Structure-based design of guanosine analogue inhibitors targeting GTP cyclohydrolase IB towards a new class of antibiotics.

George N Samaan, Naduni Paranagama, Ayesha Haque, David A Hecht, Manal A Swairjo, Byron W Purse

Abstract read

In one paragraph

Article in Bioorganic & medicinal chemistry letters, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

0numbers the graph read from it

0cells of the map it votes in

0citing papers in PubMed

–field-weighted citation impact

1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

0 citing papers in PubMed.

No citing paper in PubMed yet.

4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

6 authors.

George N SamaanDepartment of Chemistry and Biochemistry and the Viral Information Institute, San Diego State University, San Diego, CA 92182, USA.

Naduni ParanagamaDepartment of Chemistry and Biochemistry and the Viral Information Institute, San Diego State University, San Diego, CA 92182, USA.

Ayesha HaqueDepartment of Chemistry and Biochemistry and the Viral Information Institute, San Diego State University, San Diego, CA 92182, USA.

David A HechtDepartment of Chemistry and Biochemistry, San Diego State University, San Diego, CA 92182, USA; Department of Chemistry, Southwestern College, Chula Vista, CA 92120, USA.

Manal A SwairjoDepartment of Chemistry and Biochemistry and the Viral Information Institute, San Diego State University, San Diego, CA 92182, USA. Electronic address: mswairjo@sdsu.edu.

Byron W PurseDepartment of Chemistry and Biochemistry and the Viral Information Institute, San Diego State University, San Diego, CA 92182, USA. Electronic address: bpurse@sdsu.edu.

Funding

RNA modification: Structure and MechanismR01GM110588 · NIGMS · WESTERN UNIVERSITY OF HEALTH SCIENCES · PI SWAIRJO, MANAL A · 2014 to 2024

$3.9M

NIGMS NIH HHS R01 GM110588

6 · The paper itself

Abstract

GTP cyclohydrolase (GCYH-I) is an enzyme in the folate biosynthesis pathway that has not been previously exploited as an antibiotic target, although several pathogens including N. gonorrhoeae use a form of the enzyme GCYH-IB that is structurally distinct from the human homologue GCYH-IA. A comparison of the crystal structures of GCYH-IA and -IB with the nM inhibitor 8-oxo-GTP bound shows that the active site of GCYH-IB is larger and differently shaped. Based on this structural information, we designed and synthesized a small set of 8-oxo-G derivatives with ether linkages at O

Indexed as

Anti-Bacterial AgentsGTP CyclohydrolaseGuanosineHumansMolecular StructureStructure-Activity RelationshipAnti-Bacterial AgentsGTP CyclohydrolaseGuanosineAntibioticFolateGTPNucleosideResistance

Identifiers

PMID31771800

DOI10.1016/j.bmcl.2019.126818

PMCPMC6942202

What OpenQuestion holds

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.