Virgil Simplaceanu - Academia.edu (original) (raw)
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Papers by Virgil Simplaceanu
Federation Proceedings, May 29, 1987
Journal of Alzheimers Disease, 2010
Amyloid-β peptide (Aβ) oligomerization has a profound role in Alzheimer's disease pathophysiology... more Amyloid-β peptide (Aβ) oligomerization has a profound role in Alzheimer's disease pathophysiology. Biophysical studies have shown that smaller sized inhaled anesthetics promote oligomerization by inducing perturbation of three critical amino acid residues (G29, A30, and I31) located in the helix-loop-helix domain of Aβ. In this present experimental study, using state-of-the-art nuclear magnetic resonance, we have monitored the influence of a larger sized intravenous anesthetic, diazepam, as well as diazepam co-administered with halothane, on Aβ. It was concluded that diazepam (in isolation) does not interact with the G29, A30, and I31 residues, and no Aβ oligomerization occurs in the presence of 0.101 mM diazepam, even after 63 days. However, when diazepam was co-administered with halothane, profound Aβ oligomerization is observed. These results strengthen the hypothesis that the presence of smaller molecular sized anesthetic is instrumental in promoting Aβ oligomerization even when co-administered with a larger sized anesthetic, namely diazepam.
Proceedings of the National Academy of Sciences, 2003
Many important proteins perform their physiological functions under allosteric control, whereby t... more Many important proteins perform their physiological functions under allosteric control, whereby the binding of a ligand at a specific site influences the binding affinity at a different site. Allosteric regulation usually involves a switch in protein conformation upon ligand binding. The energies of the corresponding structures are comparable, and, therefore, the possibility that a structure determined by x-ray diffraction in the crystalline state is influenced by its intermolecular contacts, and thus differs from the solution structure, cannot be excluded. Here, we demonstrate that the quaternary structure of tetrameric human normal adult carbonmonoxy-hemoglobin can readily be determined in solution at near-physiological conditions of pH, ionic strength, and temperature by NMR measurement of 15 N- 1 H residual dipolar couplings in weakly oriented samples. The structure is found to be a dynamic intermediate between two previously solved crystal structures, known as the R and R2 stat...
Glycobiology, 1998
The polysaccharide chains of enterobacterial common antigen (ECA) consist of linear trisaccharide... more The polysaccharide chains of enterobacterial common antigen (ECA) consist of linear trisaccharide repeat units with the structure →3)-α-D-Fuc4NAc-(1→4)-β-D-ManNAcA-(1→ 4)-α-D-GlcNAc-(1→, where Fuc4NAc is 4-acetamido-4,6-dideoxy-D-galactose, ManNAcA is N-acetyl-D-mannosaminuronic acid, and GlcNAc is N-acetyl-D-glucosamine. The major form of ECA (ECA PG) consists of polysaccharide chains that are believed to be covalently linked to diacylglycerol through phosphodiester linkage; the phospholipid moiety functions to anchor molecules in the outer membrane. The ECA trisaccharide repeat unit is assembled as a polyisoprenyl-linked intermediate which has been tentatively identified as Fuc4NAc-ManNAcA-GlcNAc-pyrophosphorylundecaprenol (lipid III). Subsequent chain-elongation presumably occurs by a blockpolymerization mechanism. However, the identity of the polyisoprenoid carrier-lipid has not been established. Accordingly, the current studies were conducted in an effort to structurally characterize the polyisoprenyl lipid-carrier involved in ECA synthesis. Isolation and characterization of the lipid carrier was facilitated by the accumulation of a ManNA-cA-GlcNAc-pyrophosphorylpolyisoprenyl lipid (lipid II) in mutants of Salmonella typhimurium defective in the synthesis of TDP-Fuc4NAc, the donor of Fuc4NAc residues for ECA synthesis. Analyses of lipid II preparations by fast atom bombardment tandem mass spectroscopy (FAB-MS/MS) resulted in the identification of the lipid-carrier as the 55-carbon polyisoprenyl alcohol, undecaprenol. These analyses also resulted in the identification of a novel glycolipid which copurified with lipid II. FAB-MS/MS analyses of this glycolipid revealed its structure to be 1,2-diacyl-sn-glycero-3-pryophosphoryl-GlcNAc-ManNAcA (DGP-disaccharide). An examination of purified ECA PG by phosphorus-31 nuclear magnetic resonance spectroscopy confirmed that the polysaccharide chains are linked to diacylglycerol through phosphodiester linkage. Thus, DGP-disaccharide does not appear to be an intermediate in ECA PG synthesis. Nevertheless, although the available evidence clearly indicate that lipid II is a precursor of DGPdisaccharide, the function of this novel glycolipid is not yet known, and it may be an intermediate in the biosynthesis of a molecule other than ECA PG .
Revue Roumaine de Physique, 1978
Archiv fur Geschwulstforschung, 1973
The temperature dependences of the spin-spin and spin-lattice relaxation times of H in ZrH/sub 1.... more The temperature dependences of the spin-spin and spin-lattice relaxation times of H in ZrH/sub 1.65/ and ZrH/sub 1.75/ were found in the temperature range 80--300 /sup 0/K. (AIP)
Journal of molecular biology, 1984
Fluorine-19 nuclear magnetic resonance has been used to investigate the histidine-binding protein... more Fluorine-19 nuclear magnetic resonance has been used to investigate the histidine-binding protein J from Salmonella typhimurium. The protein has been labeled with fluorine-19 by growing the bacterial cells of a tryptophan auxotroph in the presence of 5-fluorotryptophan. Incorporation of up to 70% was achieved. The binding of L-histidine to the 19F-labeled protein is not affected by the isotopic labeling. The protein contains one tryptophan residue, giving rise to a single 19F resonance. Upon binding L-histidine to 19F-labeled histidine-binding protein J, the observed 19F resonance is shifted downfield by about 0.6 parts per million, indicating a conformational change of the protein molecule and a more hydrophobic environment for the 19F nucleus. Additional fluorescence experiments confirm that the tryptophan residue is located inside the hydrophobic core of the protein. 19F spin-lattice relaxation times of the 19F-labeled protein as a function of temperature show no difference betwe...
BACKGROUND Little data exist wherein both the 31P nuclear magnetic resonance (NMR) signals and bi... more BACKGROUND Little data exist wherein both the 31P nuclear magnetic resonance (NMR) signals and biochemical changes associated with hepatic regeneration after a 70% hepatic resection have been assessed simultaneously. EXPERIMENTAL DESIGN Two groups of rats were used: one group underwent a 70% partial hepatectomy and the second underwent a sham operation. Both groups were followed sequentially for 192 hours by in vivo serial 31P-NMR spectroscopy of the liver and its phospholipid extracts. Liver injury and function were assessed by biochemical means. RESULTS After surgery, a significant reduction in ATP and an increase in the phosphomonoester signal for the hepatectomized animals were noted as compared with the controls (p < 0.05). The phosphodiester content of the liver in the hepatectomized rats declined to nonmeasurable amounts in vivo. The nadir of ATP occurred 72 hours after surgery. The area of the phosphomonoester relative to an external reference of methylenediphosphonic aci...
Journal of Hepatology, 1989
Drugs and the Liver: High Risk Patients and Transplantation, 1993
Cyclosporin A (CsA) is a drug that has allowed the field of human organ transplantation to develo... more Cyclosporin A (CsA) is a drug that has allowed the field of human organ transplantation to develop from an experimental stage to a practical and effective form of therapy (1). FK 506, a novel compound, is now becoming of interest as an alternative immunosuppressive agent (2, 3), and preliminary reports have appeared to demonstrate its usefulness in organ transplantation (4).
Journal of biomolecular NMR, 2004
Pulsed proton nuclear magnetic resonance was used to differentiate between normal and malignant t... more Pulsed proton nuclear magnetic resonance was used to differentiate between normal and malignant tissues.
Archiv für Geschwulstforschung
Federation Proceedings, May 29, 1987
Journal of Alzheimers Disease, 2010
Amyloid-β peptide (Aβ) oligomerization has a profound role in Alzheimer's disease pathophysiology... more Amyloid-β peptide (Aβ) oligomerization has a profound role in Alzheimer's disease pathophysiology. Biophysical studies have shown that smaller sized inhaled anesthetics promote oligomerization by inducing perturbation of three critical amino acid residues (G29, A30, and I31) located in the helix-loop-helix domain of Aβ. In this present experimental study, using state-of-the-art nuclear magnetic resonance, we have monitored the influence of a larger sized intravenous anesthetic, diazepam, as well as diazepam co-administered with halothane, on Aβ. It was concluded that diazepam (in isolation) does not interact with the G29, A30, and I31 residues, and no Aβ oligomerization occurs in the presence of 0.101 mM diazepam, even after 63 days. However, when diazepam was co-administered with halothane, profound Aβ oligomerization is observed. These results strengthen the hypothesis that the presence of smaller molecular sized anesthetic is instrumental in promoting Aβ oligomerization even when co-administered with a larger sized anesthetic, namely diazepam.
Proceedings of the National Academy of Sciences, 2003
Many important proteins perform their physiological functions under allosteric control, whereby t... more Many important proteins perform their physiological functions under allosteric control, whereby the binding of a ligand at a specific site influences the binding affinity at a different site. Allosteric regulation usually involves a switch in protein conformation upon ligand binding. The energies of the corresponding structures are comparable, and, therefore, the possibility that a structure determined by x-ray diffraction in the crystalline state is influenced by its intermolecular contacts, and thus differs from the solution structure, cannot be excluded. Here, we demonstrate that the quaternary structure of tetrameric human normal adult carbonmonoxy-hemoglobin can readily be determined in solution at near-physiological conditions of pH, ionic strength, and temperature by NMR measurement of 15 N- 1 H residual dipolar couplings in weakly oriented samples. The structure is found to be a dynamic intermediate between two previously solved crystal structures, known as the R and R2 stat...
Glycobiology, 1998
The polysaccharide chains of enterobacterial common antigen (ECA) consist of linear trisaccharide... more The polysaccharide chains of enterobacterial common antigen (ECA) consist of linear trisaccharide repeat units with the structure →3)-α-D-Fuc4NAc-(1→4)-β-D-ManNAcA-(1→ 4)-α-D-GlcNAc-(1→, where Fuc4NAc is 4-acetamido-4,6-dideoxy-D-galactose, ManNAcA is N-acetyl-D-mannosaminuronic acid, and GlcNAc is N-acetyl-D-glucosamine. The major form of ECA (ECA PG) consists of polysaccharide chains that are believed to be covalently linked to diacylglycerol through phosphodiester linkage; the phospholipid moiety functions to anchor molecules in the outer membrane. The ECA trisaccharide repeat unit is assembled as a polyisoprenyl-linked intermediate which has been tentatively identified as Fuc4NAc-ManNAcA-GlcNAc-pyrophosphorylundecaprenol (lipid III). Subsequent chain-elongation presumably occurs by a blockpolymerization mechanism. However, the identity of the polyisoprenoid carrier-lipid has not been established. Accordingly, the current studies were conducted in an effort to structurally characterize the polyisoprenyl lipid-carrier involved in ECA synthesis. Isolation and characterization of the lipid carrier was facilitated by the accumulation of a ManNA-cA-GlcNAc-pyrophosphorylpolyisoprenyl lipid (lipid II) in mutants of Salmonella typhimurium defective in the synthesis of TDP-Fuc4NAc, the donor of Fuc4NAc residues for ECA synthesis. Analyses of lipid II preparations by fast atom bombardment tandem mass spectroscopy (FAB-MS/MS) resulted in the identification of the lipid-carrier as the 55-carbon polyisoprenyl alcohol, undecaprenol. These analyses also resulted in the identification of a novel glycolipid which copurified with lipid II. FAB-MS/MS analyses of this glycolipid revealed its structure to be 1,2-diacyl-sn-glycero-3-pryophosphoryl-GlcNAc-ManNAcA (DGP-disaccharide). An examination of purified ECA PG by phosphorus-31 nuclear magnetic resonance spectroscopy confirmed that the polysaccharide chains are linked to diacylglycerol through phosphodiester linkage. Thus, DGP-disaccharide does not appear to be an intermediate in ECA PG synthesis. Nevertheless, although the available evidence clearly indicate that lipid II is a precursor of DGPdisaccharide, the function of this novel glycolipid is not yet known, and it may be an intermediate in the biosynthesis of a molecule other than ECA PG .
Revue Roumaine de Physique, 1978
Archiv fur Geschwulstforschung, 1973
The temperature dependences of the spin-spin and spin-lattice relaxation times of H in ZrH/sub 1.... more The temperature dependences of the spin-spin and spin-lattice relaxation times of H in ZrH/sub 1.65/ and ZrH/sub 1.75/ were found in the temperature range 80--300 /sup 0/K. (AIP)
Journal of molecular biology, 1984
Fluorine-19 nuclear magnetic resonance has been used to investigate the histidine-binding protein... more Fluorine-19 nuclear magnetic resonance has been used to investigate the histidine-binding protein J from Salmonella typhimurium. The protein has been labeled with fluorine-19 by growing the bacterial cells of a tryptophan auxotroph in the presence of 5-fluorotryptophan. Incorporation of up to 70% was achieved. The binding of L-histidine to the 19F-labeled protein is not affected by the isotopic labeling. The protein contains one tryptophan residue, giving rise to a single 19F resonance. Upon binding L-histidine to 19F-labeled histidine-binding protein J, the observed 19F resonance is shifted downfield by about 0.6 parts per million, indicating a conformational change of the protein molecule and a more hydrophobic environment for the 19F nucleus. Additional fluorescence experiments confirm that the tryptophan residue is located inside the hydrophobic core of the protein. 19F spin-lattice relaxation times of the 19F-labeled protein as a function of temperature show no difference betwe...
BACKGROUND Little data exist wherein both the 31P nuclear magnetic resonance (NMR) signals and bi... more BACKGROUND Little data exist wherein both the 31P nuclear magnetic resonance (NMR) signals and biochemical changes associated with hepatic regeneration after a 70% hepatic resection have been assessed simultaneously. EXPERIMENTAL DESIGN Two groups of rats were used: one group underwent a 70% partial hepatectomy and the second underwent a sham operation. Both groups were followed sequentially for 192 hours by in vivo serial 31P-NMR spectroscopy of the liver and its phospholipid extracts. Liver injury and function were assessed by biochemical means. RESULTS After surgery, a significant reduction in ATP and an increase in the phosphomonoester signal for the hepatectomized animals were noted as compared with the controls (p < 0.05). The phosphodiester content of the liver in the hepatectomized rats declined to nonmeasurable amounts in vivo. The nadir of ATP occurred 72 hours after surgery. The area of the phosphomonoester relative to an external reference of methylenediphosphonic aci...
Journal of Hepatology, 1989
Drugs and the Liver: High Risk Patients and Transplantation, 1993
Cyclosporin A (CsA) is a drug that has allowed the field of human organ transplantation to develo... more Cyclosporin A (CsA) is a drug that has allowed the field of human organ transplantation to develop from an experimental stage to a practical and effective form of therapy (1). FK 506, a novel compound, is now becoming of interest as an alternative immunosuppressive agent (2, 3), and preliminary reports have appeared to demonstrate its usefulness in organ transplantation (4).
Journal of biomolecular NMR, 2004
Pulsed proton nuclear magnetic resonance was used to differentiate between normal and malignant t... more Pulsed proton nuclear magnetic resonance was used to differentiate between normal and malignant tissues.
Archiv für Geschwulstforschung