Search

Your search keyword '"Bulaj, Grzegorz"' showing total 463 results
Start Over Author "Bulaj, Grzegorz"
463 results on '"Bulaj, Grzegorz"'

52. The novel anticonvulsant neuropeptide and galanin analogue, NAX-5055, does not alter energy and amino acid metabolism in cultured brain cells

Author

Aldana, Blanca I, Waagepetersen, Helle S, Schousboe, Arne, White, H Steve, Bulaj, Grzegorz, Walls, Anne B, Aldana, Blanca I, Waagepetersen, Helle S, Schousboe, Arne, White, H Steve, Bulaj, Grzegorz, and Walls, Anne B

Abstract

A large body of evidence suggests that the neuropeptide galanin plays an important role in seizure control. In line with this, it was demonstrated that the galanin analogue, NAX-5055, exerts a potent anticonvulsant activity in animal seizure models. We recently found that the NAX-5055-mediated anticonvulsant action involves modulation of both excitatory and inhibitory neurotransmission. Since homeostasis of neurotransmitters and cerebral energy metabolism are intimately linked, it was investigated whether the effects of NAX-5055 on neurotransmission involve changes in energy metabolism and in particular glucose- and amino acid metabolism. With this aim, cultured neurons from mouse brain were incubated with [U-(13) C]glucose in absence or presence of NAX-5055. Since effects of NAX-5055 on neurotransmission were detected during repetitive stimulation, we tested potential metabolic effects while mimicking repetitive bursts of neurotransmitter release as occurring in the intact brain. The metabolic pathways were mapped using gas-chromatography coupled to mass-spectrometry. We found that NAX-5055 does not modify glucose metabolism in glutamatergic and GABAergic neurons. Furthermore, the effect of NAX-5055 on astrocyte-neuron metabolic interactions was investigated by incubating co-cultures of astrocytes and either glutamatergic or GABAergic neurons with [U-(13) C]glucose or the glial-selective substrate [1,2-(13) C]acetate, with or without NAX-5055. In the presence of NAX-5055, no changes in the metabolic landscape were traced. The findings suggest that the anticonvulsant action of NAX-5055 and the accompanying changes in neurotransmission do not involve alterations in energy and amino acid metabolism. Hence, NAX-5055 appears to be an anti-seizure drug candidate displaying no unwanted side effects concerning brain energy and amino acid homeostasis. © 2017 Wiley Periodicals, Inc.

Published
2017

53. Circular logic: nonribosomal peptide-like macrocyclization with a ribosomal peptide catalyst

Author

McIntosh, John A., Robertson, Charles R., Agarwal, Vinayak, Nair, Satish K., Bulaj, Grzegorz W., and Schmidt, Eric W.

Subjects
Peptides -- Structure, Peptides -- Chemical properties, Polyketides -- Chemical properties, Proteases -- Structure, Proteases -- Chemical properties, Ribosomes -- Structure, Ribosomes -- Chemical properties, Thioesters -- Chemical properties, Chemistry
Abstract

A protease from ribosomal peptide biosynthesis with the ability to macrocyclize diverse substrates, including those resembling nonribosomal peptide and hybrid polyketide-peptide products is reported. The proposed mechanism is equivalent to thioesterase-catalyzed chemistry, but the substrates are amide bonds rather than thioesters.

Published
2010

54. [mu]-Conotoxin KIIIA derivatives with divergent affinities versus efficacies in blocking voltage-gated sodium channels

Author

Min-Min Zhang, Han, Tiffany S., Olivera, Baldomero M., Bulaj, Grzegorz, and Yoshikami, Doju

Subjects
Bacterial toxins -- Structure, Bacterial toxins -- Chemical properties, Gene mutations -- Analysis, Ligand binding (Biochemistry) -- Analysis, Sodium channels -- Research, Xenopus -- Physiological aspects, Xenopus -- Genetic aspects, Biological sciences, Chemistry
Abstract

Various replacements of residue 7 are examined to determine whether affinity and efficacy of pore-blocking ligands of sodium channels are inexorably linked. The ability to manipulate a [mu]-conopeptideEs affinity and efficacy, as well as its capacity to interfere with subsequent tetrodotoxin bonding, has expanded its scope as a reagent for probing sodium channel structure and function, leading to the development of [mu]-conotoxin KIIIA derivatives as safe analgesics.

Published
2010

55. Site-specific effects of diselenide bridges on the oxidative folding of a cystine knot peptide, [omega]-selenoconotoxin GVIA

Author

Gowd, Konkallu Hanumae, Yarotskyy, Viktor, Elmslie, Keith S., Skalicky, Jack J., Olivera, Baldomero M., and Bulaj, Grzegorz

Subjects
Glutathione -- Chemical properties, Oxidation-reduction reaction -- Analysis, Peptides -- Structure, Peptides -- Chemical properties, Protein folding -- Analysis, Biological sciences, Chemistry
Abstract

Several structural, as well as functional studies are conducted to explain the impact of the site-specific incorporation of diselenide bridges on the oxidative folding of a cystine knot peptide. The discussed folding process is shown to be extremely beneficial in the synthesis of a diverse group of disulfide-rich peptides.

Published
2010

56. Conantokin-Br from Conus brettinghami and selectivity determinants for the NR2D subunit of the NMDA receptor

Author

Twede, Vernon D., Teichert, Russell W., Walker, Craig S., Gruszczynski, Pawe, Kazmierkiewicz, Rajmund, Bulaj, Grzegorz, and Olivera, Baldomero M.

Subjects
Cone snails -- Physiological aspects, Cone snails -- Genetic aspects, Glutamate -- Chemical properties, Substitution reactions -- Analysis, Biological sciences, Chemistry
Abstract

The characterization of a 24 AA conantokin from Conus brettinghami, the first conantokin that does not have the conserved glutamate residue at position 2 is reported. The results revealed that systematic definition of key determinants in the conantokin peptides for NMDA receptor subtype selectivity is an essential component in the development of conantokin peptides that are highly selective for each specific NMDA receptor subtype.

Published
2009

57. Structure of the analgesic [mu]-conotoxin KIIIA and effects on the structure and function of disulfide deletion

Author

Khoo, Keith K., Zhi-Ping Feng, Smith, Brian J., Min-Min Zhang, Yoshikami, Doju, Olivera, Baldomero M., Bulaj, Grzegorz, and Norton, Raymond S.

Subjects
Cone snails -- Physiological aspects, Cysteine -- Chemical properties, Nuclear magnetic resonance spectroscopy -- Usage, Peptides -- Chemical properties, Sodium channels -- Analysis, Biological sciences, Chemistry
Abstract

NMR spectroscopy is used to determine the solution structure of [mu]-conotoxin KIIIA, from Conus kinoshitai which blocks mammalian neuronal voltage-gated sodium channels (VGSCs) and is a potent analgesic following systemic administration in mice. The results showed that the key residues for VGSC binding lie mostly on an [alpha]-helix and that the removal of the Cys1-Cys9 disulfide have minimum effect on the structure and function of the peptide and hence could be applied for development and design of [mu]-conotoxin mimetics.

Published
2009

58. NMR-based mapping of disulfide bridges in cysteine-rich peptides: application to the [mu]-conotoxin SxIIIA

Author

Walewska, Aleksandra, Skalicky, Jack J., Davis, Darrell R., Min-Min Zhang, Lopez-Vera, Estuardo, Watkins, Maren, Han, Tiffany S., Yoshikami, Doju, Olivera, Baldomero M., and Bulaj, Grzegorz

Subjects
Cysteine -- Chemical properties, Nuclear magnetic resonance spectroscopy -- Usage, Organosulfur compounds -- Chemical properties, Organosulfur compounds -- Structure, Peptides -- Chemical properties, Chemistry
Abstract

A new approach is described that is employed for an efficient NMR-based mapping of the disulfide bridges in cysteine-rich peptides. The application of the method to the three-disulfide-bridged conotoxin, [mu]-conotoxin SxIIIA is shown to be extremely effective and efficient.

Published
2008

59. Structure, dynamics, and selectivity of the sodium channel blocker [mu]-conotoxin SIIIA

Author

Shenggen Yao, Min-Min Zhang, Yoshikami, Doju, Azam, Layla, Olivera, Baldomero M., Bulaj, Grzegorz, and Norton, Raymond S.

Subjects
Cone snails -- Composition, Nuclear magnetic resonance -- Usage, Sodium channels -- Research, Biological sciences, Chemistry
Abstract

The structure of [mu]-conotoxin SIIIA from Conus stratus is studied with the help of nuclear magnetic resonance. [mu]-SIIIA is an irreversible blocker of sodium channels at submicromolar levels.

Published
2008

60. Role of hydroxypyrolines in the in vitro oxidative folding and biological activity of conotoxins

Author

Lopez-Vera, Estuardo, Walewska, Aleksandra, Skalicky, Jack J., Olivera, Baldomero M., and Bulaj, Grzegorz

Subjects
Hydroxylation -- Research, Hydroxyproline -- Chemical properties, Oxidation-reduction reaction -- Analysis, Protein folding -- Research, Biological sciences, Chemistry
Abstract

The importance of hydroxypyrolines (Hyp) in the in vitro oxidative folding and biological activity of conotoxins is discussed. The results suggest that proline hydroxylation is very important in the structure and function of all the proteins and peptides.

Published
2008

61. Structure and sodium channel activity of an excitatory [I.sub.1]-superfamily conotoxin

Author

Buczek, Olga, Olivera, Baldomero M., Bulaj, Grzegorz, Norton, Raymond S., Fiedler, Brian, Ping Chen, Yoshikami, Doju, Wei, Daxiu, Babon, Jeffrey J., and Xiaodong Yang

Subjects
Nuclear magnetic resonance spectroscopy -- Usage, Sodium compounds -- Structure, Sodium compounds -- Spectra, Biological sciences, Chemistry
Abstract

NMR spectroscopy is used for studying the structure and sodium channel activity of an excitatory [I.sub.1]-superfamily conotoxin. There is a convergence of structure and function in [iota]-RXIA, as its disulfide pairing and structure has resembled those of funnel web spider toxins, which have targeted sodium channels.

Published
2007

62. Novel conotoxins from Conus striatus and Conus kinoshitai selectivity block TTX-resistant sodium channels

Author

Bulaj, Grzegorz, West, Peter J., Garrett James E., Marsh, Maren, Min-Min Zhang, Norton, Raymond S., Smith, Brian J., Yoshikami, Doju, and Olivera, Baldomero M.

Subjects
Tetrodotoxin -- Research, Snails -- Research, Biological sciences, Chemistry
Abstract

The characterization of two novel Mu-conotoxins from the venoms of two different fish-hunting species, Conus striatus and Conus kinoshitai is reported. Structural and functional differences among Mu-conotoxins SmIIIA, SIIIA, and KIIIA offer a unique insight into the evolutionary engineering of conotoxin activity.

Published
2005

67. Propeptide does not act as an intramolecular chaperone but facilitates protein disulfide isomerase-assisted folding of a conotoxin precursor

Author

Buczek, Olga, Olivera, Baldomero M., and Bulaj, Grzegorz

Subjects
Thermodynamics -- Research, Amino acid sequence -- Research, Oxidation-reduction reaction -- Research, Biological sciences, Chemistry
Abstract

The oxidative folding of a conotoxin precursor, pro-GI, pertaining to the alpha-conotoxin family is studied to find out whether the propeptide potentially functions as an intramolecular chaperone. Results reveal that propeptide sequence did not directly help to folding kinetics and thermo dynamics and the propeptide region of pro-GI plays a significant role when oxidative folding is catalyzed by protein disulfide isomerase.

Published
2004

68. Circular Logic: Nonribosomal Peptide-like Macrocyclization with a Ribosomal Peptide Catalyst

Author

McIntosh, John A., Robertson, Charles R., Agarwal, Vinayak, Nair, Satish K., Bulaj, Grzegorz W., and Schmidt, Eric W.

Abstract

A protease from ribosomal peptide biosynthesis macrocyclizes diverse substrates, including those resembling nonribosomal peptide and hybrid polyketide−peptide products. The proposed mechanism is analogous to thioesterase-catalyzed chemistry, but the substrates are amide bonds rather than thioesters.

Published
2024
Full Text
View/download PDF

72. Conantokins Derived from the Asprella Clade Impart ConRl-B, an NMDA Receptor Antagonist with a Unique Selectivity Profile for NR2B Subunits

Author

Gowd, Konkallu Hanumae, Han, Tiffany S., Twede, Vernon, Gajewiak, Joanna, Smith, Misty D., Watkins, Maren, Platt, Randall J., Toledo, Gabriela, White, H. Steve, Olivera, Baldomero M., and Bulaj, Grzegorz

Subjects
Epilepsy, Genome, Protein Conformation, Conus Snail, DNA, Receptors, N-Methyl-D-Aspartate, Article, Mice, nervous system, Gene Expression Regulation, Animals, Anticonvulsants, Amino Acid Sequence, Cloning, Molecular, Conotoxins, Peptides
Abstract

Using molecular phylogeny has accelerated the discovery of peptidic ligands targeted to ion channels and receptors. One clade of venomous cone snails, Asprella, appears to be significantly enriched in conantokins, antagonists of N-methyl d-aspartate receptors (NMDARs). Here, we describe the characterization of two novel conantokins from Conus rolani, including conantokin conRl-B that has shown an unprecedented selectivity for blocking NMDARs that contain NR2B subunits. ConRl-B shares only some sequence similarity with the most studied NR2B selective conantokin, conG. The divergence between conRl-B and conG in the second inter-Gla loop was used to design analogues for structure-activity studies; the presence of Pro10 was found to be key to the high potency of conRl-B for NR2B, whereas the ε-amino group of Lys8 contributed to discrimination in blocking NR2B- and NR2A-containing NMDARs. In contrast to previous findings for Tyr5 substitutions in other conantokins, conRl-B[L5Y] showed potencies on the four NR2 NMDA receptor subtypes that were similar to those of the native conRl-B. When delivered into the brain, conRl-B was active in suppressing seizures in the model of epilepsy in mice, consistent with NR2B-containing NMDA receptors being potential targets for antiepileptic drugs. Circular dichroism experiments confirmed that the helical conformation of conRl-B is stabilized by divalent metal ions. Given the clinical applications of NMDA antagonists, conRl-B provides a potentially important pharmacological tool for understanding the differential roles of NMDA receptor subtypes in the nervous system. This work shows the effectiveness of coupling molecular phylogeny, chemical synthesis, and pharmacology for discovering new bioactive natural products.

Published
2012

75. A marine analgesic peptide, Contulakin-G, and neurotensin are distinct agonists for neurotensin receptors: uncovering structural determinants of desensitization properties

Author

Lee, Hee-Kyoung, primary, Zhang, Liuyin, additional, Smith, Misty D., additional, Walewska, Aleksandra, additional, Vellore, Nadeem A., additional, Baron, Riccardo, additional, McIntosh, J. Michael, additional, White, H. Steve, additional, Olivera, Baldomero M., additional, and Bulaj, Grzegorz, additional

Published
2015
Full Text
View/download PDF

76. Neuroprotective and cardioprotective conopeptides: An emerging class of drug leads

Author

Twede, Vernon D, Miljanich, George, Olivera, Baldomero M, and Bulaj, Grzegorz

Subjects
animal structures, Cardiovascular Agents, Calcium Channel Blockers, complex mixtures, Receptors, N-Methyl-D-Aspartate, Article, omega-Conotoxins, Structure-Activity Relationship, Neuroprotective Agents, Drug Discovery, Potassium Channel Blockers, Animals, Humans, Conotoxins, Excitatory Amino Acid Antagonists, Sodium Channel Blockers
Abstract

The peptides in the venoms of predatory marine snails belonging to the genus Conus ('cone snails') have well-established therapeutic applications for the treatment of pain and epilepsy. This review discusses the neuroprotective and cardioprotective potential of four families of Conus peptides (conopeptides), including omega-conotoxins that target voltage-gated Ca2+ channels, conantokins that target NMDA receptors, mu-conotoxins that target voltage-gated Na+ channels, and kappa- and kappaM-conotoxins that target K+ channels. The diversity of Conus peptides that have already been shown to exhibit neuroprotective/cardioprotective activity suggests that marine snail venoms are a potentially rich source of drug leads with diverse mechanisms.

Published
2009

79. Ribosomally synthesized and post-translationally modified peptide natural products : overview and recommendations for a universal nomenclature

Author

Arnison, Paul G., Bibb, Mervyn J., Bierbaum, Gabriele, Bowers, Albert A., Bugni, Tim S., Bulaj, Grzegorz, Camarero, Julio A., Campopiano, Dominic J., Challis, Gregory L., Clardy, Jon, Cotter, Paul D., Craik, David J., Dawson, Michael, Dittmann, Elke, Donadio, Stefano, Dorrestein, Pieter C., Entian, Karl-Dieter, Fischbach, Michael A., Garavelli, John S., Göransson, Ulf, Gruber, Christian W., Haft, Daniel H., Hemscheidt, Thomas K., Hertweck, Christian, Hill, Colin, Horswill, Alexander R., Jaspars, Marcel, Kelly, Wendy L., Klinman, Judith P., Kuipers, Oscar P., Link, A. James, Liu, Wen, Marahiel, Mohamed A., Mitchell, Douglas A., Moll, Gert N., Moore, Bradley S., Mueller, Rolf, Nair, Satish K., Nes, Ingolf F., Norris, Gillian E., Olivera, Baldomero M., Onaka, Hiroyasu, Patchett, Mark L., Piel, Joern, Reaney, Martin J. T., Rebuffat, Sylvie, Ross, R. Paul, Sahl, Hans-Georg, Schmidt, Eric W., Selsted, Michael E., Severinov, Konstantin, Shen, Ben, Sivonen, Kaarina, Smith, Leif, Stein, Torsten, Suessmuth, Roderich D., Tagg, John R., Tang, Gong-Li, Truman, Andrew W., Vederas, John C., Walsh, Christopher T., Walton, Jonathan D., Wenzel, Silke C., Willey, Joanne M., van der Donk, Wilfred A., Arnison, Paul G., Bibb, Mervyn J., Bierbaum, Gabriele, Bowers, Albert A., Bugni, Tim S., Bulaj, Grzegorz, Camarero, Julio A., Campopiano, Dominic J., Challis, Gregory L., Clardy, Jon, Cotter, Paul D., Craik, David J., Dawson, Michael, Dittmann, Elke, Donadio, Stefano, Dorrestein, Pieter C., Entian, Karl-Dieter, Fischbach, Michael A., Garavelli, John S., Göransson, Ulf, Gruber, Christian W., Haft, Daniel H., Hemscheidt, Thomas K., Hertweck, Christian, Hill, Colin, Horswill, Alexander R., Jaspars, Marcel, Kelly, Wendy L., Klinman, Judith P., Kuipers, Oscar P., Link, A. James, Liu, Wen, Marahiel, Mohamed A., Mitchell, Douglas A., Moll, Gert N., Moore, Bradley S., Mueller, Rolf, Nair, Satish K., Nes, Ingolf F., Norris, Gillian E., Olivera, Baldomero M., Onaka, Hiroyasu, Patchett, Mark L., Piel, Joern, Reaney, Martin J. T., Rebuffat, Sylvie, Ross, R. Paul, Sahl, Hans-Georg, Schmidt, Eric W., Selsted, Michael E., Severinov, Konstantin, Shen, Ben, Sivonen, Kaarina, Smith, Leif, Stein, Torsten, Suessmuth, Roderich D., Tagg, John R., Tang, Gong-Li, Truman, Andrew W., Vederas, John C., Walsh, Christopher T., Walton, Jonathan D., Wenzel, Silke C., Willey, Joanne M., and van der Donk, Wilfred A.

Abstract

This review presents recommended nomenclature for the biosynthesis of ribosomally synthesized and post-translationally modified peptides (RiPPs), a rapidly growing class of natural products. The current knowledge regarding the biosynthesis of the >20 distinct compound classes is also reviewed, and commonalities are discussed.

Published
2013
Full Text
View/download PDF

84. Ribosomally synthesized and post-translationally modified peptide natural products: overview and recommendations for a universal nomenclature

Author

Arnison, Paul G., primary, Bibb, Mervyn J., additional, Bierbaum, Gabriele, additional, Bowers, Albert A., additional, Bugni, Tim S., additional, Bulaj, Grzegorz, additional, Camarero, Julio A., additional, Campopiano, Dominic J., additional, Challis, Gregory L., additional, Clardy, Jon, additional, Cotter, Paul D., additional, Craik, David J., additional, Dawson, Michael, additional, Dittmann, Elke, additional, Donadio, Stefano, additional, Dorrestein, Pieter C., additional, Entian, Karl-Dieter, additional, Fischbach, Michael A., additional, Garavelli, John S., additional, Göransson, Ulf, additional, Gruber, Christian W., additional, Haft, Daniel H., additional, Hemscheidt, Thomas K., additional, Hertweck, Christian, additional, Hill, Colin, additional, Horswill, Alexander R., additional, Jaspars, Marcel, additional, Kelly, Wendy L., additional, Klinman, Judith P., additional, Kuipers, Oscar P., additional, Link, A. James, additional, Liu, Wen, additional, Marahiel, Mohamed A., additional, Mitchell, Douglas A., additional, Moll, Gert N., additional, Moore, Bradley S., additional, Müller, Rolf, additional, Nair, Satish K., additional, Nes, Ingolf F., additional, Norris, Gillian E., additional, Olivera, Baldomero M., additional, Onaka, Hiroyasu, additional, Patchett, Mark L., additional, Piel, Joern, additional, Reaney, Martin J. T., additional, Rebuffat, Sylvie, additional, Ross, R. Paul, additional, Sahl, Hans-Georg, additional, Schmidt, Eric W., additional, Selsted, Michael E., additional, Severinov, Konstantin, additional, Shen, Ben, additional, Sivonen, Kaarina, additional, Smith, Leif, additional, Stein, Torsten, additional, Süssmuth, Roderich D., additional, Tagg, John R., additional, Tang, Gong-Li, additional, Truman, Andrew W., additional, Vederas, John C., additional, Walsh, Christopher T., additional, Walton, Jonathan D., additional, Wenzel, Silke C., additional, Willey, Joanne M., additional, and van der Donk, Wilfred A., additional

Published
2013
Full Text
View/download PDF

87. Patient-Empowerment Interactive Technologies

Author

Bruggers, Carol S., primary, Altizer, Roger A., additional, Kessler, Robert R., additional, Caldwell, Craig B., additional, Coppersmith, Kurt, additional, Warner, Laura, additional, Davies, Brandon, additional, Paterson, Wade, additional, Wilcken, Jordan, additional, D’Ambrosio, Troy A., additional, German, Massiell L., additional, Hanson, Glen R., additional, Gershan, Lynn A., additional, Korenberg, Julie R., additional, and Bulaj, Grzegorz, additional

Published
2012
Full Text
View/download PDF

90. Conantokins Derived from the Asprella Clade Impart conRl-B, an N-Methyl d-Aspartate Receptor Antagonist with a Unique Selectivity Profile for NR2B Subunits

Author

Gowd, Konkallu Hanumae, primary, Han, Tiffany S., additional, Twede, Vernon, additional, Gajewiak, Joanna, additional, Smith, Misty D., additional, Watkins, Maren, additional, Platt, Randall J., additional, Toledo, Gabriela, additional, White, H. Steve, additional, Olivera, Baldomero M., additional, and Bulaj, Grzegorz, additional

Published
2012
Full Text
View/download PDF

Catalog

Books, media, physical & digital resources
See catalog results