Many Gram-negative bacteria have become multi-drug resistant in recent years, as they have developed mechanisms to escape the therapeutic effects of current antibiotic drugs. New antibiotics against drug resistant bacteria are thus urgently needed as the current arsenal of drugs becomes ineffective against such resistant pathogens. Many research groups are trying different approaches, but now Polyphor Ltd., has come up with an interesting finding, they have discovered a new class of antibiotics with a novel mode of action (Science 19 February 2010: Vol. 327. no. 5968, pp. 1010 - 1013). As per the claim by the lead researcher, Prof. John Robinson at the University of Zürich (in collaboration with Polyphor Ltd.,) the new class of antibiotics is effective against multi-drug resistant Gram-negative bacteria, opening up new treatment options for serious and often life-threatening infections. The most advanced drug candidate in this new class, POL7080, selectively kills the dangerous bacteria Pseudomonas aeruginosa.
Polyphor applied its proprietary Protein Epitope Mimetics Technology (PEM Technology) to identify new antibiotics that either act against a broad-spectrum of bacteria or selectively target one particular bacterial strain. This joint research effort resulted in the discovery of a new drug target and mechanism of action by which Gram-negative bacterii are killed effectively.
About Protein Epitope Mimetics (PEM Technology) :
Using a biologically relevant peptide or protein structure as a starting point for lead identification represents one of the most powerful approaches in modern drug discovery. In protein epitope mimetic (PEM) approach, where folded 3D structures of peptides and proteins are taken as starting points for the design of synthetic molecules that mimic key epitopes involved in protein–protein and protein–nucleic acid interactions. By transferring the epitope from a recombinant to a synthetic scaffold that can be produced by parallel combinatorial methods, it is possible to optimize target affinity and specificity as well as other drug-like ADMET properties (Absorption, Distribution, Metabolism, Excretion and Toxicity (ADMET) properties by Quantitative Structure-Activity Relationships, QSAR). The PEM technology is a powerful tool for target validation, and for the development of novel PEM-based drugs.
As per the claim by the lead researcher Prof. J. A. Robinson, one major target recently has been the development of PEMs with antibiotic activity against Gram negative bacteria, in particular, Pseudomonas aeruginosa. Antibiotics with new mechanisms of action are urgently required to combat the growing health threat posed by resistant pathogenic microorganisms.
Researchers, synthesized a family of peptidomimetic antibiotics (fully synthetic, medium-size cyclo peptide-like molecules), based on the antimicrobial peptide protein I. Several rounds of optimization gave a lead compound that was active in the nanomolar range against gram-negative Pseudomonas sp.,
Researchers conclude that, the leading antibiotic PEMdrug candidate POL7080 represents an important new weapon to combat life threatening infections with Pseudomonas aeruginosa which frequently occur in the hospital setting or in chronic lung infections.
Polyphor is currently preparing the start of Phase I clinical trials with POL7080 to rapidly advance the clinical development and has initiated out-licensing negotiations with Pharma partners. The company is optimistic about the positive clinical results and there by making way for this new class of antibiotics...
Ref : http://www.polyphor.com/PolyphorInhalt/Infogate/PressReleases/PressRelease20100219_en.pdf
