Amino acid transport and metabolism in nitrogen-starved cells of Saccharomyces cerevisiae.

Nitrogen-starved yeast derepress a general amino acid permease which transports basic and hydrophobic amino acids. Although both groups of amino acids are metabolized, the derivatives of the basic amino acids are retained by the cells, whereas those of the hydrophobic amino acids are released as acidic and neutral deaminated derivatives. The release of the deaminated derivatives of the hydrophobic amino acids only occurs in the presence of glucose, which presumably produces amino acceptors. The accumulation of intracellular amino acids results in trans-inhibition of the uptake of exogenous amino acids whether the intracellular amino acid is a basic amino acid or the product of intracellular transamination from a hydrophobic amino acid. Variation of permease and transaminase activity was measured during growth under repressed (ammonia-grown) and derepressed (proline-grown) conditions. Maximum levels for both activities occurs at the mid-exponential phase.     

Novel peptide derivatives of bleomycin A5: synthesis, antitumor activity and interaction with DNA

A series of novel amino acid and peptide derivatives of bleomycin (BLM) A(5) were synthesized. All the compounds possessed significant antitumor activities in vitro against HL-60, BGC-823, PC-3MIE8, and MDA-MB-435 cell lines. Their antitumor activities against MDA-MB-435 were 10-fold higher than BLM A5. The DNA cleavage studies indicated that the hydrophobic amino acid or peptide derivatives of BLM A5 could induce higher cleavage ratio of double to single strand DNA than BLM A5. From the DNA binding studies, we found that the derivatives containing either D-conformation amino acid or basic amino acid could facilitate DNA binding of BLM.     

Studies on 2-aziridinecarboxylic acid peptides: Their reaction and uses

The reaction of 2-aziridinecarboxylic acid derivatives with several protic reagents was used to synthesize depsipeptides, dehydroamino acid derivatives, diaminopropionic acid derivatives, and phospho peptide derivatives. The reaction of N-aminoacyl-2-aziridinecarboxylic acid benzyl ester with amino acid ester induced stereoselective transacylation.     

Preparation of amino acid conjugates of betulinic acid with activity against human melanoma.

Betulinic acid has been coupled with a series of amino acids at C-28 carboxylic acid position and the toxicity of the derivatives has been evaluated against cultured human melanoma (MEL-2) and human epidermoid carcinoma of the mouth (KB) cell lines. A number of amino acid conjugates of betulinic acid showed improved water solubility as well as selective cytotoxicity. This investigation demonstrates that amino acid conjugates of betulinic acid can produce potentially important derivatives, which may be developed as antitumor agents.     

Enzymatic synthesis of dipeptide units of the D-D-configuration in aqueous media

The enzymatic synthesis of dipeptide units of the D-D-configuration in aqueous media, catalysed by muramoyl-pentapeptide carboxypeptidase (E.C.3.4.17.8), is described. Ac-L-Lys(Ac)-D-Ala-D-Lac-OH and Ac-D-Ala-OMe were used as acyl-components. Neutral, basic, and hydrophobic amino acids acting as nucleophiles were incorporated. The enzyme is stereospecific in that only the D-enantiomers of amino acids or amino acid derivatives were incorporated. As nucleophiles, the unmodified amino acids resulted in higher product yields compared with using the corresponding amino acid derivatives. Product yields ranged from 40 to 87%.     

核糖核酸酶、胰凝乳蛋白酶等蛋白质光照产生荧光物质的研究

对核糖核酸酶、胰凝乳蛋白酶等近十种蛋白质、氨基酸及其衍生物进行光照研究,发现在强紫外光照后都能产生荧光物,其发射峰的位置在400um左右.光照带芳香氨基酸残基的蛋白质形成荧光物是蛋白质的一个共同的特性.进一步分离这些蛋白荧光物时,发现这些蛋白质受到紫外光照后,有一定的破坏,包括链的断裂和某些氨基酸含量的减少.     

Synthesis and biological activity of aminophenylphosphonic derivatives of levorin

Reactions of levorin, a polyenic macrolide antibiotic, with aromatic aldehydes and hypophosphorous acid resulted in formation of its amino phenylphosphonium derivatives. Physicochemical and biological properties of the derivatives were studied. The levorin amino phenylphosphonium derivatives were shown to be low toxic and have antifungal and antiviral activities.     

Mass Fragmentographic Method for the Determination of Trace Amounts of Putative Amino Acid Neurotransmitters and Related Compounds from Brain Perfusates Collected In Vivo

Abstract: A mass fragmentographic method for the determination of trace amounts of amino acid neurotransmitter candidates from brain perfusates is described. The analytical procedure includes the measurements of glycine, β-alanine, γ-aminobutyric acid, proline, aspartic acid, and glutamic acid; αalanine, leucine, and sarcosine, undergoing gas chromatographic coelution, are detected simultaneously. Amino acids extracted from dried perfusate residues are converted to the corresponding N -pentafluoropropionyl hexafluoroisopropyl esters by a single-step procedure. Gas chromatographic separation of the amino acid derivatives is achieved on a packed glass column filled with trifluoropropylsilicone as stationary phase. The limit of detection for the different derivatives (signal-to-noise, 3:1) ranges from 50 femtomol to 1 picomol. Deuterium-labeled amino acid analogues are used as internal standards for quantitative measurements. The mass spectral characteristics of the derivatives are compared and discussed. The technique has been applied to the assay of amino acids released in vivo within the pigeon optic tectum, demonstrating the capabilities of the present analytical approach.     

Amino acid hydroxamates as inhibitors of the human enkephalin-degrading aminopeptidase

Amino acid hydroxamate derivatives inhibit the recently characterized enkephalin-degrading aminopeptidase from human blood (α-aminoacyl-peptide hydrolase, EC 3.4.11.11). The efficiency of inhibition depends on the structure of the amino acid hydroxamate employed. Amino acid hydroxamate decivatives also inhibit metalloendopeptidases and enkephalin-degrading enzymes from rat brain. The degradation of enkephalin in blood and in the brain seems to be under the control of a number of metallopeptidases: suitable amino acid hydroxamate derivatives can therefore be proposed as general inhibitors of enkephalin breakdown.     

Sensitization of Edman amino acid derivatives using the fluorescent reagent, 4-aminofluorescein

The ability to analyze amino acid derivatives at the femtomole level is one of the most interesting challenges in the field of protein microsequencing. 2-Anilino-5-thiazolinone amino acids, obtained by Edman degradation, were quantitatively derivatized with fluorescent primary amines. The most fluorescent reagent tested was 4-aminofluorescein. The amino acid derivatives sensitized with this reagent were separated using reversed-phase high-performance liquid chromatography and identified at the 100 attomole level. Incorporation of this method into the operation of a conventional automated sequencer is also described.     

The use of N-urethane-protected N-carboxyanhydrides (UNCAs) in amino acid and peptide synthesis

N-Urethane-protected N-carboxyanhydrides (UNCAs) are very reactives. They have been successfully used in peptide synthesis, in both solution and solid phase. We have demonstrated that UNCAs are interesting starting materials for the synthesis of various amino acid derivatives. Chemoselective reduction of UNCAs with sodium borohydride led the corresponding N-protected β amino alcohols. Reaction of UNCAs with Meldrum's acid, followed by cyclisation, yielded enantiomerially pure tetramic acid derivatives. Diastereoselective reduction of tetramic acid derivatives produced (4S,5S)-N-alkoxycarbonyl-4-hydroxy-5-alkylpyrrolidin-2-ones derived from amino acids, which after hydrolysis yielded statine and statine analogues. Tetramic acid derivatives could also be obtained by reaction of UNCAs with benzyl ethyl followed by hydrogenolytic deprotection and decarboxylation. UNCAs also reacted with phosphoranes to produce the ketophosphorane in excellent yields. Subsequent oxidation with oxone or with [bis(acetoxy)-iodol]-benzene produced vicinal tricarbonyl derivatives. These reactions usually proceeded smoothly and with high yields.     

Coupling of iminodiacetic acid with amino acid derivatives in solution and solid phase

The IR studies for the preactivation step of N-protected iminodiacetic acid with different coupling reagents (TCFH,TFFH, HATU, HBTU, HSTU) were reported here and showed theformation of an anhydride as an active intermediate in caseof TCFH and TFFH. The formation of a mixture of an anhydrideand an active ester (–OBt, –OAt or –OSu) were observed forHBTU, HATU or HSTU coupling reagent. Dependent on the couplingconditions, acylation of N-protected iminodiacetic acid with amino acid ester or amide derivatives in solution phase gavemono- or di-substituted iminodiacetic acid derivatives. Couplingof N-protected iminodiacetic acid with an amino acid or peptideattached to a solid support (PAL-PEG-PS or Wang resin) gave onlythe monosubstituted iminodiacetic acid derivatives.     

Amino acid analysis of collagen hydrolysates by reverse-phase high-performance liquid chromatography of 9-fluorenylmethyl chloroformate derivatives

A recently described procedure for amino acid analyses has been modified and adapted for use in quantitating the unique mixture of products commonly found in hydrolysates of the collagens. The method involves precolumn derivatization of hydrolysates with 9-fluorenylmethyl chloroformate (FMOC-CL), chromatographic separation of the derivatives and excess reagent on a reverse-phase column, and quantitation based on the fluorescent properties of the derivatives. The method takes advantage of the ease with which stable derivatives are formed with the FMOC reagent. Using a ternary gradient system, a complete amino acid analysis with good resolution of all components can be performed within 35 min. The sensitivity of the method is comparable to levels attained by other derivatives and the fluorescence response of each derivative is linear over the total range of 1-800 pmol. Given these parameters, the method allows complete amino acid analyses to be performed on 100 ng of collagen corresponding to a single picomole of a collagen chain (Mr 100,000).     

Quantitative amino acid makeup and the characteristics of the amino groups of ristomycin and the products of its partial acid hydrolysis]

The quantitative amino acid composition of ristomycin A, a glycopeptide antibiotic, peptides I-IV (from partial acid hydrolysis of the antibiotic) and their dinitrophenylic derivatives was determined. It was shown that both ristomycin and free peptides I-IV contained one residue of ristomycinic acid and one residue of actinoidinic acid, diamino-dicarbonic amino acids of the glycylphenolic type. Peptides I-IV had close molecular weights, i.e. 1100-1200 and differed from each other in the gradually increasing numbers of NH2- and COON- groups, from one in peptide I to four in peptide IV. The quantitative amino acid analysis of the dinitrophenylic derivatives of ristomycin and peptides I-IV showed that the free NH2-group in peptide I belonged to ristomycinic acid, the same as in the antibiotic, while in peptides III-IV at least one of the free NH2-groups belonged to ristomycinic acid and the other belonged to actinoidinic acid.     

Specific sulfonation of tyrosine, tryptophan and hydroxy-amino acids in peptides

1. ClSO3H in trifluoroacetic acid rapidly converts serine and threonine into O-sulfate ester derivatives while tyrosine and tryptophan are converted into arylsulfonic acids. 2. H2SO4 in trifluoroacetic acid reacts more slowly with serine, threonine and tyrosine while is not able to modify tryptophan. 3. All other amino acids are perfectly stable under the above reaction conditions. 4. Peptides containing susceptible amino acid residues are specifically converted into the corresponding sulfonated derivatives in high or quantitative yield.     

氨基酸环状衍生物的合成及抑菌活性

近年来,氨基酸及其衍生物在医药和农业上已显示有广阔的应用前景。现就近十余年来,国外文献报道的具有抗病原微生物活性的氨基酸环状衍生物作一简要概述。     

Design, synthesis and biological evaluation of novel amino acid ureido derivatives as aminopeptidase N/CD13 inhibitors

A series of amino acid ureido derivatives as aminopeptidase N (APN/CD13) inhibitors were synthesized and evaluated for their APN inhibitory activities and anti-cancer effects. The results showed that most of these amino acid ureido derivatives exhibited good inhibition against APN, several of which were better than Bestatin. The most active compound 12j (IC(50) = 1.1 μM, compared with Bestatin IC(50) = 8.1 μM) not only possessed much better APN inhibitory activity and anti-proliferation effect on cancer cells, but also exhibited significant block effect of human cancer cell invasion compared with the positive control, Bestatin. These amino acid ureido derivatives could be possibly developed as new APN inhibitors for cancer chemotherapy in the future.     

氨基酸酰胺类化合物的合成

阐述了氨基酸氨基保护的常用方法和试剂,氨基酸酰胺类化合物合成的基本原理和方法以及在合成中需要注意的问题。重点阐述了氨基酸酰胺类化合物的合成机理和合成方法。展望了氨基酸酰胺类衍生物的合成方向。     

Antioxidant activities of cysteine derivatives against lipid oxidation in anhydrous media

This study investigated antioxidant activities of cysteine derivatives of amino and carboxylic acid moieties against lipid oxidation in anhydrous acetonitrile. Only cysteine derivatives bearing free amino or carboxylate ion were found to exert potent antioxidant activities. Sequential proton loss and electron transfer-like proton shift and subsequent electron transfer (PS-ET) mechanism may facilitate the antioxidant activities of cysteine derivatives against lipid oxidation in anhydrous media.     

The stability of the o-phthalaldehyde/2-mercaptoethanol derivatives of amino acids: an investigation using high-pressure liquid chromatography with a precolumn derivatization technique

The investigation of the stabilities of o-phthalaldehyde/2-mercaptoethanol derivatives of amino acids using a precolumn reaction technique and a high-pressure liquid chromatographic procedure is reported. The amino acid derivatives are shown to be stable on the high-pressure liquid chromatography column. Optimal conditions for the development of these derivatives for their separation using this technique are recommended.