ and [M-H]- ions of phosphoryl amino acids were summarized. In addition to several similar patterns, each of them showed its characteristic fragmention.
基金Project supported by the National Natural Science Foundation of China (No. 39800036)the Youth Science Foundation of the University of Science and Technology of China.
文摘The interactions of oxidative radicals (Br2?-, HO?etc.) with N-phosphoryl dipeptide derivatives (NDM-TrpOMe and NDT-MetOMe) have been investigated by using pulse radiolysis at different pH values. It has been found that Br2?- and HO? radicals oxidize the Met-site and Trp-site in the dipeptide derivatives via formation of the three-electron-bonded intermediate and indolyl radical simultaneously. Then the intramolecular electron transfer along the peptide backbone occurs. The rate constants of electron transfer, k, have been determined and the reaction mechanism has been deduced.
基金supported by the National Basic Research Program of China(2013CB910700,2012CB821600)the National Natural Science Foundation of China(21232005,21375113,21305115)the Program of Chinese Ministry of Education for Changjiang Scholars and Innovative Research Team in University
文摘Post-translational modification of proteins by N-phosphorylation of the basic amino acid residues plays important roles in biological processes. The high-energy P–N bond might have contributed to the evolution of prebiotic chemistry. N-phosphoryl amino acids(PAAs) can serve as interesting small molecular models for the study of P–N bonds in prebiotic chemical evolution. PAAs are capable of simultaneously producing several important biomolecules such as polypeptides and oligonucleotides under mild reaction conditions. In this review, we describe the chemistry of PAAs, discusse their likely prebiotic origins and their reactivity and how they relate to biological P–N bond species. We also depict a possible prebiotic scenario mediated by PAAs in which PAAs may have acted as one of the essential forces driving prebiotic biomolecules to the first protocell.