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PubMed1995

Analysis of double-stranded DNA by capillary electrophoresis with laser-induced fluorescence detection using the monomeric dye SYBR green I.

The monomeric fluorescent dye, SYBR Green I, was investigated and compared with the dyes YO-PRO-1 and thiazole orange (TO) for their application in capillary electrophoresis (CE) with laser-induced fluorescence (LIF) detection of double-stranded DNA (dsDNA). DNA fragments were injected by hydrodynamic pressure and separated in a replaceable matrix of hydroxypropyl methylcellulose. For all 3 dyes, optimal concentrations were established and efficient separations of DNA fragments ranging in size from 75 to 12216 bp were obtained. The most promising results in terms of linear detection range were achieved with SYBR Green I. At the optimal dye concentration, fluorescence intensity versus DNA concentration was linear over more than three orders of magnitude (4 pg/microliters to 30 ng/microliters). Limit of detection (LOD) with SYBR Green I was approximately 80 fg of dsDNA (240 zmol of a 200-bp fragment). Similar LOD was obtained with YO-PRO-1, whereas TO resulted in lower sensitivity. Precision in both fluorescence intensity and migration time was high (relative standard deviation, RSD < 3.6%; n = 10) for dsDNA fragments complexed with SYBR Green I. In conclusion, SYBR Green I is fluorescent dye well suited for efficient separation and quantitative, sensitive, and precise determination of dsDNA by CE-LIF.

Benzothiazoles↗
PubMed1999

Neuroprotective effects of kynurenine-3-hydroxylase inhibitors in models of brain ischemia.

The neuroprotective effects of two kynurenine hydroxylase inhibitors, (m-nitrobenzoyl)-alanine (mNBA) and 3,4-dimethoxy-[-N-4-(nitrophenyl)thiazol-2yl]-benzenesulfona mide (Ro 61-8048), were studied in vitro and in vivo. In organotypic hippocampal slice cultures deprived of oxygen and glucose, these inhibitors significantly reduced neuronal damage. In gerbils subjected to bilateral carotid occlusion for 5 min, the administration of mNBA (400 mg/kg i.p., 3 times) or Ro 61-8048 (40 mg/kg i.p., 3 times) dramatically decreased the percentage of damaged pyramidal neurones in the hippocampal CA1 region. Finally, in rats with permanent occlusion of the middle cerebral artery, mNBA (200-400 mg/kg i.p.) and Ro 61-8048 (40 mg/kg i.p.) administration reduced the infarct volume. Our results demonstrate that ischemic neuronal damage may be significantly decreased by inhibiting kynurenine hydroxylase.

Alanine↗
PubMed1996

Physical and structural characterization of yersiniophore, a siderophore produced by clinical isolates of Yersinia enterocolitica.

Clinical isolates of Yersinia enterocolitca, which belong to mouse-lethal serotypes, produce the siderophore yersiniophore. Siderophore production was shown to be iron regulated and to reach maximum production in late log phase. Yersiniophore is a fluorescent siderophore with maximum excitation at 270 nm and a major emission peak at 428 nm. Absorption maxima were seen at 210 and 250 nm with a low broad peak from 280 to 320 nm. Purification of unchelated yersiniophore for structural analysis was made difficult by low yields (1-2 mg mg-1), and susceptibility to acid hydrolysis, oxidation and possibly polymerization. Yersinophore was therefore purified as an Al3+ chelate, which was found to be stable in solution for several weeks. To purify Al(3+)-yersinophore, unchelated yersiniophore was first extracted from culture supernatants with dichloromethane, concentrated by rotary evaporation and adsorbed to a DEAE-sephacel column. Al(3+)-yersiniophore was eluted with 0.01 M AlCl3 and further purified by HPLC. The structure was established by a combination of elemental analysis, high resolution mass spectrometry and two-dimensional NMR experiments. Yersiniophore is a phenolate-thiazole siderophore with the formula C21H24N3O4S3Al and a molecular weight of 505.07404 when chelated to Al3+. The structure of yersiniophore was determined to be closely related to the structures of pyochelin, produced by Pseudomonas aeruginosa, and anguibactin, produced by Vibrio anguillarum.

Aluminum↗
PubMed1992

Alpha 2-adrenoceptor modulation of rat ventral hippocampal 5-hydroxytryptamine release in vivo.

The putative existence of a functional alpha 2-adrenoceptor-mediated modulation of 5-HT release in vivo from serotonergic neuronal terminals in the ventral hippocampus was investigated using intracerebral microdialysis in chloral hydrate-anaesthetised rats. The alpha 2-adrenoceptor agonist clonidine (0.01-0.3 mg/kg, SC) dose-dependently decreased the 5-HT output. The response to clonidine was antagonized by systemic or local administration of the alpha 2-adrenoceptor antagonist idazoxan (0.1 mg/kg, SC, or 10 mumol/l, via the dialysis perfusion medium). Similarly, the 5-HT release-suppressing response to the thiazole alpha 2-adrenoceptor agonist jingsongling (0.1 mg/kg, SC) was blocked by idazoxan (0.1 mg/kg, SC). The mixed beta-adrenoceptor/5-HT1 receptor antagonist pindolol (8.0 mg/kg, SC) did not affect the clonidine-induced reduction of 5-HT release. Tyrosine hydroxylase inhibition by means of alpha-methyl-para-tyrosine (alpha-MT; 250 mg/kg, IP) caused a drastic reduction (greater than 80%) in dialysate 3,4-dihydroxyphenyl acetic acid (DOPAC) output but did not affect the 5-HT output per se over 3 h post-injection. Nor did the alpha-MT pretreatment prevent, but instead significantly enhanced, the 5-HT release-suppressing effect of clonidine. The results demonstrate that the release of 5-HT from serotonergic nerve terminals in rat ventral hippocampus in vivo is modulated by alpha 2-adrenoceptors, probably both by heteroreceptors on the axon terminals of the serotonergic neurones and by other alpha 2-adrenoceptor sites situated pre- and/or postsynaptic to the noradrenergic terminals. Our results also suggest that while functionally operative, these sites may receive little physiological tone, at least in chloral hydrate-anaesthetised rats.

Adrenergic alpha-Antagonists↗
PubMed1994

Release-inhibiting alpha 2-adrenoceptors at serotonergic axons in rat and rabbit brain cortex: evidence for pharmacological identity with alpha 2-autoreceptors.

The pharmacological properties of the presynaptic alpha 2-adrenoceptors modulating the release of serotonin in rat and rabbit brain cortex (alpha 2-heteroreceptors) were compared with the properties of presynaptic alpha 2-autoreceptors in the same brain area. Brain cortex slices were preincubated with [3H]-serotonin or [3H]-noradrenaline and then superfused and stimulated by brief high-frequency pulse trains. The alpha 2-adrenoceptor agonist bromoxidine reduced the electrically evoked overflow of tritium in experiments with both [3H]-noradrenaline and [3H]-serotonin and in brain slices from either species. The antagonists phentolamine, idazoxan, (+)-mianserin, rauwolscine, 5-chloro-4-(1-butyl-1,2,5,6-tetrahydropyridin-3-yl)-thiazole-2-ami ne (ORG 20350), 2-(2,6-dimethoxyphenoxyethyl)amino-methyl-1,4-benzodioxane (WB 4101), (-)-mianserin and corynanthine caused parallel shifts of the concentration-inhibition curves of bromoxidine to the right. Negative logarithms of antagonist dissociation constants pKd were calculated from the shifts. In the rat, the alpha 2-autoreceptor pKd value of each single antagonist was similar to its alpha 2-heteroreceptor pKd value, maximal difference 0.4, giving a close correlation, r = 0.97 (P < 0.001). In the rabbit equally, the alpha 2-autoreceptor pKd value of each single antagonist was similar to its alpha 2-heteroreceptor pKd value, maximal difference 0.4, again yielding a close correlation, r = 0.96 (P < 0.001). However, antagonist pKd values at rat alpha 2-autoreceptors differed from those at rabbit alpha 2-autoreceptors, r = 0.70 (P > 0.05), and antagonist pKd values at rat alpha 2-heteroreceptors differed from those at rabbit alpha 2-heteroreceptors, r = 0.64 (P > 0.05).(ABSTRACT TRUNCATED AT 250 WORDS)

Adrenergic alpha-Agonists↗
PubMed1991

Inhibition of ex-vivo PAF-induced platelet aggregation by the PAF-antagonist RP 48740: relationship to plasma concentrations in healthy volunteers.

RP 48740, 3-(3-pyridyl)-1H,3H-pyrrolo [1,2-c] thiazole-7-carboxamide, a specific competitive PAF-receptor antagonist in vitro, was given to 29 healthy male volunteers for 7 days. Plasma drug concentrations and ex-vivo PAF-induced platelet aggregation were assessed on Days 1, 4, and 7. RP 48740 had linear pharmacokinetics after single and repeated doses. It caused stable inhibition of PAF-induced platelet aggregation in a dose-dependent manner. The effect disappeared within 24 h, even after 7 days of repeated doses. The effect of RP 48740 displayed a sigmoidal relation to the plasma drug concentration; I50 2.3 (0.3) mg.l-1. There were no clinical or biological adverse reactions to RP 48740 during the study.

Administration, Oral↗
PubMed1990

Widespread occurrence of 2-acetylthiazole-4-carboxylic acid in biological material.

2-Acetylthiazole-4-carboxylic acid was shown to be widely distributed in all organisms tested, which included members of the eukaryotes, archaebacteria, and eubacteria. This thiazole, which was identified and quantitated as the methyl ester methoxyamine derivative, was found in these organisms at levels of from 27 to 1100 nmol/g dry weight (d.wt) of tissue. On the basis of its widespread occurrence, the levels at which it occurs in these organisms, and its chemical structure, which contains a reactive carbonyl group, it is proposed that this compound is a previously undescribed coenzyme.

Animals↗
PubMed1986

Binding of [3H]ICIA 5165, an H2-receptor antagonist to guinea pig gastric mucosa.

ICIA 5165, 2-guanidino-4-[4-(2-cyano-3-methylguanidino)butyl] thiazole, a selective histamine H2-receptor antagonist was radiolabelled with tritium to a specific activity of 50.8 Ci/mmol for use in binding studies. Radiolabelling did not impair bioactivity. Binding characteristics of [3H]ICIA 5165 to guinea pig gastric mucosa were determined. Ligand binding was rapid, reaching equilibrium within five minutes at 0 degrees C, reversible and saturable. Specific [3H]ICIA 5165 binding had an equilibrium dissociation constant of 1.29 X 10(-8) M, determined by Scatchard plot analysis, and of 1.02 X 10(-8) M, calculated from the ratio of the dissociation to association rate constants. A Hill number, nH, of 1.02 was determined for the specific binding component. Specific binding of [3H]ICIA 5165 to gastric mucosal supernatant was not inhibited by methapyrilene, diphenhydramine, mepyramine, d-chlorpheniramine or l-chlorpheniramine (all at 10(-7) M), or by atropine or propranolol (both at 10(-6) M). Specific [3H]ICIA 5165 binding was inhibited in a concentration dependent manner by non-radioactive ICIA 5165 and tiotidine, as well as by a variety of other agents, with H2 agonist or H2 antagonist properties. In competition experiments, however, difficulties encountered in accurately defining the degree of specific binding indicate some reservation should be observed in interpreting these results.

Animals↗
PubMed1987

Pharmacologic characterization of the antiinflammatory properties of a new dual inhibitor of lipoxygenase and cyclooxygenase.

SK&F 86002 [6-(4-fluorophenyl)2,3-dihydro-5-(4-pyridinyl)imidazo (2,1-b)thiazole], a dual inhibitor of arachidonic acid metabolism, administered orally to rats prevented the development of carrageenan-induced edema, immune- and nonimmune-mediated inflammation of adjuvant-induced arthritis (AA) and reduced established inflammation in AA and collagen type II-induced arthritis. A similar profile of activity was observed following treatment with the cyclooxygenase inhibitor, indomethacin. However, unlike other nonsteroidal antiinflammatory drugs, SK&F 86002 exhibited antiinflammatory activity in inflammation models that are insensitive to cyclooxygenase inhibitors such as the established inflammation in carrageenan-induced edema and the edema induced by arachidonic acid and platelet activating factor. Moreover, SK&F 86002, but not indomethacin, inhibited the immune-mediated inflammatory responses evoked in sensitized animals by challenge with purified protein derivative. In addition, SK&F 86002 produced dose-related analgesia in mice, which was not reversed by the narcotic antagonist, naltexone. SK&F 86002 thus represents an orally active antiarthritic and analgesic compound with novel antiinflammatory properties.

Administration, Oral↗
PubMed1992

Islet cell metabolism is reflected by the MTT (tetrazolium) colorimetric assay.

Insulin secretion depends critically on glucose metabolism. We investigated whether a rapid viability test could be established for assessing glucose metabolism in insulin secreting cells. The MTT (C,N-diphenyl-N'-4,5-dimethyl thiazol-2-yl tetrazolium bromide) colorimetric assay (reduction of tetrazolium salt to formazan) was applied to rat islets and rat insulinoma cell lines. It was found that the rate of formazan production correlated with glucose oxidation and glucose utilization at glucose concentrations which also stimulated insulin secretion. In differentiated insulinoma INS-1 cells, salt reduction paralleled the insulin release at glucose concentrations of up to 8.3 mmol/l. The glucose-induced formazan production in INS-1 cells and islets was abolished by exposure to the Beta-cell cytotoxic agents, streptozotocin or alloxan. The MTT assay thus provides a convenient tool for the rapid assessment of Beta-cell metabolism and viability.

Alloxan↗
PubMed2003

Effects of NRA0045, a novel potent antagonist at dopamine D4, 5-HT2A, and alpha1 adrenaline receptors, and NRA0160, a selective D4 receptor antagonist, on phencyclidine-induced behavior and glutamate release in rats.

RATIONALE: Administration of phencyclidine (PCP) to animals produces abnormal behavior such as hyperlocomotion, stereotyped behavior, and ataxia; this abnormal behavior is only weakly blocked by dopamine D(2) receptor antagonists. This study examined the effects of a novel thiazole derivative, NRA0045 which potently antagonizes not only dopamine D(4) receptors but also 5-HT(2A) and alpha(1) adrenaline receptors, and NRA0160, a selective dopamine D(4) receptor antagonist, on PCP-induced abnormal behavior, and accompanying increases in extracellular levels of glutamate in the medial prefrontal cortex. Furthermore, this study compared the effects of these drugs with those of clozapine and haloperidol. METHODS: To study the effects of NRA-drugs, atypical and typical antipsychotics, we measured locomotor activity with an infra-red sensor, and stereotypy and ataxia on a rating scale. Extracellular glutamate levels were measured by in vivo microdialysis. RESULTS: NRA0045 (1 or 3 mg/kg) or clozapine (1 mg/kg) attenuated hyperlocomotion, stereotypy, and ataxia induced by PCP (7.5 mg/kg) without affecting behavior after saline injection. Although haloperidol (0.1 or 1 mg/kg) attenuated or inhibited PCP-induced behavior, this drug also affected behavior after saline injection. NRA0160 (0.1, 1, or 3 mg/kg) had no effect on behavior induced by PCP or saline. NRA0045 (3 mg/kg), but not NRA0160, inhibited PCP-induced increases in glutamate levels in the medial prefrontal cortex. PCP-induced hyperlocomotion correlated with the PCP-induced increases in glutamate levels in this brain region. CONCLUSIONS: These results suggest that the effects of NRA0045 on PCP-induced abnormal behavior are similar to those of the atypical antipsychotic clozapine. NRA0045 probably attenuates PCP-induced abnormal behavior by inhibiting the PCP-induced increase in glutamate levels in the medial prefrontal cortex; this inhibition may be mediated via the blockade of 5-HT(2A) receptors.

Adrenergic alpha-1 Receptor Antagonists↗
PubMed2005

Blockade of the mGlu5 receptor decreases basal and stress-induced cortical norepinephrine in rodents.

RATIONALE: Glutamate, the major excitatory neurotransmitter in the brain mediates its effects by both ionotropic and metabotropic receptor subtypes. Recently, the search for selective ligands for glutamate receptor subtypes has led to the discovery of 2-methyl-6-(phenylethynyl)pyridine (MPEP), an antagonist specific for metabotropic glutamate receptor 5 (mGlu5). This receptor is highly expressed in limbic forebrain regions and is thought to modulate anxiety-related processes. The noradrenergic nucleus locus coeruleus (LC) is an important mediator of stress responses and dysfunction of this system is implicated in affective disorders such as anxiety and depression. OBJECTIVES: We sought to assess the effects of mGlu5 receptor antagonists, MPEP and 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP) on cortical norepinephrine (NE) levels. METHODS: In vivo microdialysis and high-pressure liquid chromatography with electrochemical detection (HPLC-ED) were used to assess the effects of mGlu5 antagonism on extracellular NE in the frontal cortex, a major terminal field of the LC. RESULTS: Blockade of the mGlu5 receptor elicited significant reductions in extracellular NE in the frontal cortex. The benzodiazepine diazepam also reduced cortical NE. Furthermore, MPEP administration attenuated stress-induced increases in extracellular NE. CONCLUSIONS: Taken together, these data show that MPEP and MTEP, through their blockade of the mGlu5, reduce extracellular norepinephrine, the impact of which may contribute to their anxiolytic actions.

Animals↗
PubMed2005

The antinociceptive and anxiolytic-like effects of the metabotropic glutamate receptor 5 (mGluR5) antagonists, MPEP and MTEP, and the mGluR1 antagonist, LY456236, in rodents: a comparison of efficacy and side-effect profiles.

RATIONALE: Modulation of metabotropic glutamate receptor (mGluR) subtypes represents a novel approach for the treatment of neurological and psychiatric disorders. OBJECTIVES: This study was conducted to investigate the role of the mGluR5 and mGluR1 subtypes in the modulation of pain and anxiety. METHODS: The mGluR5 antagonists, 2-methyl-6-(phenylethynyl)pyridine (MPEP) and 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine (MTEP), and the mGluR1 antagonist, (4-methoxy-phenyl)-(6-methoxy-quinazolin-4-yl)-amine HCl (LY456236), were tested in models of pain [mouse formalin test, rat spinal nerve ligation (SNL)] and anxiety [Vogel conflict, conditioned lick suppression (CLS)], and their efficacious effects were compared to any associated side effects. RESULTS: The systemic administration of MPEP, MTEP, and LY456236 reduced hyperalgesia induced by formalin and mechanical allodynia following SNL. However, only LY456236 completely reversed the allodynia. In the anxiety models, MPEP (3--30 mg/kg), MTEP (3--10 mg/kg), and LY456236 (10--30 mg/kg) produced anxiolytic-like effects similar to the benzodiazepine, chlordiazepoxide (CDP, 6 mg/kg). However, only MPEP and MTEP were able to produce a level of anxiolysis comparable to CDP. In a series of tests examining potential side effects, MPEP and MTEP reduced body temperature and locomotor activity and impaired operant responding for food and rotarod performance at doses of 3--30 and 1--30 mg/kg, respectively. LY456236 reduced operant responding at 30 mg/kg. CONCLUSION: Both mGluR5 and mGluR1 antagonists are effective in models of pain and anxiety. However, an mGluR1 antagonist was more efficacious than the two mGluR5 antagonists in the pain models, which, conversely, appeared more efficacious in the anxiety models. These findings support the potential utility of mGluR5 and mGluR1 antagonists for both the treatment of chronic pain and as novel anxiolytics.

Analgesics↗
PubMed2006

Effects of group I metabotropic glutamate receptor antagonists on the behavioral sensitization to motor effects of cocaine in rats.

RATIONALE: Metabotropic glutamate receptors (mGluRs) were reported to regulate various behavioral effects of addictive drugs. OBJECTIVE: The present study evaluated the role of group I mGluRs in the progressive augmentation ("sensitization") of the behavioral effects observed after repeated, intermittent cocaine exposure. MATERIALS AND METHODS: After habituation to handling and baseline activity measurement (days 1-2), rats received eight injections of cocaine (10 mg/kg) or saline on days 3-6, 8-11, and then, were tested twice with acute saline and cocaine given in a counterbalanced manner on days 13 and 15. Before the test sessions, subjects were pretreated with mGluR1 antagonist EMQMCM (JNJ16567083, (3-ethyl-2-methyl-quinolin-6-yl)-(4-methoxy-cyclohexyl)-methanone methanesulfonate) and mGluR5 antagonist MTEP ([(2-methyl-1,3-thiazol-4-yl)ethynyl]pyridine). RESULTS: Pretreatment with EMQMCM (2.5-10 mg/kg) but not MTEP (2.5-10 mg/kg) significantly reduced expression of the sensitized ambulatory motor activity of the cocaine-experienced animals acutely challenged with cocaine. Both EMQMCM and MTEP significantly reduced vertical motor activity across all cocaine/saline treatment conditions. CONCLUSIONS: These findings indicate that the expression of behavioral sensitization to cocaine-induced stimulation of locomotor activity may be modulated by group I mGluR antagonists (mGluR1 rather than mGluR5), but these effects occur at the dose levels that attenuate vertical activity.

Analysis of Variance↗
PubMed2006

Assessing appetitive and consummatory phases of ethanol self-administration in C57BL/6J mice under operant conditions: regulation by mGlu5 receptor antagonism.

RATIONALE: The development of mouse models of ethanol consumption and ethanol-seeking behavior is of particular importance in understanding the underlying mechanisms of drug abuse because these models can enable an analysis of an effect of specific genotype on drug-seeking behavior and the interaction of potential therapeutics with genotype. However, there are some limitations with present models, notably the inability to examine appetitive and consummatory behavior separately. MATERIALS AND METHODS: In the present study, C57BL/6 mice were trained to self-administer 10% ethanol in a modified operant protocol that allowed a clear delineation of consummatory and appetitive phases. The utility of this procedure was confirmed with the use of the metabotropic glutamate 5 (mGlu5) receptor antagonist 3-[(2-methyl-1,3-thiazol-4-yl)ethynyl]-pyridine (MTEP). RESULTS: Limited-access consumption during the dark phase of the light-dark cycle with intermittent access (every second or third day) led to a high level of consumption by the mice. MTEP caused a dose-dependent decrease in both the consumption of ethanol and the appetitive response for ethanol. Furthermore, this effect was unrelated to any effect of MTEP on locomotor activity. CONCLUSIONS: The model provides a useful paradigm for examining both the appetitive and consummatory phases of ethanol consumption in mice; furthermore, the data indicate mGlu5 receptors are involved in both phases.

Alcohol Drinking↗
PubMed2000

Volatile organic compounds associated with microbial growth in automobile air conditioning systems.

Volatile organic compounds from Penicillium viridicatum and Methylobacterium mesophilicum growing on laboratory media and on component materials of automobile air conditioners were analyzed with gas chromatography and mass spectrometry. P. viridicatum produced compounds such as 4-methyl thiazole, terpenes and alcohols, whereas M. mesophilicum produced dimethyl disulfide, dimethyl trisulfide, and chlorophenol with growth on laboratory media. In comparison with laboratory media, fewer volatiles were detected from colonized foam insulation materials. Biofilms of M. mesophilicum on aluminum evaporator components produced mainly dimethyl disulfide. These biofilms, after inoculation with P. viridicatum, produced offensive smelling alcohols and esters such as 2-methyl propanol, 3-penten-2-ol, and the ethyl ester of butanoic acid. The moisture and substrates innate to the automobile air conditioning systems provided an environment suitable for microbial biofilm development and odor production. Reduction of retained moisture in the air conditioning system coupled with use of less susceptible or antimicrobial substrates are advised for remediation of the noxious odors.

Air Conditioning↗
PubMed1989

Thioacetylation method of protein sequencing: derivatization of 2-methyl-5(4H)-thiazolones for high-performance liquid chromatographic detection.

A reinvestigation of the thioacetylation method of protein sequencing (G. A. Mross and R. F. Doolittle (1971) Fed. Proc. 30, 1241. G. A. Mross and R. F. Doolittle (1977) in Advanced Methods in Protein Sequence Determination (Needleman, S. B., Ed.), pp. 1-20, Springer, Berlin) has revealed that 2-methyl-5(4H)-thiazolones, prepared by trifluoroacetic acid-catalyzed cleavage of the N-terminal amino acid from a N-thioacetylated polypeptide, were found to react instantaneously with one equivalent of carboxylic acid chloride, sulfonic acid chloride, or chloroformate to yield stable derivatives suitable for identification by high-performance liquid chromatography. NMR studies confirmed the products of the derivatization to be the corresponding 5-O-substituted-2-methylthiazoles. 2-Methyl-5(4H)-thiazolones were derivatized by reaction with 3,5-dinitrobenzoyl chloride, 4-nitrophenylchloroformate, 4-nitrobenzenesulfonyl chloride, or 4-N-dimethylaminoazobenzene-4'-sulfonyl chloride (dabsyl chloride) in dichloromethane in the presence of triethylamine. Analytical standards were prepared by 1,3-dicyclohexylcarbodiimide-catalyzed cyclization of N-thioacetyl amino acids to 2-methyl-5(4H)-thiazolones followed by derivatization with 4-nitrobenzenesulfonyl chloride. Stable crystalline 2-methyl-5-O-(4'-nitrobenzenesulfonyl)thiazole standards were obtained for 15 amino acids. Cysteine, serine, and threonine proved recalcitrant toward derivatization with 4-nitrobenzenesulfonyl chloride due to the dehydration of their respective thiazolones. Alkylated cysteine derivatives including S-beta-(4-pyridylethyl)cysteine and S-ethylcysteine were derivatized without difficulty. Cyclization of N-thioacetylproline afforded a mesoionic compound which resisted derivatization, but could be detected directly. A preliminary high-performance liquid chromatographic separation was developed and the feasibility of this approach to protein sequencing demonstrated by solid-phase degradation of the oxidized insulin B chain.(ABSTRACT TRUNCATED AT 250 WORDS)

Amino Acid Sequence↗