• Something wrong with this record ?

Helicobacter pylori Xanthine-Guanine-Hypoxanthine Phosphoribosyltransferase-A Putative Target for Drug Discovery against Gastrointestinal Tract Infections

DT. Keough, SJ. Wun, O. Baszczyňski, WS. Eng, P. Špaček, S. Panjikar, L. Naesens, R. Pohl, D. Rejman, D. Hocková, RL. Ferrero, LW. Guddat

. 2021 ; 64 (9) : 5710-5729. [pub] 20210423

Language English Country United States

Document type Journal Article, Research Support, Non-U.S. Gov't

Persistent link   https://www.medvik.cz/link/bmc21018612

Helicobacter pylori (Hp) is a human pathogen that lives in the gastric mucosa of approximately 50% of the world's population causing gastritis, peptic ulcers, and gastric cancer. An increase in resistance to current drugs has sparked the search for new Hp drug targets and therapeutics. One target is the disruption of nucleic acid production, which can be achieved by impeding the synthesis of 6-oxopurine nucleoside monophosphates, the precursors of DNA and RNA. These metabolites are synthesized by Hp xanthine-guanine-hypoxanthine phosphoribosyltransferase (XGHPRT). Here, nucleoside phosphonates have been evaluated, which inhibit the activity of this enzyme with Ki values as low as 200 nM. The prodrugs of these compounds arrest the growth of Hp at a concentration of 50 μM in cell-based assays. The kinetic properties of HpXGHPRT have been determined together with its X-ray crystal structure in the absence and presence of 9-[(N-3-phosphonopropyl)-aminomethyl-9-deazahypoxanthine, providing a basis for new antibiotic development.

References provided by Crossref.org

000      
00000naa a2200000 a 4500
001      
bmc21018612
003      
CZ-PrNML
005      
20210830100215.0
007      
ta
008      
210728s2021 xxu f 000 0|eng||
009      
AR
024    7_
$a 10.1021/acs.jmedchem.0c02184 $2 doi
035    __
$a (PubMed)33891818
040    __
$a ABA008 $b cze $d ABA008 $e AACR2
041    0_
$a eng
044    __
$a xxu
100    1_
$a Keough, Dianne T $u The School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane 4072, Queensland, Australia
245    10
$a Helicobacter pylori Xanthine-Guanine-Hypoxanthine Phosphoribosyltransferase-A Putative Target for Drug Discovery against Gastrointestinal Tract Infections / $c DT. Keough, SJ. Wun, O. Baszczyňski, WS. Eng, P. Špaček, S. Panjikar, L. Naesens, R. Pohl, D. Rejman, D. Hocková, RL. Ferrero, LW. Guddat
520    9_
$a Helicobacter pylori (Hp) is a human pathogen that lives in the gastric mucosa of approximately 50% of the world's population causing gastritis, peptic ulcers, and gastric cancer. An increase in resistance to current drugs has sparked the search for new Hp drug targets and therapeutics. One target is the disruption of nucleic acid production, which can be achieved by impeding the synthesis of 6-oxopurine nucleoside monophosphates, the precursors of DNA and RNA. These metabolites are synthesized by Hp xanthine-guanine-hypoxanthine phosphoribosyltransferase (XGHPRT). Here, nucleoside phosphonates have been evaluated, which inhibit the activity of this enzyme with Ki values as low as 200 nM. The prodrugs of these compounds arrest the growth of Hp at a concentration of 50 μM in cell-based assays. The kinetic properties of HpXGHPRT have been determined together with its X-ray crystal structure in the absence and presence of 9-[(N-3-phosphonopropyl)-aminomethyl-9-deazahypoxanthine, providing a basis for new antibiotic development.
650    _2
$a sekvence aminokyselin $7 D000595
650    _2
$a antibakteriální látky $x chemie $x metabolismus $x farmakologie $x terapeutické užití $7 D000900
650    _2
$a bakteriální proteiny $x chemie $x metabolismus $7 D001426
650    _2
$a vazebná místa $7 D001665
650    _2
$a krystalografie rentgenová $7 D018360
650    _2
$a gastrointestinální nemoci $x farmakoterapie $x mikrobiologie $x patologie $7 D005767
650    _2
$a infekce vyvolané Helicobacter pylori $x farmakoterapie $x patologie $7 D016481
650    _2
$a Helicobacter pylori $x účinky léků $x enzymologie $7 D016480
650    _2
$a lidé $7 D006801
650    _2
$a hypoxanthinfosforibosyltransferasa $x chemie $x metabolismus $7 D007041
650    _2
$a hypoxanthiny $x chemie $x metabolismus $x farmakologie $x terapeutické užití $7 D007042
650    _2
$a kinetika $7 D007700
650    _2
$a simulace molekulární dynamiky $7 D056004
650    _2
$a organofosfonáty $x chemie $x metabolismus $x farmakologie $x terapeutické užití $7 D063065
650    _2
$a pentosyltransferasy $x chemie $x metabolismus $7 D010430
650    _2
$a prekurzory léčiv $x chemie $x metabolismus $x farmakologie $x terapeutické užití $7 D011355
650    _2
$a sekvenční seřazení $7 D016415
650    _2
$a vztahy mezi strukturou a aktivitou $7 D013329
655    _2
$a časopisecké články $7 D016428
655    _2
$a práce podpořená grantem $7 D013485
700    1_
$a Wun, Shun Jie $u The School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane 4072, Queensland, Australia
700    1_
$a Baszczyňski, Ondřej $u Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague 6 CZ-166 10, Czech Republic
700    1_
$a Eng, Wai Soon $u The School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane 4072, Queensland, Australia
700    1_
$a Špaček, Petr $u Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague 6 CZ-166 10, Czech Republic
700    1_
$a Panjikar, Santosh $u Australian Synchrotron, ANSTO, 800 Blackburn Road, Clayton 3168, Victoria, Australia $u Department of Biochemistry and Molecular Biology, Monash University, Clayton 3800, Australia
700    1_
$a Naesens, Lieve $u Katholieke Universiteit, Leuven, Rega Institute for Medical Research, Leuven 3000, Belgium
700    1_
$a Pohl, Radek $u Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague 6 CZ-166 10, Czech Republic
700    1_
$a Rejman, Dominik $u Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague 6 CZ-166 10, Czech Republic
700    1_
$a Hocková, Dana $u Institute of Organic Chemistry and Biochemistry, Academy of Sciences of the Czech Republic, Prague 6 CZ-166 10, Czech Republic
700    1_
$a Ferrero, Richard L $u Hudson Institute of Medical Research, Clayton 3800, Victoria, Australia $u Department of Molecular and Translational Sciences, Monash University, Clayton 3800, Australia $u Biomedicine Discovery Institute, Department of Microbiology, Monash University, Clayton 3800, Australia
700    1_
$a Guddat, Luke W $u The School of Chemistry and Molecular Biosciences, The University of Queensland, Brisbane 4072, Queensland, Australia
773    0_
$w MED00010049 $t Journal of medicinal chemistry $x 1520-4804 $g Roč. 64, č. 9 (2021), s. 5710-5729
856    41
$u https://pubmed.ncbi.nlm.nih.gov/33891818 $y Pubmed
910    __
$a ABA008 $b sig $c sign $y p $z 0
990    __
$a 20210728 $b ABA008
991    __
$a 20210830100215 $b ABA008
999    __
$a ok $b bmc $g 1689644 $s 1139058
BAS    __
$a 3
BAS    __
$a PreBMC
BMC    __
$a 2021 $b 64 $c 9 $d 5710-5729 $e 20210423 $i 1520-4804 $m Journal of medicinal chemistry $n J Med Chem $x MED00010049
LZP    __
$a Pubmed-20210728

Find record

Citation metrics

Archiving options