دورية أكاديمية
أعرض في EDS

Shotgun Kinetic Target-Guided Synthesis Approach Enables the Discovery of Small-Molecule Inhibitors against Pathogenic Free-Living Amoeba Glucokinases.

التفاصيل البيبلوغرافية
العنوان: Shotgun Kinetic Target-Guided Synthesis Approach Enables the Discovery of Small-Molecule Inhibitors against Pathogenic Free-Living Amoeba Glucokinases.
المؤلفون: Kassu M; Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States., Parvatkar PT; Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States., Milanes J; Eukaryotic Pathogens Innovation Center, Department of Genetics and Biochemistry, Clemson University, Clemson, South Carolina 29634, United States., Monaghan NP; Eukaryotic Pathogens Innovation Center, Department of Genetics and Biochemistry, Clemson University, Clemson, South Carolina 29634, United States., Kim C; Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States., Dowgiallo M; Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States., Zhao Y; Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States., Asakawa AH; Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts 02115, United States., Huang L; Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States., Wagner A; Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States., Miller B; Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States., Carter K; Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States., Barrett KF; Center for Emerging and Re-emerging Infectious Diseases (CERID), Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98109, United States., Tillery LM; Center for Emerging and Re-emerging Infectious Diseases (CERID), Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98109, United States., Barrett LK; Center for Emerging and Re-emerging Infectious Diseases (CERID), Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98109, United States., Phan IQ; Center for Global Infectious Diseases Research, Seattle Children's Research Center, Seattle, Washington 98109, United States., Subramanian S; Center for Global Infectious Diseases Research, Seattle Children's Research Center, Seattle, Washington 98109, United States., Myler PJ; Center for Global Infectious Diseases Research, Seattle Children's Research Center, Seattle, Washington 98109, United States., Van Voorhis WC; Center for Emerging and Re-emerging Infectious Diseases (CERID), Division of Allergy and Infectious Diseases, Department of Medicine, University of Washington School of Medicine, Seattle, Washington 98109, United States., Leahy JW; Department of Chemistry, University of South Florida, Tampa, Florida 33620, United States., Rice CA; Department of Comparative Pathobiology, College of Veterinary Medicine, Purdue University, West Lafayette, Indiana 47907, United States.; Purdue Institute for Drug Discovery (PIDD), Purdue University, West Lafayette, Indiana 47907, United States.; Purdue Institute of Inflammation, Immunology and Infectious Disease (PI4D), Purdue University, West Lafayette, Indiana 47907, United States.; Department of Cellular Biology, University of Georgia, Athens, Georgia 30602, United States., Kyle DE; Department of Cellular Biology, University of Georgia, Athens, Georgia 30602, United States., Morris J; Eukaryotic Pathogens Innovation Center, Department of Genetics and Biochemistry, Clemson University, Clemson, South Carolina 29634, United States., Manetsch R; Department of Chemistry and Chemical Biology, Northeastern University, Boston, Massachusetts 02115, United States.; Department of Pharmaceutical Sciences, Northeastern University, Boston, Massachusetts 02115, United States.; Center for Drug Discovery, Northeastern University, Boston, Massachusetts 02115, United States.; Barnett Institute of Chemical and Biological Analysis, Northeastern University, Boston, Massachusetts 02115, United States.
المصدر: ACS infectious diseases [ACS Infect Dis] 2023 Nov 10; Vol. 9 (11), pp. 2190-2201. Date of Electronic Publication: 2023 Oct 11.
نوع المنشور: Journal Article; Research Support, N.I.H., Extramural
اللغة: English
بيانات الدورية: Publisher: ACS Publications Country of Publication: United States NLM ID: 101654580 Publication Model: Print-Electronic Cited Medium: Internet ISSN: 2373-8227 (Electronic) Linking ISSN: 23738227 NLM ISO Abbreviation: ACS Infect Dis Subsets: MEDLINE
أسماء مطبوعة: Original Publication: Washington, DC : ACS Publications, [2015]-
مواضيع طبية MeSH: Amoeba* , Naegleria fowleri* , Balamuthia mandrillaris* , Acanthamoeba castellanii*, Humans ; Glucokinase
مستخلص: Pathogenic free-living amoebae (pFLA) can cause life-threatening central nervous system (CNS) infections and warrant the investigation of new chemical agents to combat the rise of infection from these pathogens. Naegleria fowleri glucokinase ( Nf Glck), a key metabolic enzyme involved in generating glucose-6-phosphate, was previously identified as a potential target due to its limited sequence similarity with human Glck ( Hs Glck). Herein, we used our previously demonstrated multifragment kinetic target-guided synthesis (KTGS) screening strategy to identify inhibitors against pFLA glucokinases. Unlike the majority of previous KTGS reports, our current study implements a "shotgun" approach, where fragments were not biased by predetermined binding potentials. The study resulted in the identification of 12 inhibitors against 3 pFLA glucokinase enzymes─ Nf Glck, Balamuthia mandrillaris Glck ( Bm Glck), and Acanthamoeba castellanii Glck ( Ac Glck). This work demonstrates the utility of KTGS to identify small-molecule binders for biological targets where resolved X-ray crystal structures are not readily accessible.
References: J Am Chem Soc. 2003 Dec 24;125(51):15811-21. (PMID: 14677972)
J Med Chem. 2023 Apr 13;66(7):5196-5207. (PMID: 37000900)
Future Med Chem. 2016;8(4):381-404. (PMID: 26877247)
Mol Biosyst. 2013 May;9(5):940-3. (PMID: 23192606)
Angew Chem Int Ed Engl. 2002 Mar 15;41(6):1053-7. (PMID: 12491310)
J Am Chem Soc. 2015 Dec 23;137(50):15624-7. (PMID: 26632868)
Chem Commun (Camb). 2014 Feb 25;50(16):2043-5. (PMID: 24418813)
J Antibiot (Tokyo). 2009 May;62(5):277-82. (PMID: 19329983)
Angew Chem Int Ed Engl. 2020 Jul 20;59(30):12293-12307. (PMID: 32255543)
ACS Med Chem Lett. 2018 Aug 13;9(9):907-911. (PMID: 30258539)
Chem Commun (Camb). 2012 Feb 1;48(10):1526-8. (PMID: 21892513)
J Eukaryot Microbiol. 1993 Jul-Aug;40(4):504-14. (PMID: 8330028)
Nat Commun. 2015 Sep 23;6:8250. (PMID: 26394692)
ACS Chem Biol. 2010 Nov 19;5(11):1007-13. (PMID: 20704273)
Antimicrob Agents Chemother. 2019 Apr 25;63(5):. (PMID: 30783001)
Chemistry. 2020 Nov 17;26(64):14585-14593. (PMID: 32428268)
J Am Chem Soc. 2008 Oct 22;130(42):13820-1. (PMID: 18811158)
Angew Chem Int Ed Engl. 2006 Feb 20;45(9):1435-9. (PMID: 16425339)
ACS Med Chem Lett. 2013 Jan 15;4(2):274-7. (PMID: 24900659)
Angew Chem Int Ed Engl. 2022 Sep 26;61(39):e202203560. (PMID: 35904863)
Antimicrob Agents Chemother. 2022 Jun 21;66(6):e0237321. (PMID: 35604214)
Nat Commun. 2019 Jan 8;10(1):66. (PMID: 30622248)
Nat Commun. 2017 Dec;8(1):1. (PMID: 28232747)
Pathogens. 2020 Jun 16;9(6):. (PMID: 32560115)
Structure. 2012 Jun 6;20(6):1107-17. (PMID: 22608967)
J Org Chem. 2007 Feb 2;72(3):765-74. (PMID: 17253793)
Parasite. 2015;22:10. (PMID: 25687209)
Trans R Soc Trop Med Hyg. 1972;66(2):193-213. (PMID: 4558822)
Clin Infect Dis. 2016 Mar 15;62(6):774-6. (PMID: 26679626)
Chem Soc Rev. 2010 Apr;39(4):1272-9. (PMID: 20349533)
J Pediatric Infect Dis Soc. 2015 Dec;4(4):e68-75. (PMID: 26582886)
ChemMedChem. 2020 Feb 17;15(4):370-375. (PMID: 31774938)
Angew Chem Int Ed Engl. 2004 Dec 17;44(1):116-20. (PMID: 15599912)
J Med Chem. 1996 Jul 19;39(15):2887-93. (PMID: 8709122)
ChemMedChem. 2013 Jan;8(1):43-8. (PMID: 23208787)
J Chem Inf Model. 2010 May 24;50(5):742-54. (PMID: 20426451)
ACS Chem Biol. 2011 Jul 15;6(7):724-32. (PMID: 21506574)
ACS Med Chem Lett. 2018 Mar 08;9(4):351-353. (PMID: 29670699)
FEMS Immunol Med Microbiol. 2007 Jun;50(1):1-26. (PMID: 17428307)
J Am Chem Soc. 2012 Apr 18;134(15):6732-40. (PMID: 22394239)
ACS Chem Neurosci. 2010 Jun 16;1(6):435-49. (PMID: 22778837)
Chemistry. 2019 Sep 20;25(53):12380-12393. (PMID: 31298443)
J Am Chem Soc. 2016 Mar 9;138(9):3136-44. (PMID: 26878192)
J Am Chem Soc. 2009 May 27;131(20):6989-96. (PMID: 19413317)
Korean J Parasitol. 2009 Oct;47 Suppl:S21-8. (PMID: 19885332)
Angew Chem Int Ed Engl. 2001 May 4;40(9):1774-1776. (PMID: 11353508)
Chemistry. 2022 Nov 25;28(66):e202202259. (PMID: 35989238)
Nat Commun. 2017 Jul 14;8:16103. (PMID: 28706243)
Pediatrics. 2015 Mar;135(3):e744-8. (PMID: 25667249)
Angew Chem Int Ed Engl. 2017 Mar 20;56(13):3718-3722. (PMID: 28199769)
معلومات مُعتمدة: 75N93022C00036 United States AI NIAID NIH HHS
فهرسة مساهمة: Keywords: glucokinases; kinetic target-guided synthesis; multifragment screening; small molecule inhibitors; sulfo-click reaction
المشرفين على المادة: EC 2.7.1.2 (Glucokinase)
تواريخ الأحداث: Date Created: 20231011 Date Completed: 20231113 Latest Revision: 20240210
رمز التحديث: 20240210
مُعرف محوري في PubMed: PMC10644346
DOI: 10.1021/acsinfecdis.3c00284
PMID: 37820055
قاعدة البيانات: MEDLINE
الوصف
تدمد:2373-8227
DOI:10.1021/acsinfecdis.3c00284