Selective toxin sequestrants for the treatment of bacterial infections.
Bacterial toxin-mediated diarrheal disease is a major cause of morbidity and mortality worldwide. In this work we designed an on-bead library of protease-resistant, acid-stable peptoid molecules and screened for high affinity binding of cholera toxin. From 100 000 compounds, we discovered a single sequence of residues that can bind and retain cholera toxin at high affinity when immobilized on a solid-phase particle. Furthermore, we demonstrate that these peptoid-displaying particles can sequester active cholera toxin from cell culture media sufficient to protect intestinal cells. We foresee this work as contributory to a potential adjunct therapeutic strategy against cholera infections and other toxin-mediated diseases.
Division of Translational Research, Departments of Internal Medicine, University of Texas Southwestern Medical Center, 5323 Harry Hines Boulevard, Dallas, Texas 75390-9185, USA.
Levi S
LS
Simpson
Lyle
L
Burdine
Amal K
AK
Dutta
Andrew P
AP
Feranchak
Thomas
T
Kodadek
D001424:Bacterial Infections / Q000188:drug therapy; D001426:Bacterial Proteins / Q000378:metabolism*; D002460:Cell Line; D002772:Cholera Toxin / Q000737:chemistry / Q000378:metabolism*; D004926:Escherichia coli / Q000201:enzymology; D006801:Humans; D007413:Intestinal Mucosa / Q000166:cytology / Q000187:drug effects* / Q000382:microbiology*; D008024:Ligands; D019151:Peptide Library; D010455:Peptides / Q000737:chemistry / Q000378:metabolism* / Q000494:pharmacology*; D011485:Protein Binding; D021122:Protein Subunits / Q000737:chemistry / Q000378:metabolism
D001426:Bacterial Proteins; D008024:Ligands; D019151:Peptide Library; D010455:Peptides; D021122:Protein Subunits; D002772:Cholera Toxin