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Researchers in Japan have identified multiple promising new drug candidates to treat antibiotic-resistant infections, including the superbug MRSA (methicillin-resistant Staphylococcus aureus). The team developed a new technique to enhance the infection-fighting potential of natural chemicals and test them quickly.
In laboratory tests, three of the synthetic molecules that the researchers built are four times more effective at killing bacteria than their natural predecessor, which is itself already an order of magnitude more potent than the current drug used against MRSA, vancomycin.
Technique - Thousands - Molecules - Synthesis - Assistant
"Our technique is fast because we can build thousands of new molecules in a single synthesis," said Assistant Professor Hiroaki Itoh from the University of Tokyo Department of Pharmaceutical Sciences.
Researchers first identified the promising new natural antibiotic from a soil sample collected in the subtropical island of Okinawa in southwestern Japan. The antibiotic, called lysocin E, has a unique mechanism of killing bacteria compared to the currently available classes of antibiotics. Even MRSA would be defenseless against it.
Lysocin - E - Chemical - Structure - Ring
Lysocin E has a complex chemical structure that resembles a tambourine: a large ring with 12 short side chains.
The protein building blocks, called amino acids, which form those chains, each contribute to the overall function of the entire molecule. Swapping the naturally occurring amino acids for different ones could enhance the function of the antibiotic.
Improvements - Selection - Itoh
"We try to find the improvements that natural selection did not make yet," said Itoh.
Researchers focused on four side chains and tested how seven different amino acids might enhance lysocin E's antibacterial activity. All possible combinations of the four side chains and seven amino acids meant that researchers needed to build 2,401 different synthetic versions of modified lysocin E.
Researchers - Lysocin
Researchers built all 2,401 modified lysocin...
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