The synthetic compounds are as effective against MSRA.

The recently discovered compound teixobactin has shown real promise as a potential new antibiotic agent, with the ability to kill many bacteria that have developed a resistance to available antibiotic treatments. Many believe this compound, if proven both safe and effective, could be the first new antibiotic approved in 30 years – but it must be practically producible on a commercial scale.

Teixobactin is a highly complex molecule that poses synthetic difficulties, however. Researchers at the University of Lincoln, UK may have found a way around the problem. The scientists report developing practical synthetic routes to two molecules  that are simplified versions of teixobactin yet retain the antibiotic effectiveness of the natural product.

It has been thought that to maintain effectiveness, simpler versions of teixobactin had to contain positively charged (cationic) amino acids in a side chain in a specific location in the teixobactin structure in order for proper binding to bacteria to occur. The cationic amino acid found in teixobactin is the rare amino acid enduracididine, which is difficult to synthesize.

The University of Lincoln researchers have shown, however, that simpler derivatives of teixobactin incorporating amino acids that are not positively charged, and thus do not have what was thought to be binding capability, at the relevant position exhibit identical potency to that of teixobactin.

The synthesis of teixobactin derivatives containing these alternative, non-cationic amino acids requires one key coupling step that is often complete in 10 minutes – compared to 30 hours for preparation of teixobactin

“When teixobactin was discovered it was ground breaking in itself as a new antibiotic which kills bacteria without detectable resistance including superbugs such as MRSA,” leading researcher Dr. Ishwar Singh, a specialist in novel drug design and development from the University of Lincoln’s School of Pharmacy.  “This simplified design and more efficient synthesis will enable work to be carried out at a commercial level. Enduracididine was severely limiting our ability to do this because of its scarcity, a complex multistep synthesis and long and repetitive steps of between 16 and 30 hours with high failure rate and very low yields.”

Singh added that: “We needed to make a change to the structure so that we could make the molecule more viable for drug development. We had tried replacing it with other amino acids with a similar make up, but they all were less potent in comparison to the natural form of teixobactin. Now, we have discovered that we can, in fact, use amino acids, which are structurally different and are commercially-available.”

The two new compounds have been shown to be 16 times more potent than a clinically-used antibiotic in killing the superbug MRSA. They are also highly potent against other antibiotic-resistant infections, such as vancomycin-resistant enterococci and tuberculosis, according to Singh.

Singh is currently working with colleagues from the School of Life Sciences and the School of Chemistry at the University of Lincoln to develop teixobactin derivatives that are suitable for formulation into viable drugs.