Choi SK

References (8)

Title : Dual acting oximes designed for therapeutic decontamination of reactive organophosphates via catalytic inactivation and acetylcholinesterase reactivation - Cannon_2021_RSC.Med.Chem_12_1592
Author(s) : Cannon J , Tang S , Yang K , Harrison R , Choi SK
Ref : RSC Med Chem , 12 :1592 , 2021
Abstract : A conventional approach in the therapeutic decontamination of reactive organophosphate (OP) relies on chemical OP degradation by oxime compounds. However, their efficacy is limited due to their lack of activity in the reactivation of acetylcholinesterase (AChE), the primary target of OP. Here, we describe a set of alpha-nucleophile oxime derivatives which are newly identified for such dual modes of action. Thus, we prepared a 9-member oxime library, each composed of an OP-reactive oxime core linked to an amine-terminated scaffold, which varied through an N-alkyl functionalization. This library was screened by enzyme assays performed with human and electric eel subtypes of OP-inactivated AChE, which led to identifying three oxime leads that displayed significant enhancements in reactivation activity comparable to 2-PAM. They were able to reactivate both enzymes inactivated by three OP types including paraoxon, chlorpyrifos and malaoxon, suggesting their broad spectrum of OP susceptibility. All compounds in the library were able to retain catalytic reactivity in paraoxon inactivation by rates increased up to 5 or 8-fold relative to diacetylmonoxime (DAM) under controlled conditions at pH (8.0, 10.5) and temperature (17, 37 degreesC). Finally, selected lead compounds displayed superb efficacy in paraoxon decontamination on porcine skin in vitro. In summary, we addressed an unmet need in therapeutic OP decontamination by designing and validating a series of congeneric oximes that display dual modes of action.
ESTHER : Cannon_2021_RSC.Med.Chem_12_1592
PubMedSearch : Cannon_2021_RSC.Med.Chem_12_1592
PubMedID: 34671741

Title : Caged Oxime Reactivators Designed for the Light Control of Acetylcholinesterase Reactivation - Cannon_2021_Photochem.Photobiol__
Author(s) : Cannon J , Tang S , Choi SK
Ref : Photochem Photobiol , : , 2021
Abstract : Despite its promising role in the active control of biological functions by light, photocaging remains untested in acetylcholinesterase (AChE), a key enzyme in the cholinergic family. Here, we describe synthesis, photochemical properties, and biochemical activities of two caged oxime compounds applied in the photocontrolled reactivation of the AChE inactivated by reactive organophosphate. Each of these consists of a photocleavable coumarin cage tethered to a known oxime reactivator for AChE that belongs in an either 2-(hydroxyimino)acetamide or pyridiniumaldoxime class. Of these, the first caged compound was able to successfully go through oxime uncaging upon irradiation at long wavelength ultraviolet light (365 nm) or visible light (420 nm). It was further evaluated in AChE assays in vitro under variable light conditions to define its activity in the photocontrolled reactivation of paraoxon-inactivated AChE. This assay result showed its lack of activity in the dark but its induction of activity under light conditions only. In summary, this article reports a first class of light-activatable modulators for AChE and it offers assay methods and novel insights that help to achieve an effective design of caged compounds in the enzyme control.
ESTHER : Cannon_2021_Photochem.Photobiol__
PubMedSearch : Cannon_2021_Photochem.Photobiol__
PubMedID: 34558680

Title : Shielded alpha-Nucleophile Nanoreactor for Topical Decontamination of Reactive Organophosphate - Wong_2020_ACS.Appl.Mater.Interfaces_12_33500
Author(s) : Wong PT , Tang S , Cannon J , Yang K , Harrison R , Ruge M , O'Konek JJ , Choi SK
Ref : ACS Appl Mater Interfaces , 12 :33500 , 2020
Abstract : Here, we describe a nanoscale reactor strategy with a topical application in the therapeutic decontamination of reactive organophosphates (OPs) as chemical threat agents. It involves functionalization of poly(amidoamine) dendrimer through a combination of its partial PEG shielding and exhaustive conjugation with an OP-reactive alpha-nucleophile moiety at its peripheral branches. We prepared a 16-member library composed of two alpha-nucleophile classes (oxime, hydroxamic acid), each varying in its reactor valency (43-176 reactive units per nanoparticle), and linker framework for alpha-nucleophile tethering. Their mechanism for OP inactivation occurred via nucleophilic catalysis as verified against P-O and P-S bonded OPs including paraoxon-ethyl (POX), malaoxon, and omethoate by (1)H NMR spectroscopy. Screening their reactivity for POX inactivation was performed under pH- and temperature-controlled conditions, which resulted in identifying 13 conjugates, each showing shorter POX half-life up to 2 times as compared to a reference Dekon 139 at pH 10.5, 37 degreesC. Of these, 10 conjugates were further confirmed for greater efficacy in POX decontamination experiments performed in two skin models, porcine skin and an artificial human microtissue. Finally, a few lead conjugates were selected and demonstrated for their biocompatibility in vitro as evident with lack of skin absorption, no inhibition of acetylcholinesterase (AChE), and no cytotoxicity in human neuroblastoma cells. In summary, this study presents a novel nanoreactor library, its screening methods, and identification of potent lead conjugates with potential for therapeutic OP decontamination.
ESTHER : Wong_2020_ACS.Appl.Mater.Interfaces_12_33500
PubMedSearch : Wong_2020_ACS.Appl.Mater.Interfaces_12_33500
PubMedID: 32603588

Title : Hydrophilic scaffolds of oxime as the potent catalytic inactivator of reactive organophosphate - Tang_2019_Chem.Biol.Interact_297_67
Author(s) : Tang S , Wong PT , Cannon J , Yang K , Bowden S , Bhattacharjee S , O'Konek JJ , Choi SK
Ref : Chemico-Biological Interactions , 297 :67 , 2019
Abstract : Despite its efficacy as a skin decontaminant of reactive organophosphates (OP), Dekon 139-a potassium salt of 2,3-butanedione monooxime (DAM)-is associated with adverse events related to percutaneous absorption largely due to its small size and lipophilicity. In order to address this physicochemical issue, we synthesized and evaluated the activity of a focused library of 14 hydrophilic oxime compounds, each designed with either a DAM or monoisonitrosoacetone (MINA) oxime tethered to a polar or charged scaffold in order to optimize the size, hydrophilicity, and oxime acidity. High-throughput colorimetric assays were performed with paraoxon (POX) as a model OP to determine the kinetics of POX inactivation by these compounds under various pH and temperature conditions. This primary screening led to the identification of 6 lead compounds, predominantly in the MINA series, which displayed superb catalytic activity by reducing the POX half-life (t1/2) by 2-3 fold relative to Dekon 139. Our mechanistic studies show that POX inactivation by the oxime compounds occurred faster at a higher temperature and in a pH-dependent manner in which the negatively charged oximate species is>/=10-fold more effective than the neutral oxime species. Lastly, using one of the lead compounds, we demonstrated its promising efficacy for POX decontamination in porcine skin ex vivo, and showed its potent ability to protect acetylcholine esterase (AChE) through POX inactivation. In summary, we report the rational design and chemical biological validation of novel hydrophilic oximes which address an unmet need in therapeutic OP decontamination.
ESTHER : Tang_2019_Chem.Biol.Interact_297_67
PubMedSearch : Tang_2019_Chem.Biol.Interact_297_67
PubMedID: 30393113

Title : Genome Sequence of the Acrystalliferous Bacillus thuringiensis Serovar Israelensis Strain 4Q7, Widely Used as a Recombination Host - Jeong_2014_Genome.Announc_2_e00231
Author(s) : Jeong H , Park SH , Choi SK
Ref : Genome Announc , 2 : , 2014
Abstract : Bacillus thuringiensis serovar israelensis is well known for its mosquitocidal activity and has long been used as a biopesticide. Herein, we present the genome sequence of B. thuringiensis serovar israelensis strain 4Q7, a plasmid-cured derivative with higher transformation efficiency than wild types.
ESTHER : Jeong_2014_Genome.Announc_2_e00231
PubMedSearch : Jeong_2014_Genome.Announc_2_e00231
PubMedID: 24699954

Title : Specific and Cooperative Interactions between Oximes and PAMAM Dendrimers As Demonstrated by (1)H NMR Study - Choi_2012_J.Phys.Chem.B_116_10387
Author(s) : Choi SK , Thomas TP , Leroueil P , Kotlyar A , van der Spek AF , Baker JR, Jr.
Ref : J Phys Chem B , 116 :10387 , 2012
Abstract : Oximes are important in the treatment of organophosphate (OP) poisoning, but have limited biological half-lives. Complexing these drugs with a macromolecule, such as a dendrimer, could improve their pharmacokinetics. The present study investigates the intermolecular interactions that drive the complexation of oxime-based drug molecules with fifth generation poly(amidoamine) (PAMAM) dendrimers. We performed steady-state binding studies of two molecules, pralidoxime and obidoxime, employing multiple NMR methods, including 1D titration, (1)H-(1)H 2D spectroscopy (COSY, NOESY), and (1)H diffusion-ordered spectroscopy (DOSY). Several important insights were gained in understanding the host-guest interactions occurring between the drug molecules and the polymer. First, the guest molecules bind to the dendrimer macromolecule through a specific interaction rather than through random, hydrophobic encapsulation. Second, this specificity is driven primarily by the electrostatic or H-bond interaction of the oxime at a dendrimer amine site. Also, the average strength for each drug and dendrimer interaction is affected by the surface modification of the polymer. Third, individual binding events between oximes and a dendrimer have a negative cooperative effect on subsequent oxime binding. In summary, this report provides a novel perspective important for designing host systems for drug delivery.
ESTHER : Choi_2012_J.Phys.Chem.B_116_10387
PubMedSearch : Choi_2012_J.Phys.Chem.B_116_10387
PubMedID: 22871033

Title : Genome sequence of the polymyxin-producing plant-probiotic rhizobacterium Paenibacillus polymyxa E681 - Kim_2010_J.Bacteriol_192_6103
Author(s) : Kim JF , Jeong H , Park SY , Kim SB , Park YK , Choi SK , Ryu CM , Hur CG , Ghim SY , Oh TK , Kim JJ , Park CS , Park SH
Ref : Journal of Bacteriology , 192 :6103 , 2010
Abstract : Paenibacillus polymyxa E681, a spore-forming, low-G+C, Gram-positive bacterium isolated from the rhizosphere of winter barley grown in South Korea, has great potential for agricultural applications due to its ability to promote plant growth and suppress plant diseases. Here we present the complete genome sequence of P. polymyxa E681. Its 5.4-Mb genome encodes functions specialized to the plant-associated lifestyle and characteristics that are beneficial to plants, such as the production of a plant growth hormone, antibiotics, and hydrolytic enzymes.
ESTHER : Kim_2010_J.Bacteriol_192_6103
PubMedSearch : Kim_2010_J.Bacteriol_192_6103
PubMedID: 20851896
Gene_locus related to this paper: paep6-e0ra24 , paep6-e0rkv6 , paep6-e0rmc7 , paep6-e0rmu8 , paeps-e3ebx3

Title : The complete genome sequence of the gram-positive bacterium Bacillus subtilis - Kunst_1997_Nature_390_249
Author(s) : Kunst F , Ogasawara N , Moszer I , Albertini AM , Alloni G , Azevedo V , Bertero MG , Bessieres P , Bolotin A , Borchert S , Borriss R , Boursier L , Brans A , Braun M , Brignell SC , Bron S , Brouillet S , Bruschi CV , Caldwell B , Capuano V , Carter NM , Choi SK , Cordani JJ , Connerton IF , Cummings NJ , Daniel RA , Denziot F , Devine KM , Dusterhoft A , Ehrlich SD , Emmerson PT , Entian KD , Errington J , Fabret C , Ferrari E , Foulger D , Fritz C , Fujita M , Fujita Y , Fuma S , Galizzi A , Galleron N , Ghim SY , Glaser P , Goffeau A , Golightly EJ , Grandi G , Guiseppi G , Guy BJ , Haga K , Haiech J , Harwood CR , Henaut A , Hilbert H , Holsappel S , Hosono S , Hullo MF , Itaya M , Jones L , Joris B , Karamata D , Kasahara Y , Klaerr-Blanchard M , Klein C , Kobayashi Y , Koetter P , Koningstein G , Krogh S , Kumano M , Kurita K , Lapidus A , Lardinois S , Lauber J , Lazarevic V , Lee SM , Levine A , Liu H , Masuda S , Mauel C , Medigue C , Medina N , Mellado RP , Mizuno M , Moestl D , Nakai S , Noback M , Noone D , O'Reilly M , Ogawa K , Ogiwara A , Oudega B , Park SH , Parro V , Pohl TM , Portelle D , Porwollik S , Prescott AM , Presecan E , Pujic P , Purnelle B , Rapoport G , Rey M , Reynolds S , Rieger M , Rivolta C , Rocha E , Roche B , Rose M , Sadaie Y , Sato T , Scanlan E , Schleich S , Schroeter R , Scoffone F , Sekiguchi J , Sekowska A , Seror SJ , Serror P , Shin BS , Soldo B , Sorokin A , Tacconi E , Takagi T , Takahashi H , Takemaru K , Takeuchi M , Tamakoshi A , Tanaka T , Terpstra P , Togoni A , Tosato V , Uchiyama S , Vandebol M , Vannier F , Vassarotti A , Viari A , Wambutt R , Wedler H , Weitzenegger T , Winters P , Wipat A , Yamamoto H , Yamane K , Yasumoto K , Yata K , Yoshida K , Yoshikawa HF , Zumstein E , Yoshikawa H , Danchin A
Ref : Nature , 390 :249 , 1997
Abstract : Bacillus subtilis is the best-characterized member of the Gram-positive bacteria. Its genome of 4,214,810 base pairs comprises 4,100 protein-coding genes. Of these protein-coding genes, 53% are represented once, while a quarter of the genome corresponds to several gene families that have been greatly expanded by gene duplication, the largest family containing 77 putative ATP-binding transport proteins. In addition, a large proportion of the genetic capacity is devoted to the utilization of a variety of carbon sources, including many plant-derived molecules. The identification of five signal peptidase genes, as well as several genes for components of the secretion apparatus, is important given the capacity of Bacillus strains to secrete large amounts of industrially important enzymes. Many of the genes are involved in the synthesis of secondary metabolites, including antibiotics, that are more typically associated with Streptomyces species. The genome contains at least ten prophages or remnants of prophages, indicating that bacteriophage infection has played an important evolutionary role in horizontal gene transfer, in particular in the propagation of bacterial pathogenesis.
ESTHER : Kunst_1997_Nature_390_249
PubMedSearch : Kunst_1997_Nature_390_249
PubMedID: 9384377
Gene_locus related to this paper: bacsu-CAH , bacsu-cbxnp , bacsu-lip , bacsu-LIPB , bacsu-PKSR , bacsu-pnbae , bacsu-PPSE , bacsu-srf4 , bacsu-srfac , bacsu-YBAC , bacsu-YBDG , bacsu-ybfk , bacsu-ycgS , bacsu-yczh , bacsu-YDEN , bacsu-ydjp , bacsu-yfhM , bacsu-yisY , bacsu-YITV , bacsu-yjau , bacsu-YJCH , bacsu-MHQD , bacsu-yqjl , bacsu-yqkd , bacsu-YRAK , bacsu-YTAP , bacsu-YTMA , bacsu-YTPA , bacsu-ytxm , bacsu-yugF , bacsu-YUII , bacsu-YUKL , bacsu-YVAK , bacsu-YvaM , bacsu-RsbQ