By using the type of chemical reaction, MIT researchers have shown that they can change antibiotics so that they can be more effective against drug resistant infections.

Antimicrobial vancomycin chemically linked to antimicrobial peptide, researchers managed to increase the effectiveness of drug resistant bacteria against two strains. Such modification is easy to fulfill the creation of additional combinations of antibiotics and peptide, which researchers said.

"Normally, there would be a lot of steps to get Vancomycin, which would allow us to do something else but we should not take drugs," says Brad Pentuel, MIT's Associate Professor Chemistry and Head of Research. "We will add them together and we will get the reaction of the coniery."

This strategy can also be used to modify other drugs, including cancer drugs. Joining antibodies or other brain proteins of this drug may be easier to use drugs to achieve their goals.

Pentecut Laboratory worked with Stephen Buchwald, Professor of Chemistry at MIT; Scott Miller, professor of chemistry at Yale University; And researchers Visterra, a local biotechnological company, on paper that will show Nov. 5 items Nature is chemistry. The main authors of the article were former MIT postcolonial Daniel Cohen, MIT Post Chi Jang, and MIT's graduate Colin Faden.

Simple reaction

Several years ago, Coen published a discovery that amino acids called selenochecceptin spontaneously reacted to complex compounds without the need for iron catalyst. Cohen concluded that when he combined with mixed electronically defective cellenozininine with antibiotic vancomsin, Selenocycin was given a specific place – electric rings of carbon atoms in vancomycin molecules.

This led researchers to use the use of selenococcase as a "handle" that could be used to connect peptides and small molecular drugs. They were involved in selenosinsinine in natural antimicrobial peptides – small proteins, the majority of which are organisms as part of their immune deficiency. Celenosinsinine, a naturally formed amino acid containing selenium atom, is not as common as other 20 amino acids, but is found in mammalian enzymes in human and other organisms.

Researchers have discovered that these peptides can not connect to vancomycin, but chemical bonds have been consistently in the same place as a result of which all the molecules are identical. Creating such a clean product is difficult to find in the methods of connecting complex molecules. At the same time, such a reaction to the existing methods, presumably, is required from 10 to 15 steps to chemically change vancomycin to make peptide reactions.

"This is the beauty of this method," says rust. "These complex molecules are intensive in areas that can maintain our protein, if protein has a selenosurgery handle that we have developed, it can significantly simplify the process."

The researchers found vancomycin connoisseurs and various antimicrobial peptides (AMPs). They found that one of these molecules, combined with vancomycin and AMP dermacypet, was five times stronger than Vancomycin alone against bacterial strains. Fecalis. Vancomciin, which is associated with AMP's RP-1, has been able to bacterially Baumani, although Vancomitsyn has no effect on this strain. Both strains have high levels of preparations and often cause infections in hospitals.

Modified drugs

This approach should work with peptides for any complex organic molecule that has the right type of electronic rings, researchers say. They had studied about 30 other molecules, including serotonin and resveratrol, and found that they could easily join the phenotype containing selenococcusin. The researchers did not yet realize how these changes could lead to drugs.

In addition, the study of antibiotics, as researchers believe, could use these techniques to create targeted cancer drugs. Scientists may use this approach to antibodies or other proteins to cancer drugs that promote drug use without adverse effects of healthy tissue.

Adding a selenoxurist to a small peptide is a fairly straight process, researchers say they work on the adaptation of the method so that it can be used for larger proteins. They also use experiments to perform this type of conjugation reaction, using the more common amino acids in the cisine, instead of cellenoccceptae.

The survey was funded by the National Institutes of Health, Damon Runyon Cancer Research Foundation Award and Sontag distinguished scientist award.

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