Synthesis and Theoretical Studies of Phosphoryl Amino Acid Analogue

Phosphoryl amino acids and their analogues are continuing to be increasingly important as potential enzyme inhibitors, mechanistic probes for proteases^[1,2]. Previously, a series of investigations on the structure-reactivity relationship about phosphoryl amino acids 1 had been carried out, the results showed that the co-participation of phosphoryl group, carboxyl group and residues of amino acids were essential and their biomimic reaction mechanisms were commonly through a penta-coordinate intramolecular mixed carboxylic-phosphoric anhydride intermediates^[3].     

Analysis of the phosphoryl transfer mechanism of c-AMP dependent protein kinase (PKA) by penta-coodinate phosphoric transition state theory

This review briefly covers recent literature of research on the phosphoryl transfer mechanism of PKA. Combining experimental and theoretical calculation results on enzymes with experimentally observed biomimic activities of phosphoryl amino acids and a small molecular model of catalytic core in PKA, a novel mechanism was proposed. The cooperative participation roles of both Asp166 and Lys168 via a penta-coodinate phosphoric intermediate was elucidated to conciliate the current different views of the phosphoryl transfer mechanism of PKA. Since many ATP-binding enzymes may share a similar phosphoryl transfer mechanism, this proposed mechanism might also apply to the mechanism of these enzymes, e.g., molecular motor and phosphatase among others.     

Activity difference between alpha-COOH and beta-COOH in N-phosphorylaspartic acids

N-phosphorylamino acids are chemically active species that have many biomimic activities. alpha-COOH in amino acids and peptides behaviors rather differently than beta-COOH in many biochemical processes and takes a more important role in the origin of life. Activity differences between alpha-COOH and beta-COOH in the peptide formation of phosphoryl amino acids are studied by 1D, 2D NMR techniques and by ab initio and density functional theory (DFT) calculations in this paper. Phosphoryl dipeptide is formed directly from phosphoryl aspartic acids without any coupling reagents. Only the alpha-dipeptide ester is observed by 1D (1)H, (13)C, and (31)P NMR and 2D NMR. In the ab initio and DFT calculations, the pentacoordinate phosphorane intermediates containing five-membered rings are predicted to be more favored than those with six-membered rings. Both the experimental results and the theoretical calculations suggest that only the alpha-COOH group is activated by N-phosphorylation in N-phosphorylaspartic acid under mild conditions.     

Differentiation of α‐COOH from β‐COOH in aspartic acids by N‐phosphorylation

The biomimic reactions of N‐phosphoryl amino acids, which involved intramolecular penta‐coordinate phosphoric‐carboxylic mixed anhydrides, are very important in the study of many biochemical processes. The reactivity difference between the α‐COOH group and β‐COOH in phosphoryl amino acids was studied by experiments and theoretical calculations. It was found that the α‐COOH group, and not β‐COOH, was involved in the ester exchange on phosphorus in experiment. From MNDO calculations, the energy of the penta‐coordinate phosphoric intermediate containing five‐member ring from α‐COOH was 35 kJ/mol lower than that of the six‐member one from β‐COOH. This result was in agreement with that predicted by HF/6‐31G** and B3LYP/6‐31G** calculations. Theoretical three‐dimensional potential energy surface for the intermediates predicted that the transition states 4 and 5 involving α‐COOH or β‐COOH group had energy barriers of ΔE=175.8 kJ?mol^?1 and 210.4 kJ?mol^?1, respectively. So the α‐COOH could be differentiated from β‐COOH intramolecularly in aspartic acids by N‐phosphorylation. © 2001 John Wiley & Sons, Inc. Int J Quant Chem 83: 41–51, 2001     

Interaction between N-Phospho-Amino Acids and Nucleoside in Aqueous Medium

Thebiosynthesisofnucleicacid,oneofthemostimportantbio-macromolecules,isahighlyelegantprocess,whichinvolvestheparticipationofmanyenzymesandenergycarriers,suchasATP',whilechemicalsynthesisofoligonucleotidesgenerallyinvolvescomplicatedprotectinganddeprotectingprocesses'.Inthepreviouswork,nucleotidesandoligonucleotidesweredirectlyformedacthereaction,,-ofN-(O,O-diisopropyl)phosphorylthreonineanduridineinanhydrouspyridine'.SoN-(O,O-diisopropyl)phospho-aminoacid(DIPP-aa)wasproposedasamodelcompou…     

N-磷酰化氨基酸与核糖核苷反应的研究

研究了Ｎ－磷酰化氨基酸与核苷在水溶液中的反应，反应中能够同时生成小肽和小的寡核苷酸；不同的Ｎ－磷酰化氨基酸与不同的核苷之间的反应具有一定的选择性。     

ESI／MS of N-（O, O-Diisopropyl） Phosphoryl Aromatic Amino Acids and their Stability Investigation Using HPLC／UV／ESI／MS

The full scan ESI/MS and ESI/MS^2 of N-(O, O-diisopropyl) phosphoryl aromatic amino acids (DIPPAAAs), N-(O, O-diisopropyl) phosphoryl phenylalanine, N-(O, O-diisopropyl)phosphoryl tryptophan and N-(O, O-diisopropyl) phosphoryl tyrosine, were obtained. The specific ions for them were found. Their stability in the LC mobile phase was investigated using developed HPLC/UV/ESI/MS and the results demonstrated that the DIPPAAAs were stable in the mobile phase (5 mmol/L NH4Ac-MeCN (80:20,v/v, pH7.5) within 48 h.     

Elucidation of O-Phosphoryl and N-Phosphoryl Amino Acids by Electrospray Ionization Tandem Mass Spectrometry

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). Besides 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.     

Electrochemical Acetylcholine Chloride Biosensor Using an Acetylcholine Esterase Biomimic

Abstract

Pure enzymes are costly and highly sensitive to change in pH, temperature, ionic strength etc. Hence biomimetic or synthetic enzymes could be useful alternatives to such natural proteins. Although the selectivity of a biomimic is somewhat less than that of enzyme, it can be used as a detector element in inexpensive but stable biosensors. An organic compound, 4-[(1E)-ethanehydrazonoyl]benzoic acid, has been designed and synthesized as biomimic for the enzyme acetylcholine esterase. An acetylcholine chloride two-electrode screen-printed sensor was first developed using the immobilized enzyme acetylcholine esterase. The performance of the mimic in the hydrolysis of acetylcholine chloride was then tested with the same transducer by immobilizing the biomimic in place of the enzyme. The response of the sensor constructed using the mimic was comparable to that of the pure acetylcholine esterase enzyme electrode.     

Convenient synthesis of some optically active 1,4-benzodiazepin-2,5-diones

Isatoic anhydride was reacted with several L-amino acids to give the corresponding （2S）-N-（o-aminobenzoyl）-2-alkylaminoacetic acids. The latter compounds were treated with phosphoryl chloride under reflux temperature to afford the cyclized products, （3S）-3-alkyl-3,4-dihydro- 1 H- 1,4-benzodiazepin-2,5-diones. 2007 M. Bakavoli. Published by Elsevier B.V. on behalf of Chinese Chemical Society. All rights reserved.     

Stereospecific halogenation of ethyl methyl phosphorothioic acid

Tetramethyl-α-halogenoenamines are useful reagents for the stereospecific conversion of phosphorothioic acids to the corresponding phosphoryl halides.     

Nucleophilic Fluorination of α‐Aroylphosphinates with Morpholinosulfur Trifluoride

Nucleophilic fluorination of aroyl‐phenyl‐phosphinates is highly dependent on the nature of the alkoxy substituents attached to the phosphoryl group. A reaction of aroyl‐phenyl‐phosphinates with morpholinosulfur trifluoride was shown to be a convenient synthetic method for high‐yield synthesis of α,α‐difluorobenzyl‐phenyl‐phosphinates using steric protection of the phosphoryl group by a bulky isopropoxy substituent. The methyl esters of aroylphosphinic acids in the same reaction conditions yield (fluoro‐diaryl‐methyl)‐pentafluorophosphates as the main reaction products.     

六配位磷化学和生命化学

氨基酸侧链作为调节N-磷酸基氨基酸的化学反应性时供给设备而起作用, 这一调节作用是通过磷酰基的参与而实现。     

Synthesis and Extractive Properties of Hexaphosphorylated Calix[6]arenes

A series of calix[6]arenes substituted with phosphoryl functional groups were prepared by the Arbuzov reaction of hexakis(chloromethyl)calix[6]arene hexamethyl ether with isopropyl esters of trivalent phosphorus acids, followed by appropriate chemical transformations. Molecular modeling and NMR data show that phosphorylated calix[6]arenes exist in the stereochemically labile 1,2-alternate conformation. The extractive power of these compounds with respect to americium and europium was studied. Due to the cooperative binding of the metal cation with phosphoryl groups, the phosphorylated calixarenes are more effective extractants than their acylcic analogs and commercial organophosphorus extractants.     

Synthesis and Crystal Structure of Dipotassium Salts of N-Alkyl-N-{[O-alkoxy(hydroxy)phosphoryl]methyl}ditiocarbamic Acids

Russian Journal of General Chemistry - A one-pot method for the synthesis of dipotassium salts of N-alkyl-N-{[O-alkoxy(hydroxy)phosphoryl]methyl}dithiocarbamic acids has been elaborated....     

N-Phospho-α-Amino Acids and Co-Evolution of Nucleic Acid and Protein

N-phospho-α -amino acids obtainable from aqueous condition were different from their corresponding β -analogues intrinsically. As the self-reproduction unites, N-phospho-α -amino acids were capable to produce non-random oligopeptides. As the phosphoryl donor, they were able to phosphorylate the nucleosides much faster than the deoxynucleosides.     

磷酰氨基酸的酯交换反应研究

本文利用^3^1P NMR , 对比研究了磷酰化组氨酸与其它磷酰化氨基酸和一级醇的磷上酯交换的反应速度,实验表明磷酰化组氨酸的反应速度最快. 由此提出了以下机理:由于咪唑环的参与,磷可以形成六配位过渡态,从而加快了反应速度.     

Hexa-Coordinate phosphorus Chemistry and Life Chemistry

The amino acids' side chains were acting as the relay device to regulate the chemical reactivi-ties of the N-phosphoryl amino acids. These modulation effects were performed through the partici-pation of the phosphoryl group.     

Identification of self-assembly products from N-phosphoamino acids by electrospray ionization mass spectrometry

The self-assembly products of N-(O,O'-diisopropyl)-L-alpha-amino acids in aqueous media, N-(O,O'-diisopropyl)phosphoryl dipeptides and tripeptides, were identified by electrospray ionization mass spectrometry. A stepwise fragmentation of the [M + H](+) ions from the C-terminus of N-phosphopeptides was observed. Copyright 2000 John Wiley & Sons, Ltd.     

五氯化磷辅助下氨基酸的自组装成肽反应研究

L-α-氨基酸和D-α-氨基酸可与五氯化磷直接发生磷酰化反应，随后自组装成多肽，但β-氨基酸不能成肽，DL-α-氨基酸成肽困难；在SOCl2存在下，α-氨基酸也不能成肽，用电喷雾质谱研究了氨基酸的自组装反应，反应过程中有五元环状的氨基酸五配位磷中间体生成，使用硅烷基保护的氨基酸，在^31PNMR中可观察到五配位磷中间体。