Antimicrobial Agents for the Treatment of Multidrug-Resistant Bacteria Infections
- 详细技术说明
- The invention provides synthetic compounds, methods ofuse, and strategies to design novel compounds that are bacteria-specific andresistant to protease activity.
- *Abstract
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Theemergence of multidrug-resistant (MDR) bacteria causes a growing problemworldwide, particularly in the hospital setting where nosocomial infections affect5 to 10% of patients per year.
A team at Cornell looked at alternatives totraditional antibiotics and developed a rapidand efficient approach for the assembly of synthetic sequence-definedoliothioetheramides (oligoTEAs) that mimic properties and antibacterialactivities of antimicrobial peptides (AMPs) bytuning molecule hydrophobicity and charge.
Using this approach, the team synthetized novel antimicrobialagents then designed strategies to render their novel compounds active in specificbacterial cells as well as to resist to bacterial proteases. Proteases are known to participate in theregulation of resistance to antimicrobials.
So far, the teamhas identified four promising compounds that have been the tested in vitro on MRSA, A. baumannii, K. pneumonia, B. subtilis, E.coli, and USA300 strains and in vivo on mice infected by MRSAstrains. The resulting minimum inhibitory concentration (MIC) of each compoundshad ranged from 0.5-2 µg/ml. Moreover, these compounds have showedlittle cytotoxicity.
These compoundscan be a good alternative to other compounds that may induce a high incidenceof nephrotoxicity in the treatment of MDR Gram-negative bacteria. Studies are continuing.
PotentialApplications
Therapeuticoptions against multidrug-resistant pathogens.
Advantages
- New class of sequence-defined antimicrobial agents
- Selectively kills bacterial cells over mammalian cells
- Can be designed to be narrow-spectrum compounds.
- *Licensing
- Jeff Fearnjcf55@cornell.edu607-254-4502
- 其他
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- Mintu Porel, et al. (2017). Sequence-Defined BackboneModifications Regulate Antibacterial. ACS Chem. Biol. 2017, 12,715−723
- Mintu Porel and Christopher A. Alabi. (2014). Sequence-DefinedPolymers via Orthogonal Allyl Acrylamide Building Blocks. J. Am. Chem. Soc. 2014,136, 13162−13165
- Related invention: D-6762 “Method for Synthesisof End-functional Sequence-Controlled Polymers”.
- 国家/地区
- 美国
