title: Targeting bacteria via iminoboronate chemistry of amine-presenting lipids.
abstract: Synthetic molecules that target specific lipids serve as powerful tools for understanding membrane biology and may also enable new applications in biotechnology and medicine. For example, selective recognition of bacterial lipids may give rise to novel antibiotics, as well as diagnostic methods for bacterial infection. Currently known lipid-binding molecules primarily rely on noncovalent interactions to achieve lipid selectivity. Here we show that targeted recognition of lipids can be realized by selectively modifying the lipid of interest via covalent bond formation. Specifically, we report an unnatural amino acid that preferentially labels amine-presenting lipids via iminoboronate formation under physiological conditions. By targeting phosphatidylethanolamine and lysylphosphatidylglycerol, the two lipids enriched on bacterial cell surfaces, the iminoboronate chemistry allows potent labelling of Gram-positive bacteria even in the presence of 10% serum, while bypassing mammalian cells and Gram-negative bacteria. The covalent strategy for lipid recognition should be extendable to other important membrane lipids.
authors.affiliation: Department of Chemistry, Merkert Chemistry Center, Boston College, 2609 Beacon Street, Chestnut Hill, Massachuetts 02467, USA.
authors.forename: Anupam
authors.initials: A
authors.lastname: Bandyopadhyay
authors.affiliation: Department of Chemistry, Merkert Chemistry Center, Boston College, 2609 Beacon Street, Chestnut Hill, Massachuetts 02467, USA.
authors.forename: Kelly A
authors.initials: KA
authors.lastname: McCarthy
authors.affiliation: Department of Chemistry, Merkert Chemistry Center, Boston College, 2609 Beacon Street, Chestnut Hill, Massachuetts 02467, USA.
authors.forename: Michael A
authors.initials: MA
authors.lastname: Kelly
authors.affiliation: Department of Chemistry, Merkert Chemistry Center, Boston College, 2609 Beacon Street, Chestnut Hill, Massachuetts 02467, USA.
authors.forename: Jianmin
authors.initials: J
authors.lastname: Gao
mesh_terms: D000588:Amines / Q000737:chemistry*; D000900:Anti-Bacterial Agents / Q000737:chemistry*; D001412:Bacillus subtilis; D001709:Biotechnology / Q000639:trends; D001896:Boron Compounds / Q000737:chemistry*; D018920:Coculture Techniques; D004305:Dose-Response Relationship, Drug; D004926:Escherichia coli / Q000378:metabolism; D006801:Humans; D019169:Jurkat Cells; D008055:Lipids / Q000737:chemistry*; D008239:Lysine / Q000737:chemistry; D009682:Magnetic Resonance Spectroscopy; D013058:Mass Spectrometry; D008563:Membrane Lipids / Q000378:metabolism; D018613:Microscopy, Confocal; D010713:Phosphatidylcholines / Q000737:chemistry; D010714:Phosphatidylethanolamines / Q000737:chemistry; D010715:Phosphatidylglycerols / Q000737:chemistry; D010718:Phosphatidylserines / Q000737:chemistry; D013109:Sphingomyelins / Q000737:chemistry
chemical_list: D000588:Amines; D000900:Anti-Bacterial Agents; D001896:Boron Compounds; D008055:Lipids; D008563:Membrane Lipids; D010713:Phosphatidylcholines; D010714:Phosphatidylethanolamines; D010715:Phosphatidylglycerols; D010718:Phosphatidylserines; D013109:Sphingomyelins; C483858:phosphatidylethanolamine; C002285:lysylphosphatidylglycerol; D008239:Lysine