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Biomedical subjects

N Berova

Publications and source records attributed to N Berova.

At least 37 records · Page 2Linked to original sources
PubMed1997

Configuration of heptopyranoside and heptofuranoside side chains: 2-anthroate, a powerful chromophore for exciton coupled CD.

The absolute configuration of the acyclic side chain of heptopyranosides and heptofuranosides was determined by exciton coupled CD, employing the strongly fluorescent 2-anthroate chromophore. The usage of this chromophore offers significant improvements over previous chemical and spectroscopic procedures since its intense fluorescence greatly facilitates the isolation and HPLC purification at the nanogram scale. The large amplitudes of the bisignate spectra allow CD manipulations in the 1 x 10(-7) M range.

Anthracenes↗
PubMed1997

Theoretical calculation of circular dichroic exciton-split spectra in presence of three interacting 2-naphthoate chromophores.

Ample experimental evidence shows that the principle of pairwise additivity holds in exciton coupled CD systems consisting of three or more interacting chromophores. This principle is one of the most important from a practical viewpoint. However, the rule has so far not been proven theoretically. In order to prove the additivity principle by calculation, three ouabagenin bisnaphthoates and 1,3,19-tris-naphthoates were chosen as models. Since this represents a challenging case where the 2-naphthoate chromophore can adopt s-cis or s-trans conformations and, moreover the C-19 side chain of ouabagenin is flexible, Monte Carlo conformational search was performed prior to the CD calculation. The pi-electron SCF-CI-DV MO calculation of CD was applied to all conformers within 3 kcal/mol range from the lowest energy. Good agreement between experimental and theoretical CD spectra was obtained for the ouabagenin bisnaphthoates and trisnaphthoate.

Carboxylic Acids↗
PubMed1996

Picomole scale stereochemical analysis of sphingosines and dihydrosphingosines.

We have developed a simple picomole (low nanogram) scale HPLC scheme which can separate all eight isomers of sphingosine and dihydrosphingosine thus leading to the identification of their relative and absolute configurations. The amino group of the sample is derivatized to its fluorescent N-naphthimide which is analyzed by normal and chiral phase HPLC, coupled with fluorescence peak detection. If necessary, the results of this HPLC method can be further corroborated by measurements of circular dichroic (CD) spectra of the N-naphthimido-derivatives and/or N,O-chromophoric derivatives.

Chromatography, High Pressure Liquid↗
PubMed1996

Exciton coupled circular dichroic studies of self-assembled brevetoxin-porphyrin conjugates in lipid bilayers and polar solvents.

BACKGROUND: Brevetoxins, involved in the 'red tide' as well as shellfish poisoning, are known to bind to cell membranes and membrane proteins. Brevetoxin B (BTX-B) interacts specifically with neuronal sodium channels. We recently found that BTX also induces selective ion movements across lipid bilayers through transmembrane BTX self-assemblies. RESULTS: We examined the self-assembly of several BTX derivatives in the presence and absence of cations and lipid bilayers using the powerful porphyrin chromophores as circular dichroism labels. BTX derivatives self-assemble into tubes, which can bind to metals both when soluble and when inserted into the bilayer to form transmembrane pores. Depending on the tendency of the BTX derivative to self-aggregate (the critical 'micelle' concentration, cmc), it may aggregate in solution before membrane insertion, or may insert itself into the membrane as a monomer before assembling the pore. CONCLUSIONS: The active BTX-B complex in lipid bilayers is a cyclic, transmembrane self-assembly consisting of antiparallel aligned BTX molecules that can mediate selective ion movement through membranes. The differences in pore formation mechanisms between BTX derivatives may be reflected in differences in pore formation by natural BTX variants, perhaps explaining their varying levels of toxicity.

Circular Dichroism↗
PubMed1996

Intramolecular porphyrin pi,pi-stacking: absolute configurational assignment of acyclic compounds with single chiral centers by exciton coupled circular dichroism.

We report a new concept based on exciton coupled circular dichroism (CD) for assigning absolute configurations to a single chiral center *CXYSL, where X is -OH or -NH2, Y is an acyclic chain with terminal OH or -NH2, and S (small) and L (large) represent sterically distinct groups. It consists of a one step attachment of porphyrins to X and Y followed by CD measurement. The key event is intramolecular porphyrin pi,pi-stacking, which converts the flexible, acyclic substrate into a rigid stacked conformation characterized by bisignate exciton split CD curves. Since the stacked conformer is sterically controlled by the two groups, S and L, the sign of the exciton split CD is directly governed by the spatial arrangement of these groups. This approach is applicable to various acyclic compounds with different C/C distances (1,3 approximately 1,15) between the functional groups, but not to 1,2-C/C.

Acids, Acyclic↗
PubMed1995

Na,K-ATPase inhibitors from bovine hypothalamus and human plasma are different from ouabain: nanogram scale CD structural analysis.

The specific, high affinity binding of plant-derived digitalis glycosides by the mammalian sodium and potassium transporting adenosine triphosphatase (Na,K-ATPase, or sodium pump), a plasma membrane enzyme with critical physiological importance in mammalian tissues, has raised the possibility that a mammalian analog of digitalis might exist. We previously isolated and structurally characterized from bovine hypothalamus a novel isomer of the plant glycoside, ouabain, which differs structurally only in the attachment site and/or the stereochemistry of the steroid moiety [Tymiak et al. (1993) Proc. Natl. Acad. Sci. U.S.A. 90, 8189-8193]. Hamlyn and co-workers reported a molecule purified from human plasma which by mass spectrometry could not be distinguished from plant ouabain [Hamlyn et al. (1991) Proc. Natl. Acad. Sci. U.S.A. 88, 6259-6263]. Since rhamnoside cardiotonic steroids are not known as natural products from mammalian sources, it became important to compare these two pure isolates to determine if the same or structurally distinct compounds has been found. Our results indicate that the human and bovine Na,K-ATPase-inhibitors are identical, but different from plant ouabain. This supports the notion that the human sodium pump may be under specific physiological regulation by a mammalian analog of the digitalis glycosides.

Animals↗
PubMed1995

A new approach in exciton-coupled circular dichroism (ECCD)--insertion of an auxiliary stereogenic center.

There are cases in which exciton coupling between two chromophores does not occur because the two electric transition moments which should interact are coplanar. This is seen with cyclohexane-1,4-diols (both ee or ea) and a wide variety of 3-hydroxy carotenoids, 3-hydroxyretinoids, etc. A general approach to deal with such cases is to acylate one of the hydroxyl groups with a chiral allenic acid substituted with a suitable chromophore, e.g., CHROM-CH = C = CH-COOH. The allenic bond introduces a 90 degrees twist at the italicized central carbon so that the allenic CHROM now couples with the second chromophore. This concept of introducing an auxiliary allenic center should be of general applicability in other similar cases.

Alkadienes↗
PubMed1995

Combined synthetic/CD strategy for the preparation and configurational assignments of model acyclic 1,3-polyols with a 1,2-diol terminal.

Acyclic 1,3-polyols or skipped polyols are widely distributed in nature. Particularly skipped 1,3-polyols with a terminal 1,2-diol group are present in numerous antifungal polyene macrolides in various masked forms. Although over 200 polyene macrolides are known, the planar structures of only about 40 have been determined, while those for which the full stereochemistry has been elucidated is less than ten. No simple method exists for configurational assignments of the 1,3-polyols moieties; moreover, this class of compounds are difficult to crystallize. In order to develop a general chiroptical method for structure determination of acyclic 1,3-polyols, we have combined a divergent synthetic approach with CD to prepare all possible stereoisomers of 1,2,4-triols, 1,2,4,6-tetrols and 1,2,4,6,8-pentols. The current set of reference polyols should be useful for setting up reference CD libraries and for model studies leading to a general method for configurational assignment of acyclic polyols. This strategy can be used to synthesize further extended members of acyclic 1,3-polyols and mixed 1,2/1,3-polyols which can be used for structural investigations of polyene macrolides and related compounds.

Circular Dichroism↗
PubMed1995

Structural studies of vinblastine alkaloids by exciton coupled circular dichroism.

SCF-CI-dipole velocity MO calculations have shown that the bisignate circular dichroic curves of vinblastine/vincristine alkaloids at ca 210 and 220-230 nm are due to exciton coupling between the indoline and indole moieties. Furthermore, a combination of X-ray crystal structure data with MM2 local energy minimization provides a convenient means for estimation of the preferred solution conformation.

Circular Dichroism↗
PubMed1994

Malonofungin: an antifungal aminomalonic acid from Phaeoramularia fusimaculans.

In screening for antifungal metabolites, a novel compound, malonofungin, exhibiting growth inhibitory activity against Botrytis cinerea (grey mould), has been isolated from fermentations of Phaeoramularia fusimaculans CBS 616.87. Its structure is established as (E)-(3R,4S,5S)-5-acetoxy-2-amino-2-carboxy-3,4-dihydroxy-14-oxoicos++ +-6-enoic acid, representing an addition to the rare class of naturally occurring aminomalonic acids. 1H NMR data and extensive use of CD spectroscopy have been utilized to establish the absolute stereochemistry of malonofungin. The structural and biological relationship of malonofungin to previously reported fungal metabolites is discussed.

Acetylation↗
PubMed1994

Binding of ketoprofen to human serum albumin studied by circular dichroism.

The protein binding of ketoprofen has been studied using circular dichroism titration method as well as the new algorithm proposed by the authors for the treatment of data obtained. The quantitative parameters association constants (k) and number of binding sites (N) have been determined. It is proved that the protein binding of Ketoprofen is going through separate stages and the number of binding sites probably arises. It is acceptable that a high affinity binding takes place primarily (kI = 3.8 x 10(6) l.mol-1). Later, due to the conformational changes in the protein molecule the binding areas are modified and the number of binding sites considerably arises (NI = 3.5 and NII = 14), while the binding affinity reduces 100-fold (kII = 5.10(4) l.mol-1). The number of binding sites has been studied and an identification of the chromophore taking part in the drug-protein interaction has been performed on the base of UV- and CD spectra. A mechanism of the interaction is proposed which coincides with the stepwise binding model.

Circular Dichroism↗
PubMed1993

Physicochemical characterization of a ouabain isomer isolated from bovine hypothalamus.

Recent reports have shown the presence of a ouabain-like inhibitor of Na+/K(+)-ATPase in humans. We have purified a bovine hypothalamic Na+/K(+)-ATPase inhibitory factor (HIF) by using affinity chromatography combined with HPLC. This inhibitor has a molecular weight of 584 as determined by ion-spray mass spectrometry, making it isobaric with ouabain. Glycosidase treatment or acid hydrolysis of HIF released only L-rhamnose, the hexose isomer found in ouabain, as detected by chiral GC/MS. Additionally, enzymatically generated desrhamnosyl HIF was found to have a molecular weight of 438, as does ouabagenin, the aglycone of ouabain. HIF and its aglycone were indistinguishable from ouabain and ouabagenin, respectively, by reversed-phase HPLC retention times. However, derivatization with naphthoylimidazole followed by HPLC revealed different retention times for naphthoylation products of HIF and ouabain. Subsequent CD spectroscopy on isolated naphthoylation products of HIF and ouabain confirmed that they were different. This study provides chromatographic and spectroscopic evidence that ouabain and HIF are isomeric cardenolides. The structural difference is presumed to account for the significant differences in biological properties observed for HIF and ouabain.

Animals↗
PubMed1993

Oligosaccharide microscale analysis by circular dichroic spectroscopy: reference spectra for chromophoric D-fructofuranoside derivatives.

The microscale analytical method that is being developed in this group for the structure determination of oligosaccharides yields monosaccharide derivatives bearing two types of chromophores suitable for exciton-coupling, namely, 4-bromobenzoate (lambda max 245 nm) and 4-methoxycinnamate (lambda max 311 nm). Comparison of the circular dichroic (CD) curves of these subunits to those in the reference library allows for the determination of the sugar identities, linkage positions, and the absolute configurations. The 32 possible derivatives of methyl alpha- and beta-D-fructofuranosides bearing four chromophores were prepared and their CD spectra recorded. These data serve to extend the CD library, which already encompasses pyranoside derivatives with the gluco-, galacto-, and manno-configurations, and extend the utility of this methodology to the analysis of fructose-containing oligosaccharides.

Bromobenzoates↗
PubMed1990

[Synthesis, stereochemistry and anticonvulsant action of 4-phenyltetrahydroisoquinolines].

The racemic and optically active 4'- and 8-substituted tetrahydroisoquinolines 2-5 have been synthesized and their effect on the water-immersion stress ulcer in rats has been studied. All compounds prevent the formation of stress ulcer, the strongest effect being exhibited by compound 4 and its dextrarotatory isomer (R1 = Cl, R2 = NHCOOC2H5). The antiulcer activity of 4 is 30 to 50 times higher than that of the H2 receptor antagonists Cimetidin and Ranitidin used for comparison. The absolute configuration of the optically active compounds 2, 3 and 4 has been determined by means of chemical correlation. The antiulcer activity of 4 is characterized by enantioselectivity, S-(+)-4 is three times as active than R-(-)-4.

Animals↗