Search results for: Chanoch Kronman

Items from 1 to 19 out of 19 results

article

Identifying exposures to ribosome-inactivating proteins in blood samples: amplification of ricin-induced ribosomal damage products enables sensitive detection of active toxin and circulating depurinated 28S rRNA

Reut Falach, Ofir Israeli, Yoav Gal, Anita Sapoznikov, more

Forensic Toxicology > 2018 > 36 > 2 > 375-384

Purpose Ricin, a highly potent plant-derived toxin, operates by site-specific depurination of ribosomes, which in turn leads to protein synthesis arrest. Recently, we presented the TRISOL [Truncated RNA Identification by Synthetic Oligonucleotide Ligation] method for the highly sensitive detection of exposures to type II ribosome-inactivating proteins such as ricin in clinical samples, based on the...

article

Determination of ricin intoxication in biological samples by monitoring depurinated 28S rRNA in a unique reverse transcription-ligase-polymerase chain reaction assay

Ofir Israeli, Reut Falach, Anita Sapoznikov, Yoav Gal, more

Forensic Toxicology > 2018 > 36 > 1 > 72-80

Purpose Type II ribosome inactivating proteins (RIPs II) such as ricin, exert their cytotoxic effect by depurinating a specific adenosine within the 28S rRNA, which in turn leads to inhibition of protein synthesis and cell death. Therapeutic intervention in case of exposure to RIP II toxins, requires the development of a specific and sensitive method for the detection of the active toxin in biological...

article

Extended therapeutic window for post-exposure treatment of ricin intoxication conferred by the use of high-affinity antibodies

Tal Noy-Porat, Ron Alcalay, Eyal Epstein, Tamar Sabo, more

Toxicon > 2017 > 127 > C > 100-105

The plant toxin ricin is considered a potential bioterror agent against which there is no available antidote. To date, neutralizing antibodies are the most promising post-exposure treatment for ricin intoxication, yet so far they were shown to be effective only when given within several hours post exposure. As part of an ongoing effort to develop efficient ricin-countermeasures, we tested whether...

article

Quantitative profiling of the in vivo enzymatic activity of ricin reveals disparate depurination of different pulmonary cell types

Reut Falach, Anita Sapoznikov, Yoav Gal, Ofir Israeli, more

Toxicology Letters > 2016 > 258 > C > 11-19

The plant-derived toxins ricin and abrin, operate by site-specific depurination of ribosomes, which in turn leads to protein synthesis arrest. The clinical manifestation following pulmonary exposure to these toxins is that of a severe lung inflammation and respiratory insufficiency. Deciphering the pathways mediating between the catalytic activity and the developing lung inflammation, requires a quantitative...

article

Antibody treatment against pulmonary exposure to abrin confers significantly higher levels of protection than treatment against ricin intoxication

Tamar Sabo, Yoav Gal, Eitan Elhanany, Anita Sapoznikov, more

Toxicology Letters > 2015 > 237 > 2 > 72-78

Abrin, a potent plant-derived toxin bearing strong resemblance to ricin, irreversibly inactivates ribosomes by site-specific depurination, thereby precipitating cessation of protein synthesis in cells. Due to its high availability and ease of preparation, abrin is considered a biological threat, especially in context of bioterror warfare. To date, there is no established therapeutic countermeasure...

article

Rapid assessment of antibody-induced ricin neutralization by employing a novel functional cell-based assay

Yoav Gal, Ron Alcalay, Tamar Sabo, Tal Noy-Porat, more

Journal of Immunological Methods > 2015 > 424 > C > 136-139

Ricin is one of the most potent and lethal toxins known against which there is no available antidote. Currently, the most promising countermeasures against the toxin are based on neutralizing antibodies elicited by active vaccination or administered passively. A cell-based assay is widely applied for the primary screening and evaluation of anti-ricin antibodies, yet such assays are usually time-consuming...

article

Antibody/doxycycline combined therapy for pulmonary ricinosis: Attenuation of inflammation improves survival of ricin-intoxicated mice

Yoav Gal, Ohad Mazor, Ron Alcalay, Nehama Seliger, more

Toxicology Reports > 2014 > 1 > C > 496-504

Ricin, a highly toxic plant-derived toxin, is considered a potential weapon in biological warfare due to its high availability and ease of preparation. Pulmonary exposure to ricin results in the generation of an acute edematous inflammation followed by respiratory insufficiency and death. Passive immunization with polyclonal anti-ricin antibodies conferred protection against pulmonary ricinosis, however,...

article

Next generation OP-bioscavengers: A circulatory long-lived 4-PEG hypolysine mutant of F338A-HuAChE with optimal pharmacokinetics and pseudo-catalytic characteristics

Chanoch Kronman, Ofer Cohen, Ohad Mazor, Arie Ordentlich, more

Chemico-Biological Interactions > 2010 > 187 > 1-3 > 253-258

We have shown previously that conjugation of polyethylene glycol (PEG) chains to recombinant human acetylcholinesterase (rHuAChE) results in the extension of its residence time in the circulation of mice and monkeys [1,2]. By profiling the pharmacokinetic behavior of an array of well-defined hypolysine human mutant AChE molecules following PEGylation, we now determine that the duration of these enzyme...

article

Flexibility versus “rigidity” of the functional architecture of AChE active center

Avigdor Shafferman, Dov Barak, Dana Stein, Chanoch Kronman, more

Chemico-Biological Interactions > 2008 > 175 > 1-3 > 166-172

Functional architecture of the AChE active center appears to be characterized by both structural “rigidity”, necessary to stabilize the catalytic triad as well as by flexibility in accommodating the different, high affinity AChE ligands. These seemingly conflicting structural properties of the active center are demonstrated through combination of structural methods with kinetic studies of the enzyme...

article

Polyethylene-glycol conjugated recombinant human acetylcholinesterase serves as an efficacious bioscavenger against soman intoxication

Chanoch Kronman, Ofer Cohen, Lily Raveh, Ohad Mazor, more

Toxicology > 2007 > 233 > 1-3 > 40-46

Extensive pharmacokinetic studies in both mice and rhesus macaques, with biochemically well defined forms of native and recombinant AChEs from bovine, rhesus and human origin, allowed us to determine an hierarchical pattern by which post-translation-related factors and specific amino-acid epitopes govern the pharmacokinetic performance of the enzyme molecule. In parallel, we demonstrated that controlled...

article

Lessons from functional analysis of AChE covalent and noncovalent inhibitors for design of AD therapeutic agents

Dov Barak, Arie Ordentlich, Dana Kaplan, Chanoch Kronman, more

Chemico-Biological Interactions > 2005 > 157-158 > Complete > 219-226

Determination of the 3D-structure of acetylcholinesterase (AChE) of Torpedo californica over a decade ago, and more recently that of human enzyme together with extensive targeted mutagenesis of the mammalian AChEs led to a fine mapping of the multiple functional domains within the active center of the enzyme. Many of the contributions of this active center architecture to accommodation of noncovalent...

article

Functional requirements for the optimal catalytic configuration of the AChE active center

Avigdor Shafferman, Dov Barak, Dana Kaplan, Arie Ordentlich, more

Chemico-Biological Interactions > 2005 > 157-158 > Complete > 123-131

Functional analysis of the HuAChE active center architecture revealed that accommodation of structurally diverse substrates and other ligands is achieved through interactions with specific subsites such as the acyl pocket, cation binding site, hydrophobic site or the oxyanion hole. Recent studies have begun to unravel the role of this active center architecture in maintaining the optimal catalytic...

article

The role of AChE active site gorge in determining stereoselectivity of charged and noncharged VX enantiomers

Arie Ordentlich, Dov Barak, Gali Sod-Moriah, Dana Kaplan, more

Chemico-Biological Interactions > 2005 > 157-158 > Complete > 191-198

The reactivity of human acetylcholinesterase (HuAChE) toward the chemical warfare agent VX {O-ethyl S-[2-(diisopropylamino)ethyl] methyl-phosphonothioate} and its stereoselectivity toward the P ^S -enantiomer were investigated by examining the reactivity of HuAChE and its mutant derivatives toward purified enantiomers of VX and its noncharged isostere nc-VX [O-ethyl S-(3-isopropyl-4-methyl-pentyl)...

article

Host-regulated disposition of mammalian AChEs

Chanoch Kronman, Ofer Cohen, Baruch Velan, Avigdor Shafferman

Chemico-Biological Interactions > 2005 > 157-158 > Complete > 51-55

Primates are characterized by a paucity of soluble acetylcholinesterase (AChE) in the circulation at the adult stage, where the predominant circulating cholinesterase is butyrylcholinesterase. In recent years, we subjected recombinant human and bovine acetylcholinesterase to extensive pharmacokinetic studies in mice, an animal system which also displays very low levels of circulating AChE. In this...

article

Stereoselectivity toward VX Is Determined by Interactions with Residues of the Acyl Pocket as Well as of the Peripheral Anionic Site of AChE ^†

Arie Ordentlich, Dov Barak, Gali Sod-Moriah, Dana Kaplan, more

Biochemistry > 2004 > 43 > 35 > 11255 - 11265

article

Is Aromaticity Essential for Trapping the Catalytic Histidine 447 in Human Acetylcholinesterase? ^†

Dana Kaplan, Dov Barak, Arie Ordentlich, Chanoch Kronman, more

Biochemistry > 2004 > 43 > 11 > 3129 - 3136

article

Does “Butyrylization” of Acetylcholinesterase through Substitution of the Six Divergent Aromatic Amino Acids in the Active Center Gorge Generate an Enzyme Mimic of Butyrylcholinesterase? ^†

Dana Kaplan, Arie Ordentlich, Dov Barak, Naomi Ariel, more

Biochemistry > 2001 > 40 > 25 > 7433 - 7445

article

Theoretical and experimental investigations of electrostatic effects on acetylcholinesterase catalysis and inhibition

Siobhan Malany, Nathan Baker, Michelle Verweyst, Rohit Medhekar, more

Chemico-Biological Interactions > 1999 > 119-120 > Complete > 99-110

The role of electrostatics in the function of acetylcholinesterase (AChE) has been investigated by both theoretical and experimental approaches. Second-order rate constants (k _E =k _cat /K _m ) for acetylthiocholine (ATCh) turnover have been measured as a function of ionic strength of the reaction medium for wild-type and mutant AChEs. Also, binding and dissociation rate constants...

article

Engineering resistance to 'aging' of phosphylated human acetylcholinesterase Role of hydrogen bond network in the active center

Arie Ordentlich, Chanoch Kronman, Dov Barak, Dana Stein, more

FEBS Letters > 1993 > 334 > 2 > 215-220

Recombinant human acetylcholinesterase (HuAChE) and selected mutants (E202Q, Y337A, E450A) were studied with respect to catalytic activity towards charged and noncharged substrates, phosphylation with organophosphorus (OP) inhibitors and subsequent aging of the OP-conjugates. Amino acid E450, unlike residues E202 and Y337, is not within interaction distance from the active center. Yet, the bimolecular...

Filter options

Publication date

Set your own date range

Keywords

RICIN (7)
ACETYLCHOLINESTERASE (4)
ANTIBODIES (3)
ABRIN (2)
MUTAGENESIS (2)
PHARMACOKINETICS (2)
POLYETHYLENE GLYCOL (2)
PULMONARY (2)
TRUNCATED CDNA (2)
28S RRNA (1)
28SRRNA (1)
ACHE (1)
ACYL-POCKET (1)
ANALOG BINDING (1)
AROMATIC TRAPPING (1)
BALF (1)
BIOSCAVENGER (1)
BLOOD SAMPLE (1)
CARBAMATES (1)
CATALYSIS (1)
CATALYTIC TRIAD (1)
CATIONIC-BINDING SUBSITE (1)
CHARGED LEAVING GROUP (1)
CHIMERIC ANTIBODIES (1)
CIRCULATING CELL-FREE RRNA (1)
COMBINED THERAPY (1)
DEPURINATED 28S RRNA (1)
DEPURINATION (1)
DEPURINATION OF A SPECIFIC ADENOSINE (1)
DONEPEZIL (1)
DOXYCYCLINE (1)
ELECTROSTATICS (1)
GALANTHAMINE (1)
H-BOND NETWORK (1)
HYPOLYSINE ACHE (1)
IL-6 (1)
IMMUNOGENICITY (1)
LIGAND DIFFUSION (1)
LUNG (1)
N-GLYCAN (1)
NEUTRALIZATION (1)
OP-BIOSCAVENGER (1)
ORGANOPHOSPHORUS INHIBITOR (1)
PERIPHERAL ANIONIC SITE (PAS) (1)
PHOSPHATE INHIBITORS (1)
POST-EXPOSURE THERAPY (1)
PROTEIN OLIGOMERIZATION (1)
PYRIDOSTIGMINE (1)
REVERSE TRANSCRIPTION-LIGASE-PCR ASSAY (1)
RIVASTIGMINE (1)
SERINE HYDROLASE (1)
SERINE HYDROLASES (1)
SIALIC ACID (1)
SOMAN (1)
STEREOSELECTIVITY (1)
TOXIN (1)
TRANSITION STATE (1)
TRISOL ASSAY (1)
VACCINE (1)
more

Data set

Elsevier (14)
ACS (3)
Springer (2)

INFONA - science communication portal

Search results for: Chanoch Kronman

Add recipient

Sending message cancelled

Are you sure you want to cancel sending this message?

Send message

Filter options

Publication date

Date range setting

Set the date range to filter the displayed results. You can set a starting date, ending date or both. You can enter the dates manually or choose them from the calendar.

Keywords

Data set

Journal

Reporting an error / abuse

Sending the report failed

Accessibility options