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Biomedical subjects

N Camerman

Publications and source records attributed to N Camerman.

At least 19 recordsLinked to original sources
PubMed2001

Two rhodamine derivatives: 9-[2-(ethoxycarbonyl)phenyl]-3,6-bis-(ethylamino)-2,7-dimethylxanthylium chloride monohydrate and 3,6-diamino-9-[2-(methoxycarbonyl)-phenyl]xanthylium chloride trihydrate.

The title compounds, C28H31N2O3(+)-Cl(-)-H2O (common name rhodamine-6g), (I), and C21H17N2O3(+)-Cl(-)-3H2O (common name rhodamine-123), (II), both have planar xanthene skeletons with a formal +1 charge on the amino N atoms delocalized through the pi-electron system so that the N-Csp(2) bond distances indicate significant double-bond character. The substituted planar phenyl groups make angles of 63.29 (8) and 87.96 (11) degrees with the xanthene planes in (I) and (II), respectively. In both molecules, the carbonyl bond vectors point toward the xanthene rings. The ethylamine groups in (I) are oriented similarly with their CH2-CH3 bond vectors pointing nearly perpendicular to the xanthene plane. The chloride ions and water molecules are disordered in both structures. In (I), the chloride ion and water molecule are disordered between two sites. One water and chloride alternately occupy the same site with occupancy factors of 0.5. The other 0.5-chloride and 0.5-water occupy two distinct positions separated by 0.747 (8) A. In (II), the chloride ion is disordered between three sites and one of the waters is disordered about two other sites. Both crystal structures are stabilized by hydrogen bonds involving the chloride ions, amino groups and water molecules, as well as by pi-pi stacking between xanthene planes.

Crystallography, X-Ray↗
PubMed2001

Crystal structure of the hydrated strontium salt of methotrexate: two independent molecules with different conformations.

The crystal and molecular structure of methotrexate has been determined by X-ray diffraction from a highly hydrated triclinic crystal form in which the asymmetric unit contains two independent methotrexate molecules with their glutamate carboxyl groups coordinated to two strontium ions. The two methotrexates exhibit differing conformations: They are almost related to one another by a pseudocenter of symmetry. This places the C(9)-N(10) bond vectors on opposite sides of the planes of the pteridine rings. The 2,4-diaminopteridines form 2-fold symmetry-related hydrogen-bonded dimers as well as hydrogen bonds to benzoyl carbonyl oxygens and lattice water molecules. This structure provides experimental proof of the existence of pteridine conformers through rotation about the C(6)-C(9) bond. Comparison of these conformers with other free and enzyme-bound methotrexate conformations shows them all to be different and illustrates the ability of the molecule to adapt to its chemical environment. The results from this crystal structure determination are experimental proof that methotrexate has not one preferred molecular conformation but may freely rotate about several bonds. They also suggest that the dihydrofolate reductase-bound methotrexate conformation is greatly influenced by the specific binding site environment of the enzyme.

Antimetabolites, Antineoplastic↗
PubMed2000

Ranitidine hydrochloride, a polymorphic crystal form.

In the title compound, dimethyl(¿5-[2-(1-methylamino-2-nitroethenylamino)ethylthiometh yl]-2- furyl¿methyl)ammonium chloride, C(13)H(23)N(4)O(3)S(+).Cl(-), protonation occurs at the dimethylamino N atom. The ranitidine molecule adopts an eclipsed conformation. Bond lengths indicate extensive electron delocalization in the N,N'-dimethyl-2-nitro-1, 1-ethenediamine system of the molecule. The nitro and methylamino groups are trans across the side chain C=C double bond, while the ethylamino and nitro groups are cis. The Cl(-) ions link molecules through hydrogen bonds.

Crystallography, X-Ray↗
PubMed2000

The antifolate trimetrexate: observation of the enzyme-binding conformation.

The crystal structure of the title compound contains four 2, 4-diamino-5-methyl-6-[(3,4,5-trimethoxyanilino)methyl]quinazoline molecules, two dimethyl sulfoxide molecules and three water molecules in the asymmetric unit, i.e. 4C(19)H(23)N(5)O(3).-2C(2)H(6)OS.3H(2)O. All four quinazoline molecules adopt trans,-gauche conformations. An extensive hydrogen-bond network involving N. N base-pairing interactions, as well as the dimethyl sulfoxide and water molecules, stabilizes the crystal structure.

Crystallography, X-Ray↗
PubMed1999

Bis(2,2-dimethylaziridinyl)phosphinic amide.

The asymmetric unit of the title compound, C8H18N3OP, contains one bis(2,2-dimethylaziridinyl)phosphinic amide molecule. The crystal structure is characterized by hydrogen bonds from the amide-N atom, which involve both H atoms of the amino group, to the phosphinic-O atom in two different molecules, thus forming infinite double-stranded chains along the base vector [100], and by hydrophobic contacts between these chains.

Antineoplastic Agents↗
PubMed1999

FF-beta-D-arabinofuranosyluracil.

In the title compound, 1-(2-deoxy-2-fluoro-beta-D-arabino-furanosyl)-5-fluoropyrimidine-2, 4(1H,3H)-dione, C9H10-F2N2O5, the furanosyl ring adopts the twisted conformation (T) with O1' endo and C1' exo. The crystal structure is characterized by a three-dimensional hydrogen-bond network involving the three H atoms bonded to heteroatoms.

Antineoplastic Agents↗
PubMed1999

A Schiff base formed from sulfanilic acid and dimethylformamide.

The crystal structure the Schiff base contains one 4-dimethylaminomethyleneaminobenzenesulfonic acid molecule in zwitterionic form [4-(dimethylaminomethyleneammonio)benzenesulfonate], and one water molecule in the asymmetric unit (C9H12N2O3S.H2O). Protonation occurs at nitrogen atom N1, but the charge is delocalized.

Crystallography, X-Ray↗
PubMed1998

(R)-(-)- and (S)-(+)-Synadenol: synthesis, absolute configuration, and enantioselectivity of antiviral effect.

Synthesis of (R)-(-)- and (S)-(+)-synadenol (1a and 2a, 95-96% ee) is described. Racemic synadenol (1a + 2a) was deaminated with adenosine deaminase to give (R)-(-)-synadenol (1a) and (S)-(+)-hypoxanthine derivative 5. Acetylation of the latter compound gave acetate 6. Reaction with N, N-dimethylchloromethyleneammonium chloride led to 6-chloropurine derivative 7. Ammonolysis furnished (S)-(+)-synadenol (2a). Absolute configuration of 1a was established by two methods: (i) synthesis from (R)-methylenecyclopropanecarboxylic acid (8) and (ii) X-ray diffraction of a single crystal of (-)-synadenol hydrochloride. Racemic methylenecyclopropanecarboxylic acid (10) was resolved by a modification of the described procedure. The R-enantiomer 8 was converted to ethyl ester 13 which was brominated to give vicinal dibromides 14. Reduction with diisobutylaluminum hydride then furnished alcohol 15 which was acetylated to the corresponding acetate 16. Alkylation-elimination procedure of adenine with 16 yielded acetates 17 and 18. Deprotection with ammonia afforded a mixture of Z- and E-isomers 1a and 19 of the R-configuration. Comparison with products 1a and 2a by chiral HPLC established the R-configuration of (-)-synadenol (1a). These results were confirmed by X-ray diffraction of a single crystal of (-)-synadenol hydrochloride. The latter forms a pseudosymmetric dimer with adenine-adenine base pairing in the lattice with the nucleobase in an anti-like conformation. Enantiomers 1a and 2a exhibit varied enantioselectivity toward different viruses. Both enantiomers are equipotent against human cytomegalovirus (HCMV) and varicella zoster virus (VZV). The S-enantiomer 2a is somewhat more effective than R-enantiomer 1a in herpes simplex virus 1 and 2 (HSV-1 and HSV-2) assays. By contrast, enantioselectivity of antiviral effect is reversed in Epstein-Barr virus (EBV) and human immunodeficiency virus type 1 (HIV-1) assays where the R-enantiomer 1a is preferred. In these assays, the S-enantiomer 2a is less effective (EBV) or devoid of activity (HIV-1).

Adenine↗
PubMed1996

Molecular structure and antioxidant specificity of purpurogallin in three types of human cardiovascular cells.

Purpurogallin (PPG) in an active cytoprotector found in certain oak barks. We have shown that PPG prolongs the survival of cultured cardiocytes from rats and rabbits against different oxidants better than do antioxidants such as Trolox (a hydrophilic analogue of vitamin E) in a morphometric assay system. First, we verified by X-ray crystallography that PPG is a bicyclic molecule comprising a phenolic ring fused with a seven-membered ring in a highly planar conformation. In analogues of PPG wherein the two double bonds in the seven membered ring of the parent molecule are saturated or where the four OH groups of the parent compound are substituted by four OCH3 groups, the derivatives are less planar and less protective of the human cells than native PPG. Second, PPG in a concentration-dependent manner protected myocytes and endothelial cells of humans against oxyradicals generated with any one of the following oxyradical generators: (a) xanthine oxidase plus hypoxanthine, (b) menadione, or (c) paraquat. In each case, PPG was more cytoprotective than comparative antioxidants. Also, PPG protected erythrocytes against peroxyl radicals better than the two PPG derivatives mentioned. Third, the cytoprotective action of PPG detected in vitro was accompanied by declines of malondialdehyde. Finally, we observed that PPG chelated ferrous ions and, therefore, can suppress the formation of radicals in the Fenton reaction. Thus, PPG with its molecular architecture and presumably its affinity for ferrous ions protects multiple types of cardiovascular cells against oxyradicals.

Animals↗
PubMed1995

Participation of acetylpseudouridine in the synthesis of a peptide bond in vitro.

Uracil, uridine, and pseudouridine were acetylated by refluxing in acetic anhydride, and the products of acetylation were incubated with a synthetic peptide (1-21) that corresponds to the N-terminal 21 amino acid residues of human myelin basic protein. Peptide bond formation, at the N alpha terminus in peptide 1-21, was obtained with acetyluracil and acetylpseudouridine, but not with acetyluridine. Transfer of an acetyl group from acetyluracil and acetylpseudouridine depended on acetylation in the N-heterocycle. X-ray crystallographic analysis definitively established N-1 as the site of acetylation in acetyluracil. Mass spectrometry of the acetylation products showed that one acetyl group was transferred to peptide 1-21, in water, by either acetyluracil or acetylpseudouridine at pH approximately 6. Release of the acetyl group by acylaminopeptidase regenerated peptide 1-21 (mass spectrometry) and automated sequencing (for five cycles) of the regenerated (deacetylated) peptide demonstrated that the N terminus was intact. The findings are discussed in the context of a possible role for pseudouridine in ribosome-catalyzed peptidyltransfer, with particular reference being made to similarities between the possible mechanism of acyl transfer by acetyluracil/pseudouridine and the mechanism of carboxyl transfer by carboxylbiotin in acetyl CoA carboxylase. The possibility that idiosyncratic appearance of a wide range of acyl substituents in myelin basic protein could be related to a peculiar involvement of ribosomal pseudouridine is mentioned.

Acetylation↗
PubMed1995

Crystal and molecular structure of paclitaxel (taxol).

Paclitaxel (formerly called taxol), an important anticancer drug, inhibits cell replication by binding to and stabilizing microtubule polymers. As drug-receptor interactions are governed by the three-dimensional stereochemistries of both participants, we have determined the crystal structure of paclitaxel to identify its conformational preferences that may be related to biological activity. The monoclinic crystals contain two independent paclitaxel molecules in the asymmetric unit plus several water and dioxane solvent molecules. Taxane ring conformation is very similar in both paclitaxel molecules and is similar to the taxane ring conformation found in the crystal structure of the paclitaxel analogue docetaxel (formerly called taxotere). The two paclitaxel molecules have carbon-13 side-chain conformations that differ from each other and from that of the corresponding side chain in the docetaxel crystal structure. The carbon-13 side-chain conformation of one paclitaxel molecule is similar to what was proposed from NMR studies done in polar solvents, while that of the other paclitaxel molecule is different and hitherto unobserved. The paclitaxel molecules interact with each other and with solvent atoms through an extensive network of hydrogen bonds. Analysis of the hydrogen-bonding network together with structure-activity studies may suggest which atoms of paclitaxel are important for binding to microtubule receptors.

Crystallography, X-Ray↗
PubMed1995

Molecular properties and myocardial salvage effects of morin hydrate.

Morin hydrate is a bioactive pigment found in yellow Brazil wood. Recently, we reported that morin hydrate prolongs the survival of three types of cells from the human circulatory system against oxyradicals generated in vitro. The protection excels that given by equimolar concentrations of ascorbate, mannitol, and Trolox. Here, we demonstrate that, in vivo, morin hydrate at 5 mumol/kg actually reduced by > 50% the tissue necrosis in post-ischemic and reperfused rabbit hearts. Mechanistically, morin hydrate not only scavenges oxyradicals, but also moderately inhibits xanthine oxidase, a free-radical generating enzyme from the ischemic endothelium. Among other possibilities, morin hydrate appears to chelate some metal ions (e.g. Fe2+) in oxyradical formation, although this needs to be examined further. Nuclear magnetic resonance (at 500 mHz) and electron-impact mass spectrometry also supported a molecular formula of C15H10O7 for morin hydrate. Only by X-ray crystallography was it clearly revealed that there are two water molecules attached by intermolecular hydrogen bonds to a morin molecule. Also, the three rings of morin hydrate approach coplanarity. This conformation favours a delocalization of electrons after oxyradical reduction, making morin an effective antioxidant. Thus, we have documented some of the molecular properties and myocardial salvage effects of morin hydrate.

Animals↗
PubMed1993

Glucosidase inhibitors: structures of deoxynojirimycin and castanospermine.

High-resolution structures of the glucosidase inhibitors deoxynojirimycin (dNM) and castanospermine (CAST) have been determined by X-ray diffraction. The crystal parameters are a = 10.751(3) and 8.788(3) A, b = 9.263(3) and 8.172(3) A, c = 7.719(2) and 6.507(2) A, and space group P2(1)2(1)2(1) and P2(1) for dNM and CAST, respectively. (beta = 105.44(8) degrees for CAST.) The absolute configuration of CAST has also been established. Stereochemical comparisons with natural glucosidase substrates such as maltose and methyl glucoside show great similarities in the positioning of functional groups, and indicate the basis for enzyme inhibition. Conformational comparison between dNM and CAST suggests the greater activity of CAST may be due to the fixed axial positioning of the O6 atom; the results have implications for the design of analogues for potential anti-HIV and other antiviral therapies.

1-Deoxynojirimycin↗
PubMed1991

L-alanyl-L-alanyl-L-alanine: parallel pleated sheet arrangement in unhydrated crystal structure, and comparisons with the antiparallel sheet structure.

The tripeptide L-alanyl-L-alanyl-L-alanine has been crystallized from a water/dimethylformamide solution in an unhydrated form, with cell dimensions a = 11.849, b = 10.004, c = 9.862 A, beta = 101.30 degrees, monoclinic space group P21 with 4 molecules per cell (2 independent molecules in the asymmetric unit). The structure was determined by direct methods and refined to a discrepancy index R = 0.057. The tri-L-alanine molecules are packed in a parallel pleated sheet arrangement with unusually long amide nitrogen-carbonyl oxygen contacts within sheets. Comparisons are made with the antiparallel pleated sheet structure of tri-L-alanine hemihydrate, previously crystallized from the same solvent system.

Amino Acid Sequence↗
PubMed1990

Structure of the anti-human immunodeficiency virus agent 3'-fluoro-3'-deoxythymidine and electronic charge calculations for 3'-deoxythymidines.

The crystal and molecular structures of the anti-human immunodeficiency virus agent 3'-fluoro-3'-deoxythymidine have been determined by x-ray diffraction and stereochemical comparisons with thymidine have been made. Atomic charge distributions have been calculated by the complete neglect of differential overlap method for thymidine and antiretrovirally active and inactive C3'-substituted analogues. The structural and electronic results suggest that antiviral activity in these analogues may be correlated with the presence of an electronegative atom attached to C3'.

Antiviral Agents↗
PubMed1989

Tryptophanyl-tRNA synthetase from Bacillus subtilis. Characterization and role of hydrophobicity in substrate recognition.

The tryptophanyl-tRNA synthetase from Bacillus subtilis was purified to homogeneity and characterized. It has an alpha 2 subunit structure and a molecular weight of 77,000. Tryptophanyl-tRNA synthetase does not catalyze any significant proofreading. It activates tryptophan as well as the three fluorinated analogues, DL-4-fluoro-, DL-5-fluoro-, or DL-6-fluorotryptophan (4F-, 5F-, and 6F-Trp), in the ATP-pyrophosphate exchange reaction. In the aminoacylation reaction, the fluorotryptophans act as competitive inhibitors of Trp. Their relative activities follow the same order in both reactions: Trp greater than 4F-Trp greater than 6F-Trp greater than 5F-Trp. This order is the inverse of the order of relative hydrophobicities of these compounds, pointing to the importance of hydrophobic interactions in the selective recognition by tryptophanyl-tRNA synthetase among this group of substrates. To define the physical basis of the relative hydrophobicities, the crystallographic structure of 4F-Trp was determined and compared to that of trptophan. Charge distributions calculated for tryptophan and its different fluoroanalogues on the basis of molecular structures were supported by their carbon-13 NMR spectra. Correlations between charge distributions and relative hydrophobicities suggest that the polarity of the C-F bond represents an underlying factor determining the hydrophobicities of 4F-, 5F-, and 6F-Trp, thus relating tryptophanyl-tRNA synthetase selectivity toward tryptophan and its fluoroanalogues directly to their electronic configurations.

Adenosine Monophosphate↗
PubMed1989

Crystallographic resolution and crystal and molecular structures of stereoisomers of 1,3,5-triglycidyl-s-triazinetrione.

The crystal and molecular structures of alpha and beta isomers of the antineoplastic alkylating agent 1,3,5-triglycidyl-s-triazinetrione (TGT) have been determined by X-ray diffraction. Although the isomers differ chemically only in the order of a carbon and an oxygen atom in one of the glycidyl epoxide rings, the molecular conformations and crystal packing arrangements are very different. The different physical and biological properties of the two stereoisomers can be explained on the basis of the structures. The sample of alpha-TGT was found to be a mixture of alpha and beta forms, and it is suggested that use of pure alpha-TGT may lead to better therapeutic results.

Chemical Phenomena↗