Also, it is clearly established that the low activity earlier reported for the shorter homologues of chimera 3 (e.g. the 12-mer exhibited almost no activity [23]) may be compensated for by a longer sequence. Chimera 4c corresponds to the analogue where half of the lysines in chimera 3 are replaced by homoarginines, and similarly chimera

4b may be considered an analogue derived from chimera 2 by exchanging half of the homoarginines with lysines. Comparison of the activities found for these two pairs indicates that a high content of homoarginines generally induces a somewhat higher potency; especially, the activity against S. aureus and K. pneumoniae is clearly promoted by a prevalence of guaninido-functionalized residues. A high activity was also found against two isolates of ESBL-producing E. coli (AAS-EC-09 and AAS-EC-010) {Selleck Anti-infection Compound Library|Selleck Antiinfection Compound Library|Selleck Anti-infection Compound Library|Selleck Antiinfection Compound Library|Selleckchem Anti-infection Compound Library|Selleckchem Antiinfection Compound Library|Selleckchem Anti-infection Compound Library|Selleckchem Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|Anti-infection Compound Library|Antiinfection Compound Library|buy Anti-infection Compound Library|Anti-infection Compound Library ic50|Anti-infection Compound Library price|Anti-infection Compound Library cost|Anti-infection Compound Library solubility dmso|Anti-infection Compound Library purchase|Anti-infection Compound Library manufacturer|Anti-infection Compound Library research buy|Anti-infection Compound Library order|Anti-infection Compound Library mouse|Anti-infection Compound Library chemical structure|Anti-infection Compound Library mw|Anti-infection Compound Library molecular weight|Anti-infection Compound Library datasheet|Anti-infection Compound Library supplier|Anti-infection Compound Library in vitro|Anti-infection Compound Library cell line|Anti-infection Compound Library concentration|Anti-infection Compound Library nmr|Anti-infection Compound Library in vivo|Anti-infection Compound Library clinical trial|Anti-infection Compound Library cell assay|Anti-infection Compound Library screening|Anti-infection Compound Library high throughput|buy Antiinfection Compound Library|Antiinfection Compound Library ic50|Antiinfection Compound Library price|Antiinfection Compound Library cost|Antiinfection Compound Library solubility dmso|Antiinfection Compound Library purchase|Antiinfection Compound Library manufacturer|Antiinfection Compound Library research buy|Antiinfection Compound Library order|Antiinfection Compound Library chemical structure|Antiinfection Compound Library datasheet|Antiinfection Compound Library supplier|Antiinfection Compound Library in vitro|Antiinfection Compound Library cell line|Antiinfection Compound Library concentration|Antiinfection Compound Library clinical trial|Antiinfection Compound Library cell assay|Antiinfection Compound Library screening|Antiinfection Compound Library high throughput|Anti-infection Compound high throughput screening| indicating that resistance towards conventional

antibiotics do not affect the sensitivity towards these peptidomimetics, further supporting a different mode of action. Many AMPs exhibit click here a cell envelope-perturbing Temsirolimus in vivo effect [41–43], and hence their target is different from traditional antibiotics of which many act by inhibiting cell wall synthesis or on intracellular targets [44–46]. Notably, S. marcescens was the only bacterial strain that proved tolerant to the peptidomimetics, and thus must harbour specific resistance mechanisms involving induction of changes in the cell envelope. Time-kill experiments showed that S. marcescens was killed more

rapidly than the susceptible strain of S. aureus when treated with chimera 1, 2 or 3 at concentrations close to their MIC values (Figure 2). Polymyxin B and other cationic AMPs may at high doses in themselves act like chelating agents allowing them to penetrate the outer membrane [47, 48], however, a noticeable effect was also seen against S. marcescens at ADAMTS5 concentrations lower that the MIC value (Figure 2C). Rapid killing was also demonstrated for E. coli exposed to the peptidomimetics, indicating that this could be a phenomenon associated with Gram-negative bacteria. Shorter exposure times caused a significant killing of Gram-negative bacteria when treated with some α-helical AMPs that act by permeabilization of the membrane [37]. Another explanation for the observed differences in the rate of killing could be that either the degree or mode of membrane disruption differs among bacteria i.e. the chimeras may exert their effect by a combination of several mechanisms. The fact that cell membranes of different bacteria differs in lipid composition [49] could influence the interaction between phospholipids and AMPs.