Regioisomerization of Antimalarial Drug WR99210 Explains the Inactivity of a Commercial Stock-Reference-Cited by-同舟云学术

Regioisomerization of Antimalarial Drug WR99210 Explains the Inactivity of a Commercial Stock

Published:2020-12-16 Issue:1 Volume:65 Page:
ISSN:0066-4804
Container-title:Antimicrobial Agents and Chemotherapy
language:en
Short-container-title:Antimicrob Agents Chemother

Author:

Remcho T. Parks¹^ORCID,Guggilapu Sravanthi D.²^ORCID,Cruz Phillip³,Nardone Glenn A.⁴,Heffernan Gavin⁵,O’Connor Robert D.²,Bewley Carole A.²^ORCID,Wellems Thomas E.¹^ORCID,Lane Kristin D.¹^ORCID

Affiliation:

1. Laboratory of Malaria and Vector Research, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA

2. Laboratory of Bioorganic Chemistry, National Institute of Diabetes and Digestive and Kidney Diseases, National Institutes of Health, Bethesda, Maryland, USA

3. Office of Cyber Infrastructure and Computational Biology, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Bethesda, Maryland, USA

4. Research Technologies Branch, National Institute of Allergy and Infectious Diseases, National Institutes of Health, Rockville, Maryland, USA

5. Jacobus Pharmaceutical Company, Inc., Princeton, New Jersey, USA

Abstract

WR99210, a former antimalarial drug candidate now widely used for the selection of Plasmodium transfectants, selectively targets the parasite’s dihydrofolate reductase thymidine synthase bifunctional enzyme (DHFR-TS) but not human DHFR, which is not fused with TS. Accordingly, WR99210 and plasmids expressing the human dhfr gene have become valued tools for the genetic modification of parasites in the laboratory. Concerns over the ineffectiveness of WR99210 from some sources encouraged us to investigate the biological and chemical differences of supplies from two different companies (compounds 1 and 2).

Publisher

American Society for Microbiology

Subject

Infectious Diseases,Pharmacology (medical),Pharmacology

Link

https://journals.asm.org/doi/pdf/10.1128/AAC.01385-20

Reference32 articles.

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