Journal of Bacteriology & Parasitology

Development of novel antimicrobial lipopeptides against MDR Gram-negative â??superbugsâ??

3^rd International Congress on Bacteriology and Infectious Diseases

August 04-06, 2015 Valencia, Spain

Tony Velkov

Scientific Tracks Abstracts: J Bacteriol Parasitol

Abstract:

The octapeptins are a family of naturally occurring cyclic lipopeptide antibiotics with a broad antimicrobial spectrum against
multidrug-resistant (MDR) Gram-negative and Gram-positive ‘superbugs’. Octapeptins were discovered over 30 years ago,
consequently there is limited information on their chemical biology and structure-activity-relationships (SAR). Accordingly,
the broad aim of our study is to explore the chemical biology of the octapeptins through a SAR approach. Synthetic chemistry
will be employed to generate a large series of novel analogs that will be evaluated against the biological systems the octapeptins
are known to modulate. The best approach to achieve this is through the substitution of existing amino acids with novel
derivatives rather than chemical modification of the side-chain functionalities. This can only be achieved through a ‘total
synthesis’ approach which is a particularly challenging task considering the complex chemical structure of the octapeptins. To
the best of our knowledge, we are the first group to have developed an efficient routine ‘total synthesis’ of octapeptins on a scale
that would allow for mechanistic investigations of antibacterial activity and resistance. For the first time our novel approach
will interface the chemistry and biology of these important antibiotic compounds to investigate the underlying SAR with the
purpose of creating new functions. More specifically the ultimate aim is to med-chem out liabilities such as nephrotoxicity
whilst concomitantly improving the antimicrobial activity and spectrum, thereby creating the foundations for a new generation
of safer and more efficacious antibiotics.

Biography :

Tony Velkov completed PhD in 2000 from Monash University. His anti-infective discovery research is at the leading edge globally. He was awarded a NHMRC
Research Fellowships in 2006, 2011 and 2014. The quality and impact of his independent research was recognized by the NHMRC with an Excellence Award
in 2011. He has published over 50 papers in high-caliber journals, 3 book chapters and 15 conference presentations. The dynamic team he leads consists of 3
postdocs, 3 RAs and 9 PhD students. Over the last 6 years, he has obtained >$9M funding from the NIH, NHMRC and foundations.