Design of Novel Amphipathic α-Helical Antimicrobial Peptides with No Toxicity as Therapeutics against the Antibiotic-Resistant Gram-Negative Bacterial Pathogen, Acinetobacter Baumannii

We designed de novo and synthesized two series of five 26-residue amphipathic α-helical cationic antimicrobial peptides (AMPs) with five or six positively charged residues (D-Lys, L-Dab (2,4-diaminobutyric acid) or L-Dap (2,3-diaminopropionic acid)) on the polar face where all other residues are in the D-conformation. Hemolytic activity against human red blood cells was determined using the most stringent conditions for the hemolysis assay, 18h at 37°C, 1% human erythrocytes and peptide concentrations up to 1000 μg/mL (~380 μM). Antimicrobial activity was determined against 7 Acinetobacter baumannii strains, resistant to polymyxin B and colistin (antibiotics of last resort) to show the effect of positively charged residues in two different locations on the polar face (positions 3, 7, 11, 18, 22 and 26 versus positions 3, 7, 14, 15, 22 and 26). All 10 peptides had two D-Lys residues in the center of the non-polar face as “specificity determinants” at positions 13 and 16 which provide specificity for prokaryotic cells over eukaryotic cells. Specificity determinants also maintain excellent antimicrobial activity in the presence of human sera. This study shows that the location and type of positively charged residue (Dab and Dap) on the polar face are critical to obtain the best therapeutic indices.

A Potentially Useful Procedure for Conversion of Ethers to Esters

This communication reports a catalytic system for transformation of ethers into their corresponding esters, especially for cyclic ethers. This efficient procedure was developed as part of our efforts to synthesize nucleoside building blocks and their derivatives. Gas Chromatography-Mass Spectrometry (GC-MS) monitored the reaction processes, Nuclear Magnetic Resonance Spectrometry (NMR), and Infrared Spectrometry (IR) were used to verify the structure of the products. The conversions of Tetrahydrofuran (THF) and other cyclic ether into lactones were accomplished in high yield, over 95%. This approach could be extended too many types of ethers to produce directly corresponding esters simply. Four representatives of ethers were investigated. Cyclic ethers have the higher yields. Linear ethers gave lower yields. The reaction on methoxylcarbon or methyl ether carbon was not observed. The reacted catalyst can be reused over several times. For each reusing, only drops of sulfuric acid need to be added. Nevertheless, the asymmetric ethers selectivity needs to be addressed in future studies.

Assessment of in vitro and in vivo Antimicrobial Activity of an Isonitrosomalononitrile Silver(I) Salt

The design and evaluation of antimicrobial activities of an isonitrosomalononitrile silver(I) salt was reported. This highly stable water-soluble silver salt shows Minimum Inhibitory Concentrations (MIC) values ranging from 0.15 to 5 µg/mL towards both sensitive and resistant Gram-positive and negative bacteria. Furthermore, this silver salt has been investigated for its ability to treat a S. aureus infected Galleria mellonella larvae animal model with promising results. Thus, our results demonstrated that 80% of the treated larvae survived after 24h with respect to 10% of the untreated ones, respectively.