The DOI matches its Crossref record; 11 of the 11 references it cites were found in a registry or an index.
Amino acids in the dihydrofolate reductase-thymidylate synthase gene of Plasmodium falciparum involved in cycloguanil resistance differ from those involved in pyrimethamine resistance.
Open accessAbstract
Cycloguanil, the active metabolite of the antimalarial drug proguanil, is an inhibitor of dihydrofolate reductase as is another antimalarial, pyrimethamine. Its use has been limited by the rapid development of resistance by parasites around the world. We have determined the cycloguanil- and pyrimethamine-sensitivity status of 10 isolates of Plasmodium falciparum and have sequenced in all these isolates the dihydrofolate reductase (DHFR; 5,6,7,8-tetrahydrofolate: NADP+ oxidoreductase, EC 1.5.1.3) portion of the DHFR-thymidylate synthase (TS; 5,10-methylenetetrahydrofolate: dUMP C-methyltransferase, EC 2.1.1.45) gene. Instead of the known serine-to-asparagine change at position 108 that is important in pyrimethamine resistance, a serine-to-threonine change at the same position is found in cycloguanil-resistant isolates along with an alanine-to-valine change at position 16. We conclude that pyrimethamine and cycloguanil resistance most commonly involve alternative mutations at the same site. However, we also have identified a parasite with a unique set of changes that results in resistance to both drugs.
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Metadata
- Authors
- Foote, S. J., Galatis, D., & Cowman, A. F.
- Venue
- Proceedings of the National Academy of Sciences
- Published
- 1990-04
- Volume
- 87
- Issue
- 8
- Pages
- 3014-3017
- ISSN
- 0027-8424 (ISSN-L)
- 1091-6490
- OpenAlex
- W2033314986
- Cited by
- 301
- References
- 11
- FWCI
- 6.88
- Type
- journal article
- Language
- en
- Open access
- green
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- CoChat. (2026). Citation check: Amino acids in the dihydrofolate reductase-thymidylate synthase gene of Plasmodium falciparum involved in cycloguanil resistance differ from those involved in pyrimethamine resistance. https://app.cochat.ai/papers/10.1073/pnas.87.8.3014
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- Foote, S. J., Galatis, D., & Cowman, A. F. (1990). Amino acids in the dihydrofolate reductase-thymidylate synthase gene of Plasmodium falciparum involved in cycloguanil resistance differ from those involved in pyrimethamine resistance. Proceedings of the National Academy of Sciences. https://doi.org/10.1073/pnas.87.8.3014
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Bibliographic data: Semantic Scholar, OpenAlex, Crossref.
Contains information from the Semantic Scholar Academic Graph Datasets, made available under the ODC Attribution License (ODC-BY 1.0).
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