A STUDY ON THE "IN VITRO" SYNTHESIS OF CITRULLINE: PART I. EFFECT OF SOME N-ALKYL DERIVATIVES OF ASPARTIG ACID

1964 ◽  
Vol 42 (9) ◽  
pp. 1317-1324 ◽  
Author(s):  
Louis Berlinguet ◽  
René Charbonneau
Keyword(s):  
Aspartic Acid ◽  
Inhibitory Action ◽  
Liver Homogenate ◽  
Chelating Agent ◽  
Magnesium Ion ◽  
Carbamyl Phosphate ◽  
In Vitro Synthesis ◽  
Alkyl Derivatives ◽  
Derivatives Of

The effects of various N-alkyl derivatives of aspartic acid on the synthesis of citrulline in the presence of a particulate fraction obtained from a rat liver homogenate were studied. Even though aspartic acid has no role in this synthesis, both N-methyl and N-isopropyl aspartic acids were found to increase the synthesis of citrulline by 60%, whereas N-cyclohexyl aspartic acid decreased it by 50%. N-Allyl aspartic acid has the strongest effect which is an almost complete inhibition at low concentration of 1.2 × 10−2 M.It seems that N-allyl aspartic acid inhibits directly or indirectly the first step in the synthesis of citrulline leading to the formation of carbamyl phosphate. At various concentrations, none of the intermediates in this synthesis, except magnesium ion, can reverse the inhibition. In order that N-allyl aspartic acid retain its inhibitory action, the ω-carboxyl group has to be free and the double bond in the allyl group must be intact. From these results, it is postulated that N-allyl aspartic acid acts as a chelating agent for magnesium.

A STUDY ON THE "IN VITRO" SYNTHESIS OF CITRULLINE: PART II. EFFECT OF GLUTAMIC ACID AND DERIVATIVES IN THE PRESENCE OF FUMARIC ACID

1964 ◽  
Vol 42 (9) ◽  
pp. 1325-1330 ◽  
Author(s):  
René Charbonneau ◽  
Louis Berlinguet
Keyword(s):  
Glutamic Acid ◽  
Rat Liver ◽  
Fumaric Acid ◽  
Liver Homogenate ◽  
Particulate Fraction ◽  
In Vitro Synthesis ◽  
System L ◽  
Acyl Derivatives

The role of N-carbamyl, N-acetyl, and L-glutamic acids with and without fumaric acid on the "in vitro" synthesis of citrulline was studied by using a particulate fraction obtained from a rat liver homogenate and a partially purified citrulline-synthesizing enzyme system. In the presence of a particulate fraction of rat liver homogenate, N-carbamyl and N-acetyl-L-glutamic acids are unable to replace L-glutamic acid, which is essential for citrulline biosynthesis. However, in the presence of fumaric acid, they both give a better synthesis of citrulline than L-glutamic acid alone. It is postulated that the acyl derivatives serve only in the transport of "activated CO2" whereas fumaric acid enters the citric acid to furnish the essential ATP molecules. Glutamic acid would be able to perform both functions. However, in the presence of a system containing partially purified citrulline-synthesizing enzymes, L-glutamic acid is unable to replace N-carbamyl and N-acetyl-L-glutamic acids with or without fumaric acid. In such a system, L-glutamic acid cannot serve in the transport of "activated CO2". It is postulated that L-glutamic acid must be acetylated prior to its utilization in this respect.With the particulate fraction of rat liver homogenate, N-allyl aspartic acid inhibits totally the synthesis of citrulline both in the presence and absence of fumaric acid with or without glutamic or N-acetyl glutamic acids. It probably interferes with the transport of "activated CO2".

Synthesis and Cytostatic Activity of N-[2-(Phosphonomethoxy)alkyl] Derivatives of N6-Substituted Adenines, 2,6-Diaminopurines and Related Compounds

2001 ◽  
Vol 66 (10) ◽  
pp. 1545-1592 ◽  
Author(s):  
Antonín Holý ◽  
Ivan Votruba ◽  
Eva Tloušťová ◽  
Milena Masojídková
Keyword(s):  
Cytostatic Activity ◽  
Secondary Amines ◽  
Dimethylformamide Dimethylacetal ◽  
Alkyl Derivatives ◽  
Derivatives Of ◽  
Related Compounds ◽  
Substituted Adenines

N6-Substituted adenine and 2,6-diaminopurine derivatives of 9-[2-(phosphonomethoxy)- ethyl] (PME), 9-[(R)-2-(phosphonomethoxy)propyl] [(R)-PMP] and enantiomeric (S)-PMP series were synthesized by reactions of primary or secondary amines with 6-chloro-9-{[2-(diisopropoxyphosphoryl)methoxy]alkyl}purines (26-28) or 2-amino-6-chloro-9-{[2-(diisopropoxy- phosphoryl)methoxy]alkyl}purines (29-31) followed by treatment of the diester intermediates32with bromo(trimethyl)silane and hydrolysis. Diesters32were also obtained by reaction ofN6-substituted purines with synthons23-25bearing diisopropoxyphosphoryl group. Alkylation of 2-amino-6-chloropurine (9) with diethyl [2-(2-chloroethoxy)ethyl]phosphonate (148) gave the diester149which was analogously converted toN6-substituted 2,6-diamino- 9-[2-(2-phosphonoethoxy)ethyl]purines151-153. Alkylation ofN6-substituted 2,6-diaminopurines with (R)-[(trityloxy)methyl]oxirane (155) followed by reaction of thus-obtained intermediates156with dimethylformamide dimethylacetal and condensation with diisopropyl [(tosyloxy)methyl]phosphonate (158) followed by deprotection of the intermediates159gaveN6-substituted 2,6-diamino-9-[(S)-3-hydroxy-2-(phosphonomethoxy)propyl]purines160-163. The highest cytostatic activityin vitrowas exhibited by the followingN6-derivatives of 2,6-diamino-9-[2-(phosphonomethoxy)ethyl]purine (PMEDAP): 2,2,2-trifluoroethyl (53), allyl (54), [(2-dimethylamino)ethyl] (68), cyclopropyl (75) and dimethyl (91). In CCRF-CEM cells, the cyclopropyl derivative75is deaminated to the guanine derivative PMEG (3) which is then converted to its diphosphate.

Inhibition of urea cycle enzymes by aspartic acid analogues

1969 ◽  
Vol 47 (3) ◽  
pp. 361-369
Author(s):  
S. M. Bayer ◽  
W. C. McMurray
Keyword(s):  
Aspartic Acid ◽  
Energy Production ◽  
Urea Cycle ◽  
Argininosuccinate Synthetase ◽  
Substrate Type ◽  
Carbamyl Phosphate ◽  
Enzyme Preparations ◽  
Carbamyl Phosphate Synthetase ◽  
Liver Homogenates

The inhibition of urea biosynthesis by analogues of aspartic acid was studied in vitro in homogenates and enzyme preparations from rat liver. Each of the analogues tested inhibited the overall utilization of citrulline for urea formation by liver homogenates. The concentrations required to give 50% inhibition were: N-allylaspartate, 0.248 M; α-methylaspartate, 0.140 M; β-methylaspartate, 0.078 M; and β-hydroxy-β-methylaspartate, 0.038 M. The β-substituted analogues partly replaced aspartate as a substrate for citrulline utilization in liver homogenates. The replacement was probably due to transamination of the analogues with oxaloacetate, since the effect was not observed when the assay mixture did not contain a substrate which could yield oxaloacetate.A study of individual enzymes of the urea cycle showed that arginase, argininosuccinase, and ornithine transcarbamylase were not greatly affected by the analogues. However, carbamyl phosphate synthetase as well as argininosuccinate synthetase were strongly inhibited, suggesting that the analogues act by some mechanism other than simple antagonism of aspartate. Part of the inhibition was related to the ability of the analogues to complex Mg2+, since increased concentrations of Mg2+ prevented the inhibition of carbamyl phosphate synthetase and reduced the inhibition of argininosuccinate synthetase by α-methylaspartate and N-allylaspartate. In addition, β-methylaspartate was found to depress oxidative and phosphorylative reactions, thus interfering with the energy production required for urea formation.Aspartic acid in concentrations comparable with those required to effect inhibition by α-methylaspartate produced a marked inhibition of citrulline utilization in liver homogenates and of purified argininosuccinate synthetase. This observation suggests that part of the inhibitions observed with the analogues are of the "substrate type".

Synthesis of aspartic acid derivatives useful for the preparation of misacylated transfer RNAs

2000 ◽  
Vol 78 (6) ◽  
pp. 884-891 ◽  
Author(s):  
Michiel Lodder ◽  
Curtis F Crasto ◽  
Andrei L Laikhter ◽  
Haoyun An ◽  
Tuncer Arslan ◽  
...  
Keyword(s):  
Protein Synthesis ◽  
Amino Acid ◽  
Aspartic Acid ◽  
Side Chain ◽  
Transfer Rnas ◽  
Rna Ligase ◽  
T4 Rna Ligase ◽  
In Vitro Transcripts ◽  
Derivatives Of

Several derivatives of aspartic acid were protected on Nα as their NVOC derivatives, and on the side chain carboxylates as nitroveratryl esters. Following activation as the cyanomethyl esters, these fully protected aspartate derivatives were converted to the respective pdCpA esters. The protected aspartyl-pdCpA esters were then utilized as substrates for T4 RNA ligase in the presence of in vitro transcripts of tRNA lacking the pCpA dinucleotide normally found at the 3'-end. In this fashion, several misacylated tRNAs were prepared; following photolytic deprotection, these were employed successfully for incorporation into proteins at predetermined positions.Key words: aminoacylated nucleotides, amino acid protection, protein synthesis, tRNA activation.

scholarly journals In Vitro Antiherpesviral Activity of 5-Alkyl Derivatives of 1- -D-Arabinofuranosyluracil

1979 ◽  
Vol 16 (2) ◽  
pp. 158-163 ◽  
Author(s):  
H. Machida ◽  
S. Sakata ◽  
A. Kuninaka ◽  
H. Yoshino ◽  
C. Nakayama ◽  
...  
Keyword(s):  
Alkyl Derivatives ◽  
Derivatives Of

Small 9-Alkyl Derivatives of 10-Hydroxycamptothecin with Potent Antitumor Activity in Vitro and in Vivo

2005 ◽  
Vol 0 (0) ◽  
pp. 0-0
Author(s):  
H. Gao ◽  
M. Huang ◽  
J. Sun ◽  
H. Shen ◽  
W. Lu ◽  
...  
Keyword(s):  
Antitumor Activity ◽  
Alkyl Derivatives ◽  
Derivatives Of

scholarly journals Molecular Characterization of a Thermostable Cyanophycin Synthetase from the Thermophilic Cyanobacterium Synechococcus sp. Strain MA19 and In Vitro Synthesis of Cyanophycin and Related Polyamides

2002 ◽  
Vol 68 (1) ◽  
pp. 93-101 ◽  
Author(s):  
Tran Hai ◽  
Fred Bernd Oppermann-Sanio ◽  
Alexander Steinbüchel
Keyword(s):  
Aspartic Acid ◽  
Thermostable Enzyme ◽  
Exchange Chromatography ◽  
In Vitro Production ◽  
In Vitro Synthesis ◽  
Prolonged Incubation ◽  
Thermophilic Cyanobacterium ◽  
Recombinant Cells ◽  
Cyanophycin Synthetase

ABSTRACT The thermophilic cyanobacterium Synechococcus sp. strain MA19 contained the structural genes for cyanophycin synthetase (cphA) and cyanophycinase (cphB), which were identified, cloned, and sequenced in this study. The translation products of cphA and cphB exhibited high levels of similarity to corresponding proteins of other cyanobacteria, such as Anabaena variabilis and Synechocystis sp. Recombinant cells of Escherichia coli harboring cphA colinear with lacPO accumulated cyanophycin that accounted for up to 25% (wt/wt) of the dry cell matter in the presence of isopropyl-β-d-thiogalactopyranoside (IPTG). The cyanophycin synthetase was enriched 123-fold to electrophoretic homogeneity from the soluble fraction of the recombinant cells by anion-exchange chromatography, affinity chromatography, and gel filtration chromatography. The purified cyanophycin synthetase maintained the parental thermophilic character and was active even after prolonged incubation at 50°C; in the presence of ectoine the enzyme retained 90% of its activity even after 2 h of incubation. The in vitro activity of the enzyme depended on ATP, primers, and both substrates, l-arginine and l-aspartic acid. In addition to native cyanophycin, the purified enzyme accepted a modified cyanophycin containing less arginine, α-arginyl aspartic acid dipeptide, and poly-α,β-dl-aspartic acid as primers and also incorporated β-hydroxyaspartic acid instead of l-aspartic acid or l-canavanine instead of l-arginine at a significant rate. The lack of specificity of this thermostable enzyme with respect to primers and substrates, the thermal stability of the enzyme, and the finding that the enzyme is suitable for in vitro production of cyanophycin make it an interesting candidate for biotechnological processes.

Alkyl Hydrogen Phosphonate Derivatives of the anti-HIV Agent AZT may be Less Toxic than the Parent Nucleoside Analogue

1994 ◽  
Vol 5 (4) ◽  
pp. 271-277 ◽  
Author(s):  
C. McGuigan ◽  
P. Bellevergue ◽  
B. C. N. M. Jones ◽  
N. Mahmood ◽  
A. J. Hay ◽  
...  
Keyword(s):  
Nucleoside Analogue ◽  
Parent Drug ◽  
Antiviral Action ◽  
Alkyl Derivatives ◽  
Free Nucleotides ◽  
A Cell ◽  
Derivatives Of ◽  
Anti Hiv ◽  
Long Chain

Novel alkyl hydrogen phosphonate derivatives of the anti-HIV nucleoside analogue AZT have been prepared by phosphorochloridite chemistry. These materials are designed to act as labile membrane-soluble prodrugs of the bioactive free nucleotides. In vitro evaluation has revealed the compounds to have a pronounced and selective antiviral action. Short-chain (C1-C7) alkyl derivatives are more potent than the parent hydrogen phosphonate, whilst one long-chain (C18) compound is less active. In an assay that demonstrates the toxicity of the parent drug AZT, the alkyl H-phosphonates appear to be less cytotoxic, whilst retaining full antiviral activity. Lastly, the compounds are all poorly active in a cell line (JM) that is poorly responsive to AZT, indicating that they act as depot forms of the nucleoside rather than of the free nucleotide.

Cytotoxic and non-cytotoxic N-alkyl derivatives of putrescine: effect on polyamine uptake and growth of prostatic cancer cells in vitro

1987 ◽  
Vol 36 (11) ◽  
pp. 1849-1852 ◽  
Author(s):  
Warren D.W. Heston ◽  
Kyoichi A. Watanabe ◽  
Krzysztof W. Pankiewicz ◽  
Douglas F. Covey
Keyword(s):  
Cancer Cells ◽  
Prostatic Cancer ◽  
Alkyl Derivatives ◽  
Polyamine Uptake ◽  
Derivatives Of
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