Enantioselective detoxication of optical isomers of glycidyl ethers

The detoxication of the enantiomers of glycidyl 4-nitrophenyl ether (GNPE), (?)-(R)- and (+)-(S)-GNPE, and glycidyl 1-naphthyl ether (GNE), (?)-(R)- and (+)-(S)-GNE, by rat liver glutathione transferase and epoxide hydrolase was studied. Enantioselectivity was observed with both enzymes favoring the (R)-isomers as determined by the formation of conjugate, diol, and remaining substrate measured by HPLC. Enantiomers of GNE were detoxified by cytosolic epoxide hydrolase but those of GNPE were not. Substantial nonenzymatically formed conjugates of enantiomers of GNPE were detected showing (S)-GNPE the more reactive of the pair. © 1993 Wiley-Liss, Inc.     

Pb(II)-binding capability of aminohydroxamic acids: primary hydroxamic acid derivatives of alpha-amino acids as possible sequestering agents for Pb(II)

Complexes of aminohydroxamic acids, D,L-alpha-alaninehydroxamic acid (alpha-Alaha), sarcosinehydroxamic acid (Sarha), D,L-N-methyl-alpha-alaninehydroxamic acid (N-Me-alpha-Alaha), beta-alaninehydroxamic (beta-Alaha), L-aspartic acid-beta-hydroxamic acid (Asp-beta-ha), L-glutamic acid-gamma-hydroxamic acid (Glu-gamma-ha) and L-histidinehydroxamic acid (Hisha) with lead(II) in aqueous solution were studied by pH-potentiometric, 1H NMR and electrospray ionization mass spectrometric (ESI MS) methods. The results were compared to those of a simple monohydroxamic acid, acetohydroxamic acid and the effects of the amino group, hydroxamate-N, as well as, additional side chain donors on the co-ordination mode and on the stability of the complexes formed were evaluated. It was found that the amino nitrogen atom situating in beta- or in gamma-position (beta-Alaha, Asp-beta-ha, Glu-gamma-ha) does not co-ordinate to Pb(II), only hydroxamate type chelates are formed before the hydrolytic processes. However, the amino-N in alpha-position (alpha-Alaha, Sarha, Hisha) seems to form a stable 5-membered (N,N)-type chelate together with the deprotonated hydroxamate-N above pH 6. On the other hand, the hydroxamate (O,O)-type chelate also exists. Since steric reasons do not allow the coordination of these two chelates of a molecule to the same Pb(II) ion, polynuclear complexes with mixed co-ordination modes are formed with the alpha-derivatives above pH 6. Simple hydroxamate type complexes are formed with N-Me-alpha-Alaha, where the hydroxamate-N is not able to co-ordinate. The co-ordination of the side chain imidazole of Hisha is not measurable, while a weak interaction of the side chain carboxylates of Asp-beta-ha and especially of Glu-gamma-ha can be suggested.     

Phagocidal Activity of the Hydrolyzate of Acetal Derivatives of Oxidized Spermine and Its N,N′-Dimethyl Analog

The hydrolysis of acetal derivatives of oxidized spermine, N, N′-bis (3, 3-diethoxypropyl)-1, 4-diaminobutane, and its N, N′-dimethyl analog with acid was practically complete within 1 hr. During the hydrolysis of these compounds, no detectable amounts of acrolein were formed in the reaction mixture. While the hydrolyzate of the acetal derivative of oxidized spermine potently inactivated bacteriophage T¹, that of the N, N′-dimethyl analog had little phagocidal activity.     

Analysis of penicillin V biosynthesis during fed-batch cultivations with a high-yielding strain of Penicillium chrysogenum

Metabolites (both intra- and extracellular) involved in penicillin biosynthesis were measured during fed-batch cultivations with a high-yielding strain of Penicillium chrysogenum. The fed-batch cultivations were carried out on a complex medium containing corn steep liqour. Three distinct phases were observed: (a) a rapid growth phase where free amino acids present in the medium are metabolized, (b) a linear growth phase, and (c) a stationary phase. The specific penicillin production (r _p) is initially high and, during the rapid growth phase, it increases slightly. During the linear growth phase r _p is approximately constant [4–6 mg penicillin V (g dry weight)^–1 h^–1 depending on the operating conditions], whereas it decreases during the stationary phase. During the cultivations the tripeptide Aad-Cys-Val (the first metabolite in penicillin biosynthesis) and 8-hydroxypenillic acid (formed by carboxylation of 6-aminopenicillanic acid, 6-APA) were found to accumulate in the medium, whereas the concentrations of isopenicillin N and 6-APA were found to be approximately constant and low. About 3% of the Aad-Cys-Val formed in the first step of the penicillin biosynthetic pathway is lost to the medium and 4% of the isopenicillin N formed in the second step of the pathway is lost as extracellular isopenicillin N, 6-APA or 8-hydroxypenillic acid. Also the cyclic form of -aminoadipic acid, 6-oxopiperidine-2-carboxylic acid, was found to accumulate in the medium and it was found to be formed in an approximately constant ratio to penicillin V of 6 mol/100 mol.     

Phage mediated horizontal transfer of the sopE1 gene increases enteropathogenicity of Salmonella enterica serotype Typhimurium for calves

Anaerobic fungi are an important component of the cellulolytic ruminal microflora. Ammonia alone as N source supports growth, but amino acid mixtures are stimulatory. In order to evaluate the extent of de novo synthesis of individual amino acids in Piromyces communis and Neocallimastix frontalis, isotope enrichment in amino acids was determined during growth on (15)NH(4)Cl in different media. Most cell N (0.78 and 0.63 for P. communis and N. frontalis, respectively) and amino acid N (0.73 and 0.59) continued to be formed de novo from ammonia when 1 g l(-1) trypticase was added to the medium; this concentration approximates the peak concentration of peptides in the rumen after feeding. Higher peptide/amino acid concentrations decreased de novo synthesis. Lysine was exceptional, in that its synthesis decreased much more than other amino acids when Trypticase or amino acids were added to the medium, suggesting that lysine synthesis might limit fungal growth in the rumen.     

The biological detoxication of hormone herbicides in soil

Summary (1) The results of experiments on the continuous perfusion of aerated solutions of the herbicides 2,4-dichlorophenoxyacetic acid (2,4-D), 2, Methyl-4, chlorophenoxyacetic acid (MCPA) and 2,4,5-trichlorophenoxyacetic acid (2,4,5-T) through garden soil indicate that the kinetics of their breakdown are essentially similar.(2) Three phases can be distinguised: (a) an immediate initial adsorption onto soil colloids amounting to 0.167±0.035 mg per g dry soil, (b) a lag phase of varying duration in which there is little or no disappearance of herbicide, (c) a final phase of rapid complete detoxication. Such enriched soils detoxicate subsequent perfusions with the same herbicide molecule at a constant high rate. Enrichment times for 2,4-D, MCPA and 2,4,5-T are roughly of the order or 14, 70 and 270 days respectively.(3) This indirect evidence, from kinetics of detoxication, of the development of a bacterial flora adapted to herbicide breakdown, is strongly supported by experiments in which the detoxicating activity of such enriched soils was completely destroyed by low concentrations (0.01%) of the bacterial poison, sodium azide.(4) Attempts to isolate in pure culture the 2,4-D-decomposing organism were successful. Preliminary classification work relegates the organism to the Bacterium globiforme group. Further confirmatory work is required.(5) Cross perfusion experiments in which 2,4-D enriched soils were perfused with MCPA and vice versa indicate that both can detoxicate the other analogue, although at a somewhat lower rate than the soil directly enriched with that analogue.(6) 2,4-D enriched soil will not detoxicate 2,4,5-T although some activity may be temporarily induced by an intermediate perfusion with MCPA.     

Metabolic fate of nicotinamide in higher plants

Metabolism of [carbonyl-¹⁴C]nicotinamide was surveyed in various plant materials including the model plants, Arabidopsis thaliana , Oryza sativa and Lotus japonicus . In all plants studied, nicotinamide was used for the pyridine (nicotinamide adenine) nucleotide synthesis, probably after conversion to nicotinic acid. Radioactivity from [carbonyl-¹⁴C]nicotinamide was incorporated into trigonelline (1- N -methylnicotinic acid) and/or into nicotinic acid 1 N -glucoside (Na-Glc). Trigonelline is formed mainly in leaves and cell cultures of O. sativa and L. japonicus and in seedlings of Trifolium incarnatum , Medicago sativa and Raphanus sativus . Trigonelline synthesis from nicotinamide is generally greater in leaves than in roots. Na-Glc was formed as the major nicotinic acid conjugate in A. thaliana and in tobacco Bright Yellow-2 cells. In seedlings of Chrysanthemum coronarium and Theobroma cacao , both trigonelline and Na-Glc were synthesized from [carbonyl-¹⁴C]nicotinamide. Trigonelline is accumulated in some seeds, mainly Leguminosae species. The pattern of formation of the nicotinic acid conjugates differs between species and organs.     

Identification of sequence mutations affecting hemagglutinin specificity to sialic acid receptor in influenza A virus subtypes

The attachment of the hemagglutinin protein of the H1N1 subtype of the pandemic influenza A virus to the sialic acid receptor Sia(α2-6)Gal has contributed to the ability of the virus to replicate in the human body and transmit among humans. In view of the pandemic caused by the replication and transmission of the H1N1 virus, more studies on the specificity of hemagglutinin towards sialic acid and how it affects the replication and transmission ability of this virus among humans are needed. In this study, we have applied sequence, structural and functional analyses to the hemagglutinin protein of the pandemic H1N1 virus, with the aim of identifying amino acid mutation patterns that affect its specificity to sialic acid. We have also employed a molecular docking method to evaluate the complex formed between hemagglutinin protein and the sialic acid receptor. Based on our results, we suggest two possible mutation patterns, namely (1) positions 190 and 225 from glutamic acid and glycine to aspartic acid (E190D in A/Brevig Mission/1/18 (H1N1), A/New York/1/18(H1N1) and A/South Carolina/1/1918(H1N1) and G225D in A/South Carolina/1/1918(H1N1), A/South Carolina/1/1918(H1N1), and A/Puerto Rico/8/34(H1N1)), and (2) positions 226 and 228 from glutamine and glycine to leucine and serine, respectively (Q226L and G228S in A/Guiyang/1/1957(H2N2), A/Kayano/57(H2N2), A/Aichi/2/1968(H3N2), A/Hong Kong/1/1968(H3N2) and A/Memphis/1/68(H3N2)) that can potentially contribute to the specificity of hemagglutinin to Sia(α2-6)Gal, thereby enabling the replication and transmission of virus within and among humans.     

Detoxications in peripatus. Sulphate, phosphate and histidine conjugations

Phenols were detoxified in the Onycophoran Peripatoides novaezealandiae by conjugation with sulphuric acid and phosphoric acid, but no evidence for a glycoside detoxication could be found. [(14)C]Benzoic acid was metabolized in 24h to N(2)-benzoyl-l-histidine, which was identified by electrophoresis, chromatography and dilution analysis. Similar conjugates were formed with p-aminobenzoic acid and p-nitrobenzoic acid. In longer-duration experiments further unidentified metabolites were formed, two of which appeared to result from the further metabolism of the histidine conjugate.     

Study of drug resistance of chicken influenza A virus (H5N1) from homology-modeled 3D structures of neuraminidases

The spread of highly pathogenic H5N1 influenza virus in many Asian and European countries as well as its drug-resistance have raised serious worldwide concerns. In this paper, the structure-activity relationship between NA (neuraminidase) and its three inhibitors (DANA, zanamivir, and oseltamivir) was investigated. A homology model of H5N1-NA (BAE46950), which is the first reported oseltamivir-resistance virus strain, and the 108 homology-modeled 3D structures of chicken influenza H5N1 NAs downloaded from the website at , formed the molecular structural basis for the drug-resistance study. The multiple sequence and structure alignment for these NAs indicated that 11 functional residues were highly conserved except for AAF02313 with the mutated virus strain. However, the framework residues have remarkable mutations from N9-NA to H5N1-NA, and a few mutated residues were observed in different H5N1-NAs. A partially hydrophobic site S5 (formed by Ala246 and Thr247) in N9-NA is changed to a hydrophilic site (formed by Ala227 and Asn228) in H5N1-NA, while a hydrophilic site S6 (formed by Asn346 and Asn347) in N9-NA was replaced by a hydrophobic site (formed by Ala323 and Tyr324). All these mutations might be the reason for the oseltamivir-resistance by some H5N1 viruses. In order to find the possible drug-resistant H5N1 virus, similarity analysis was performed using the BAE46950 sequence as the benchmark template, and 21 sequences were found from the database of the 108 H5N1 NAs that had over 95% sequence similarity with BAE46950.     

N5-(1-carboxyethyl)-ornithine, a new amino acid from the intracellular pool of Streptococcus lactis.

Intracellular concentrations of amino acids were determined in cells of Streptococcus lactis 133 during growth in complex, spent, and chemically defined media. Glutamic and aspartic acids represented the major constituents of the amino acid pool. However, organisms grown in spent medium or in defined medium supplemented with ornithine also contained unusually high levels of two additional amino acids. One of these amino acids was ornithine. The second compound exhibited properties of a neutral amino acid by coelution with valine from the amino acid analyzer. The compound did not, however, comigrate with valine or any other standard amino acid by two-dimensional thin-layer chromatography. The unknown amino acid was purified by paper and thin-layer chromatography, and its molecular structure was determined by 1H and 13C nuclear magnetic resonance spectroscopy. This new amino acid was shown to be N5-(1-carboxyethyl)-ornithine. The 14C-labeled compound was formed by cells of S. lactis 133 during growth in spent medium or defined medium containing [14C]ornithine. Formation of the derivative by resting cells required ornithine and the presence of a metabolizable sugar. N5-(1-Carboxyethyl)-ornithine was synthesized chemically from both poly-S-ornithine and (2S)-N2-carbobenzyloxy-ornithine as a 1:1 mixture of two diastereomers. The physical and chemical properties of the amino acid purified from S. lactis 133 were identical to those of one of the synthetic diastereomers. The bis-N-trifluoroacetyl-di-n-butyl esters of the natural and synthetic compounds generated identical gas chromatography-mass spectrometry spectra. A mechanism is suggested for the in vivo synthesis of N5-(1-carboxyethyl)-ornithine, and the possible functions of this new amino acid are discussed.     

Synthesis and secondary structural studies of penta(acetyl-Hmb)A beta(1-40).

The Fmoc solid phase synthesis of A beta(1-40), a strongly aggregating peptide found in Alzheimer's disease brain, was performed using 2-hydroxy-4-methoxybenzyl (Hmb) backbone amide protection. Hmb-Gly residues were incorporated using N(alpha)-Fmoc-Hmb-Gly-OH rather than N,O-bisFmoc-Hmb-Gly-OPfp. Amino acid acylation of the sterically hindered Hmb-amino acids was monitored using 'semi-on-line' MALDI-TOF-MS in a novel application of this technique which significantly simplified the successful incorporation of these residues. Standard coupling conditions in N,N-dimethylformamide (DMF) were used throughout the synthesis. Comparative structural studies of acetyl-Hmb-protected and native A beta(1-40) were performed to investigate the structural basis of Hmb-mediated disaggregation. The incorporation of backbone amide protection was observed by circular dichroism spectroscopy and gel electrophoresis to strongly affect the solution structure of A beta(1-40). Despite the reported structure-breaking activity of Hmb groups, penta(acetyl-Hmb)A beta(1-40) was found to adopt both alpha-helix and intermolecular beta-sheet conformations. In 100% TFE a mixed alpha-helix/random coil structure was formed by the protected peptide indicating reduced alpha-helical propensity relative to A beta(1-40). The protected peptide formed beta-sheet structures in aqueous buffer. Gel electrophoresis indicated that, unlike native A beta(1-40), penta(acetyl-Hmb)A beta(1-40) did not form large aggregate species.     

Novel amides modified rupestonic acid derivatives as anti-influenza virus reagents

In spired by the important role of amide groups of anti-influenza drugs oseltamivir, zanamivir and peramivir in bioactivity, a series of novel amides modified rupestonic acid derivatives were designed and synthesized. The absolute configuration of critical intermediate bearing chloride with newly formed stereocenter was confirmed by X-ray crystallographic analysis. And all new compounds were evaluated for their in vitro inhibitory activities against influenza A (H1N1 and H3N2) and influenza B viruses. The bioassay results showed that 5h with 4-fluorbenzylsulfonyl modified to 2 position of methyl rupestonate displayed the highest activity against influenza A (H1N1 and H3N2) viruses, even stronger than reference drugs oseltamivir and ribavirin (RVB), and might be recommended as a lead compound to further develop the new anti-influenza reagent.     

Simultaneous determination of phytohormones containing carboxyl in crude extracts of fruit samples based on chemical derivatization by capillary electrophoresis with laser-induced fluorescence detection

An efficient and sensitive capillary electrophoresis with laser-induced fluorescence detection (CE-LIF) method has been developed for the simultaneous determination of phytohormones containing carboxyl group, including gibberellic acid, indole-3-acetic acid, abscisic acid, jasmonic acid, indole butyric acid, 1-naphthalene acetic acid and 2,4-dichloro-phenoxy acetic acid, based on the chemical derivatization with 6-oxy-(acetypiperazine) fluorescein. Using 1-ethyl-3-(3-dimethylaminopropyl) carbodiimide as the condensing reagent, the derivatization reaction completed at 60°C in 60 min and the derivatization limits could reach 20 nmol L(-1). The formed derivatives of seven phytohormones have been separated and quantified within 20 min. The linearity was found in the range of 0.01-1 μmol L(-1) and the limits of detection were 1.6-6.7 nmol L(-1) (S/N=3). The proposed method has been applied to analyze the crude extract of 0.5 g banana samples directly without further purification and the recoveries varying from 90.7 to 106.1%.     

Analysis of 13C and 15N CPMAS NMR-spectra of soil organic matter and composts

15N and 13C CPMAS spectra of composted plants are presented. The plants (L. rigidium and Zea mays) were grown in 15N enriched medium and fermented for several months until an approx. 80% of the dry matter was lost. In all 15N spectra the secondary amide/peptide peaks at 87 ppm contributes more than 80% of the total intensity. No new 15N peaks are formed during the fermentation process. Older attempts to assign a significant fraction of humic acid nitrogen to heteroaromatic structures formed in the fermentation process are thus most probably wrong.     

N6-(1-carboxyethyl)lysine formation by Streptococcus lactis. Purification, synthesis, and stereochemical structure

During growth in an arginine-deficient (chemically defined) medium, cells of Streptococcus lactis K1 formed significant amounts of a previously undetected ninhydrin-positive compound. This intracellular compound did not cochromatograph with any of a wide range of amino acids or amino acid analogs tested. However, by two-dimensional thin layer chromatography, the unknown compound migrated close to the recently discovered N5-(1-carboxyethyl)ornithine (Thompson, J., Curtis, M. A., and Miller, S. P. F. (1986) J. Bacteriol. 167, 522-529; Miller, S. P. F., and Thompson, J. (1987) J. Biol. Chem. 262, 16109-16115). The purified compound behaved as a neutral amino acid and eluted between valine and methionine in the amino acid analyzer. The results of 1H NMR spectroscopy suggested the presence of a lysine backbone and a coupled methyl-methine unit in the molecule, and 13C NMR showed that there were nine carbon atoms, of which two (C-1 and C-7) were carboxyl carbons. The simplest structure compatible with the physicochemical data was that of an alkylated derivative of lysine. The identity of this new amino acid, N6-(1-carboxyethyl)lysine, was confirmed by chemical synthesis. In vivo labeling experiments conducted using L[U-14C]lysine and [epsilon-15N]lysine showed that exogenous lysine served as the precursor of intracellular N6-(1-carboxyethyl)lysine and that the epsilon-amino N atom was conserved during biosynthesis of the lysine derivative. Of the two possible diastereomers (2S,8S or 2S,8R) of N6-(1-carboxyethyl)lysine, comparative 13C NMR spectroscopy established that the amino acid produced by S. lactis K1 was exclusively of the 2S,8S configuration.     

Reaction of epichlorohydrin with adenosine, 2'-deoxyadenosine and calf thymus DNA: identification of adducts

Epichlorohydrin (a probable human carcinogen) was allowed to react with adenosine and the adducts were characterized by NMR and UV spectroscopy, and mass spectrometry. The adduct initially formed was 1-(3-chloro-2-hydroxypropyl)-adenosine, which subsequently ring closures to 1,N(6)-(2-hydroxypropyl)-adenosine at neutral and basic conditions. At acid conditions, the N-1 adduct undergoes a slow deamination to yield 1-(3-chloro-2-hydroxypropyl)-inosine. Minor adducts identified were 7-(3-chloro-2-hydroxypropyl)-adenosine and 3-(3-chloro-2-hydroxypropyl)-adenosine which are easily deglycosylated, and an adduct where the epichlorohydrin residue was attached to the sugar moiety of adenosine. A diadduct, 1,N(6)-(2-hydroxypropyl)-N(6)-(3-chloro-2-hydroxypropyl)-adenosine was also identified. The reaction of epichlorohydrin with calf thymus DNA gave 1,N(6)-(2-hydroxypropyl)-deoxyadenosine and 3-(3-chloro-2-hydroxypropyl)-adenine (major adduct).     

Pheno-and genotyping of a placental detoxication system in ecologically unfavorable regions of Ukraine

During 1991-1993 period a study of detoxifying activity of the fetoplacental barrier and genotyping of the major detoxifying enzymes in it (CYP1A1 Ile462Val, GSTP1 Ile104Val, GSTM1 present/absent) was undertaken in different regions of Ukraine that were radioactively contaminated with summary effective equivalent annual expositional doses (SEEAED approximately 1.7 mSv (Group I) and 0.1-0.4 mSv (Group III), chemically polluted Zaporizzhia, monitored for ambient levels of benzo(a)pyrene (BP) (Group II) and Poltava that was judged as "clean" one (Group IV). Glutathione-S-transferase (GSTase) and glutathionereductase (GSSG-Rase) activities of cytosol and concentration of thiobarbituric acid reacting compounds (TBA-reactants) and reduced low-molecular weight thiols (rLMW thiols) were used as phenotype parameters. Cytosolic GSTase activities were nearly two times less in the samples from radioactively contaminated area (Group I, SEEAED approximately 1.7 mSv) and in chemically polluted area (Group II, mean BP level 12.3 ng/m3), compared with the groups III and IV. The highest level of TBA-reactants indicative of lipid peroxidation in response to radiation was observed in Group I, while the lowest level in Group IV. The level of rLMW thiols was 2.5-4 times more in Group II comparative with Groups I, III and IV. The frequency of the genotypes in all the investigated samples corresponds to that reported for Caucasians. For the combined exposure groups, individuals with the CYP1A1 (Ile462Val) genotype (n = 5) had significantly higher levels of GST, GSSG-R and TBA reacting compounds compared to individuals with the Ile462Ile genotype (n = 14 for TBA-reactants and n = 24--for GST and GSSG-R). Despite the challenge of small numbers of individuals, stratification by exposure group for Groups I, II and III indicated significantly higher GST levels in CYP1A1 (Ile462Val) variants from Groups II and III (n = 3) compared to the Ile462Ile variants (n = 17). The data demonstrate contributions by both exposure and genotype on the detoxification of radiation and chemical damage in the human placenta.     

3-Aminopyrrolidine-4-carboxylic acid as versatile handle for internal labeling of pyrrolidinyl PNA

Conformationally restricted pyrrolidinyl PNAs with an α/β-dipeptide backbone consisting of a nucleobase-modified proline and a cyclic five-membered amino acid spacer such as (1S,2S)-2-aminocyclopentanecarboxylic acid (ACPC) (acpcPNA) can form very stable hybrids with DNA with high Watson-Crick base pairing specificity. This work aims to explore the effect of incorporating 3-aminopyrrolidine-4-carboxylic acid (APC), which is isosteric to the ACPC spacer, into the acpcPNA. It is expected that the modification should not negatively affect the DNA binding properties, and that the additional nitrogen atom in the APC should provide a handle for internal modification. Orthogonally-protected (N(3)-Fmoc/N(1)-Boc and N(3)-Fmoc/N(1)-Tfa) APC monomers have been successfully synthesized and incorporated into the acpcPNA by Fmoc-solid-phase peptide synthesis. T(m), UV and CD spectroscopy confirmed that the (3R,4S)-APC could substitute the (1S,2S)-ACPC spacer in the acpcPNA with only slightly decreasing the stability of the hybrids formed between the modified acpc/apcPNA and DNA. In contrast, the (3S,4R) enantiomer of APC caused substantial destabilization of the hybrids. Furthermore, a successful on-solid-support internal labeling of the acpc/apcPNA via amide bond formation between pyrene-1-carboxylic acid or 4-(pyrene-1-yl) butyric acid and the pyrrolidine nitrogen atom of the APC spacer has been demonstrated. Fluorescence properties of the pyrene-labeled acpc/apcPNAs are sensitive to their hybridization states and can readily distinguish between complementary and single-mismatched DNA targets.     

Enhanced efficiency due to the use of achiral additives in the optical resolution of 1-phenylethylamine by its glutaric acid derivative

Racemic 1-phenylethylamine was optically resolved by its own derivative formed with glutaric acid namely (+)-(R)-N-(1-phenylethyl)glutaramic acid. The amide acid resolving agent was synthesized from (+)-(R)-1-phenylethylamine by N-derivatization. The glutaric acid derivative was the next in a homologous series of dicarboxilic acid derivatized resolving agents of racemic 1-phenylethylamine. Resolution results obtained with the oxalic, malonic, and succinic acid derivatives were previously discussed(1). Each of the above derivative resolving agents could be successfully applied as resolving agents of 1-phenylethylamine. The efficiency of the present optical resolution using (+)-(R)-N-(1-phenylethyl)glutaramic acid resolving agent was remarkably inferior to the results obtained by its shorter chained homologues(1). Use of achiral additives, like urea, thiourea, N-methylurea, and N,N'-dimethylurea caused large increase in the efficiency of the resolution by (+)-(R)-N-(1-phenylethyl)glutaramic acid resolving agent. Precipitated salts obtained in the resolutions performed in the presence of the additives were investigated by thermoanalysis, X-ray powder diffraction, and optical microscopy. Based on the analytical data, the improvement of the resolution results was attributed to the influence of the additives on the crystal nucleation processes of the diasteromeric salts.