Evidence map›Paper›PMID 25987836›Full record

ArticleDrug design, development and therapy2015

Structure-activity exploration of a small-molecule Lipid II inhibitor.

Steven Fletcher, Wenbo Yu, Jing Huang, Steven M Kwasny, Jay Chauhan, Timothy J Opperman, Alexander D MacKerell, Erik P H de Leeuw

Open access · goldAbstract read
PubMed Full text at PMC Publisher
In one paragraph

Article in Drug design, development and therapy, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 5 papers.

0numbers the graph read from it
0cells of the map it votes in
5citing papers in PubMed
1.6field-weighted citation impact, top 18% of its field
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

5 citing papers in PubMed, 10 citations in OpenAlex.

  1. Article
  2. Computer-Aided Drug Design: An Update.Methods in molecular biology (Clifton, N.J.) · 2023
    Article
  3. Article
  4. Computer-Aided Drug Design Methods.Methods in molecular biology (Clifton, N.J.) · 2017
    Article
  5. Article
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

8 authors at 3 institutions in 2 countries.

Steven FletcherDepartment of Pharmaceutical Sciences, University of Maryland, School of Pharmacy, Baltimore, MD, USA.
Wenbo YuDepartment of Pharmaceutical Sciences, University of Maryland, School of Pharmacy, Baltimore, MD, USA ; Computer-Aided Drug Design Center, University of Maryland, School of Pharmacy, Baltimore, MD, USA.
Jing HuangDepartment of Pharmaceutical Sciences, University of Maryland, School of Pharmacy, Baltimore, MD, USA ; Computer-Aided Drug Design Center, University of Maryland, School of Pharmacy, Baltimore, MD, USA.
Steven M KwasnyMicrobiotix, Inc., Worcester, MA, USA.
Jay ChauhanDepartment of Pharmaceutical Sciences, University of Maryland, School of Pharmacy, Baltimore, MD, USA.
Timothy J OppermanMicrobiotix, Inc., Worcester, MA, USA.
Alexander D MacKerellDepartment of Pharmaceutical Sciences, University of Maryland, School of Pharmacy, Baltimore, MD, USA ; Computer-Aided Drug Design Center, University of Maryland, School of Pharmacy, Baltimore, MD, USA.
Erik P H de LeeuwInstitute of Human Virology and Department of Biochemistry and Molecular Biology, University of Maryland, School of Medicine, Baltimore, MD, USA.
University of Maryland, Baltimore · USMicrobiotix (United States) · USPharmaceutical Biotechnology (Czechia) · CZ

Funding

Molecular Basis of Human Defensins as Novel Lipid II Binding Peptide AntibioticsR21AI092033 · NIAID · UNIVERSITY OF MARYLAND BALTIMORE · PI DE LEEUW, ERIK · 2011 to 2012
$422k
NIAID NIH HHS AI092033NIAID NIH HHS R21 AI092033
6 · The paper itself

Abstract

We have recently identified low-molecular weight compounds that act as inhibitors of Lipid II, an essential precursor of bacterial cell wall biosynthesis. Lipid II comprises specialized lipid (bactoprenol) linked to a hydrophilic head group consisting of a peptidoglycan subunit (N-acetyl glucosamine [GlcNAc]-N-acetyl muramic acid [MurNAc] disaccharide coupled to a short pentapeptide moiety) via a pyrophosphate. One of our lead compounds, a diphenyl-trimethyl indolene pyrylium, termed BAS00127538, interacts with the MurNAc moiety and the isoprenyl tail of Lipid II. Here, we report on the structure-activity relationship of BAS00127538 derivatives obtained by in silico analyses and de novo chemical synthesis. Our results indicate that Lipid II binding and bacterial killing are related to three features: the diphenyl moiety, the indolene moiety, and the positive charge of the pyrylium. Replacement of the pyrylium moiety with an N-methyl pyridinium, which may have importance in stability of the molecule, did not alter Lipid II binding or antibacterial potency.

Indexed as

Anti-Bacterial AgentsBacteriaCell LineCell SurvivalDrug DesignHumansIndolesMicrobial Sensitivity TestsPyransSmall Molecule LibrariesStructure-Activity RelationshipUridine Diphosphate N-Acetylmuramic AcidAnti-Bacterial AgentsBAS00127538Indolesmuramyl-NAc-(pentapeptide)pyrophosphoryl-undecaprenolPyransSmall Molecule LibrariesUridine Diphosphate N-Acetylmuramic Acidantibioticscomputer-aided drug designLipid IIphospholipid

Identifiers

PMID25987836
PMCPMC4422293
OpenAlexW2118596329

What OpenQuestion holds

Textmetadata
LicenceCC BY-NC
Read underepoch 390

Registered trials

None linked

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.