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Biological results:By varying the lipophilic side-chains of the beta 2,2 -amino acids, we obtained a series ofhighly potent beta-peptidomimetics with MIC values of 2.1-7.2 μM against MRSA, MRSE,S. aureus and E. coli [7]. The results from screening of antimicrobial activity showedfurthermore that the beta-peptidomimetics were in general more potent against the Grampositivebacteria than against E. coli. There was also a strong correlation betweenantimicrobial potency of the compounds and overall lipophilicity measured on a RP-HPLCsystem [7]. The beta-peptidomimetics displayed very low hemolytic activity, with EC 20values well above their MIC values. Plating of treated bacterium suspensions showed thatthe beta-peptidomimetics were bactericidal. The bactericidal effect correlated with bothincreased concentration and increased time of treatment.ConclusionIn the current study we chose to investigate a scaffold that would fulfill the pharmacophoremodel of short AMP’s. The resulting peptidomimetics were bioisosteres of di-peptides buthaving the side-chain functionalities of tri-peptides due to the beta 2,2 -amino acidderivatives. The small size of the beta-peptidomimetics may provide solutions to manycommon problems associated with developing AMP’s into novel antimicrobial agents. Thestudy has demonstrated that small beta-peptidomimetics can be used to mimic theantimicrobial potency and selectivity of much larger AMP’s, and that such smallamphipathic scaffolds may be promising drug-candidates for treatment of serious bacterialinfections.References1. Projan, S.J. Drug Discov. Today 13, 279-280 (2008).2. Boucher, H.W., et al. Clinical Infectious Diseases 48, 1-12 (2009).3. Hancock, R.E. Microbiology 149, 3343-3345 (2003).4. Giuliani, A., et al. Central Eur. J. Biol. 2, 1-33 (2007).5. Boman, H.G. J. Intern. Med. 254, 197-215 (2003).6. Strøm, M.B., et al. J. Med. Chem. 46, 1567-1570 (2003).7. Hansen, T., et al. J. Med. Chem. 53, 595-606 (2010).265