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Biomedical subjects

B L Currie

Publications and source records attributed to B L Currie.

At least 19 recordsLinked to original sources
PubMed1992

Evaluation of some substrates and potential inhibitors of tissue pyroglutamyl aminopeptidase I.

A fluorometric enzyme assay was developed to evaluate the ability of a variety of compounds to bind to and/or inhibit pyroglutamyl aminopeptidase I. Among these compounds were a series of chloromethyl ketone analogues of thyrotropin releasing hormone (TRH) which had previously been shown to possess TRH-like activity in the central nervous system and have now been found to be good inhibitors of pyroglutamyl aminopeptidase. Thus, it is suggested that the observed TRH-like CNS activity could derive indirectly from inhibition of endogenous TRH degradation by pyroglutamyl aminopeptidase I.

Amino Acid Sequence↗
PubMed1992

Structure modification and biological activity of some griseofulvin derivatives.

Griseofulvin is an orally acting anti-fungal antibiotic with very limited water solubility. Five chemical modifications were made on the griseofulvin structure in order to evaluate these changes on the antifungal and water solubility properties. Antifungal activity was measured against Tricophyton mentagrophytes, T. rubrum, T. terrestre, and Microsporum canis. The oxime of griseofulvin was the most potent of the five compounds tested, but it was only of equal or less potency than griseofulvin. The somewhat increased water solubility of some of these compounds was offset by the lower anti-fungal potency of the structural modification.

Fungi↗
PubMed1990

Hemoglobin S antigelation agents based on 5-bromotryptophan with potential for sickle cell anemia.

5-Bromotryptophan (5-BrTrp) is the most potent amino acid derivative reported in the literature to inhibit the gelation of hemoglobin S (from sickle cell anemia patients). Trp-Trp is also more potent than Trp as an antigelation agent. Therefore, we have prepared a series of dipeptides containing 5-BrTrp and evaluated the antigelation activity. 5-BrTrp-5-BrTrp is the most potent, i.e., 5.9 times the activity of Trp, followed by 5-BrTrp-Trp and then Trp-5-BrTrp. This improved antigelation potency for 5-BrTrp-5-BrTrp and 5-BrTrp-Trp is very significant and will be pursued further as lead compounds with potential for sickle cell anemia.

Anemia, Sickle Cell↗
PubMed1986

Interaction of a spin-labeled phenylalanine analogue with normal and sickle hemoglobins: detection of site-specific interactions through spin-label-induced 1H NMR relaxation.

In a preliminary report, we have previously shown that N-[(2,2,5,5-tetramethyl-1-oxypyrrolidin-3-yl)carbonyl]-L-phenyl ala nine tert-butyl ester (SL-Phe) exhibits specific binding to hemoglobin and an antiaggregation activity more than 2 orders of magnitude greater than that of phenylalanine [Lu, H.-Z., Currie, B. L., & Johnson, M. E. (1984) FEBS Lett. 173, 259-263]. Transverse 1H NMR relaxation measurements have been used to investigate the interaction of SL-Phe with hemoglobin molecules by use of the resonances assigned to the C2 protons of the beta 2 His, the beta 143 His, and the beta 146 or beta 97 His residues as intrinsic probes. Distance calculations using the paramagnetically induced relaxation data suggest that the SL-Phe binding site is approximately 12-16 A away from the C2 protons of the beta 2 His and the beta 146 or beta 97 His residues in the (carbonmonoxy)hemoglobin tetramer; for deoxyhemoglobin, the distances are approximately 14-17 A between the SL-Phe binding site and the C2 protons of the beta 2 His, the beta 143 His, and the beta 146 His residues. Calculations using the (carbonmonoxy)hemoglobin crystal atomic coordinates only restrict the probable SL-Phe binding region to the full F and H helices of the beta-chain and a small section of the alpha-chain. For deoxyhemoglobin, the distance calculations provide greater restrictions on the probable binding region, limiting it to small sections of the beta-chain F, G, and H helices near the EF bend and to a few residues on the alpha-chain.(ABSTRACT TRUNCATED AT 250 WORDS)

Affinity Labels↗
PubMed1985

Quantitative determination of tolazoline in serum and urine.

A high-performance liquid chromatographic procedure is described for the analysis of tolazoline in serum and urine. This assay procedure is suitable for the analysis of micro-samples (50 or 100 microliters serum and 100 microliters urine). Samples are extracted in a single step and injected into a reversed-phase high-performance liquid chromatography system for detection at 210 nm. The clinical applicability of this assay is demonstrated by the determination of tolazoline serum and urine concentrations in neonates. In addition, the presence of urine conjugates and the extent of serum protein binding were investigated. This assay procedure has the required sensitivity (0.1 microgram/ml), accuracy and precision for both routine monitoring and pharmacokinetic characterization of tolazoline in neonates and adults.

Chromatography, High Pressure Liquid↗
PubMed1984

Binding of a spin-labeled phenylalanine analog to sickle hemoglobin: EPR and NMR studies.

We have synthesized a spin-label analog of phenylalanine as a competitive inhibitor probe of the sickle hemoglobin aggregation process. Sickle hemoglobin gelation measurements indicate that the spin-label phenylalanine analog is a potent inhibitor of deoxy sickle hemoglobin aggregation. We have also used spin label EPR and high-resolution proton NMR to study the interaction of the phenylalanine analog with hemoglobin, and find that the kinetic off-rate is comparable to, or slower than the hemoglobin rotational rate (i.e., greater than or equal to 10(8) s-1), and that at least one, and perhaps two significant localized interaction region(s) exist within a few angstroms of the beta chain N- and C-termini. Correlation with other known structural information suggests that the observed interaction sites may be relevant to the mechanism for inhibition of sickle hemoglobin aggregation.

Binding Sites↗
PubMed1982

Potential thyroliberin affinity labels II: Chloroacetyl substituted phenylalanyl prolineamides.

Three analogs of thyroliberin (I) were prepared. These compounds, N-m-chloroacetylbenzoyl-phenylalanyl-prolineamide (VIa), N-p-chloroacetylbenzoyl-phenylalanyl-prolineamide (VIb) and N-chloroacetyl-alanyl-phenylalanyl-prolineamide (IX), were designed as potential I antagonist affinity labels. However, no significant antagonist activity was observed. Compounds VIa and IX were found to have weak agonist activity. Cyclo (Phe-Pro) an analog of the I metabolite, cyclo (His-Pro), was found, however, to have significant I antagonist activity, but no agonist activity.

Affinity Labels↗
PubMed1982

A comparison of resolution-enhancement methods in saturation-transfer EPR. 15N isotopically substituted spin labels and 35 GHz high-frequency operation.

The use of (15)N isotopic substitution and 35 GHz (Q-band) operation as resolution enhancement methods in saturation-transfer electron paramagnetic resonance (ST-EPR) are compared. We find that both methods offer roughly comparable enhancements in ST-EPR resolution. The most powerful approach to resolving complex ST-EPR spectral behavior, however, will probably be the combined use of multiple-frequency X- and Q-band operation with (15)N isotopically substituted spin labels.

Electron Spin Resonance Spectroscopy↗
PubMed1981

Potential thyroliberin affinity labels. 1. Chloroacetyl-substituted phenylalanylpyrrolidines.

Six analogues of thyroliberin (TRH) that have a chloroacetyl substituent at the amino terminus have been prepared as potential affinity labels for the TRH receptor. These compounds are N-(chloroacetyl)-L-alanyl-L-phenylalanylpyrrolidine (ClAc-Ala-Phe-Pyrr; 14), N-[m-(chloroacetyl)benzoyl]-L-phenylalanylpyrrolidine (m-ClAcBz-Phe-Pyrr; 11a), N-[m-(chloroacetyl)benzoyl]-L-alanyl-L-phenylalanylpyrrolidine (m-ClAcBz-Ala-Phe-Pyrr; 15a), N-[p-(chloroacetyl)benzoyl]-L-phenylalanylpyrrolidine (p-ClAcBz-Phe-Pyrr; 11b), and N-[p-(chloroacetyl)benzoyl]-L-alanyl-L-phenylalanylpyrrolidine (p-ClAcBz-Ala-Phe-Pyrr; 15b). Pyroglutamyl-L-phenylalanylpyrrolidine was also synthesized as a model agonist. Weak agonist activity was observed for 11a, 11b, and 15b. These three analogues do not contain the amide group of the pyroglutamyl moiety that was previously thought to be essential for intrinsic activity. No significant antagonist activity was observed for these compounds at the doses tested.

Affinity Labels↗
PubMed1979

Lack of evidence for thyrotropin-releasing hormone deamidation in normal and hyperthyroid human sera.

Two-hour incubations of human serum with 50 ng TRH or pyroglutamyl-histidyl-proline (TRH-OH) were performed under substrate conditions of 0.2 microgram substrate/ml serum. During incubations with normal serum, 46.3 +/- 1.3 (SEM) ng TRH were degraded while only 14.2 +/- 5.1 ng TRH-OH were degraded (P less than 0.001). During incubations with serum from patients with hyperthyroidism, 42.7 +/- 2.6 ng TRH were degraded compared to only 19.6 +/- 2.0 ng TRH-OH (P less than 0.001). Despite the fact that TRH degradation was significantly greater than TRH-OH degradation in both normal and hyperthyroid serum, no formation of TRH-OH (less than 3.1 ng/incubation tube) from TRH was detected. Formation of TRH-OH from TRH was also not noted when normal or hyperthyroid serum was incubated with TRH at substrate concentrations of 62.5 microgram/ml serum. These data confirm other reports that TRH deamidation does not occur in normal serum and extends this observation to hyperthyroid serum.

Humans↗
PubMed1977

High-pressure liquid chromatography of peptides.

Peptides varying in size from di- to decapeptide have been subjected to high-pressure liquid chromatography on Phenyl-Corasil, Poragel PN, and Poragel PS under reversed-phase conditions with acetonitrile-water mixtures. It has been found that residual silanol groups in the Phenyl-Corasil and the functional groups in the Poragels significantly influence retention. Peptides were also chromatographed on a Hydrogel IV gel filtration packing with aqueous eluants, and it was found that effects other than gel filtration play a major role in determining retention.

Chromatography, Gel↗