Direct affinity screening chromatography-mass spectrometry assay for identification of antibacterial agents from natural product sources.
A direct affinity screening-mass spectrometry assay, coupled to liquid chromatography, is presented as a tool for natural product drug discovery. Using the assay, fractionated extracts from a Caribbean gorgonian coral were shown to contain a new chemical entity (NCE) which binds to a mimic of the Gram positive bacterial cell wall (lysine-D-alanine-D-alanine). Conditions for observation of a specific noncovalent complex between the NCE and the target mimic using electrospray ionization-mass spectrometry were validated in a series of positive and negative control experiments, which featured flow injection analysis-based titrations. While the structural identity of the NCE could not be determined due to limited sample quantities, this work provides proof-of-principle for such an approach to potentially accelerate drug discovery from natural product sources.
Department of Chemistry and Biochemistry, The University of Texas at Arlington, Arlington, TX, USA. kschug@uta.edu
Kevin A
KA
Schug
Evelyn
E
Wang
Sijia
S
Shen
Sunaina
S
Rao
Stephanie M
SM
Smith
Laura
L
Hunt
Laura D
LD
Mydlarz
D000409:Alanine / Q000737:chemistry*; D000818:Animals; D037421:Anthozoa / Q000737:chemistry; D000900:Anti-Bacterial Agents / Q000032:analysis* / Q000302:isolation & purification; D001688:Biological Products / Q000737:chemistry*; D002846:Chromatography, Affinity; D006094:Gram-Positive Bacteria / Q000187:drug effects; D008239:Lysine / Q000737:chemistry*; D009842:Oligopeptides / Q000032:analysis* / Q000302:isolation & purification; D021241:Spectrometry, Mass, Electrospray Ionization
D000900:Anti-Bacterial Agents; D001688:Biological Products; D009842:Oligopeptides; D008239:Lysine; D000409:Alanine