ABSTRACT
Anoplin (GLLKRIKTLL-NH2) is of current interest due to its short sequence and specificity towards bacteria. Recent studies on anoplin have shown that truncation and acylation compromises its antimicrobial activity and specificity, respectively. In this study, truncated analogues (pal-ano-9 to pal-ano-5) of palmitoylated anoplin (pal-anoplin) were synthesized to determine the effects of C-truncation on its bioactivities. Moreover, secondary structure of each analogue using circular dichroism (CD) spectroscopy was determined to correlate with bioactivities. Interestingly, pal-anoplin, pal-ano-9 and pal-ano-6 were helical in water, unlike anoplin. In contrast, pal-ano-8, pal-ano-7 and pal-ano-5, with polar amino acid residues at the C-terminus, were random coil in water. Nevertheless, all the peptides folded into helical structures in 30% trifluoroethanol/water (TFE/H2O) except for the shortest analogue pal-ano-5. Hydrophobicity played a significant role in the enhancement of activity against bacteria E. coli and S. aureus as all lipopeptides including the random coil pal-ano-5 were more active than the parent anoplin. Meanwhile, the greatest improvement in activity against the fungus C. albicans was observed for pal-anoplin analogues (pal-ano-9 and pal-ano-6) that were helical in water. Although, hydrophobicity is a major factor in the secondary structure and antimicrobial activity, it appears that the nature of amino acids at the C-terminus also influence folding of lipopeptides in water and its antifungal activity. Moreover, the hemolytic activity of the analogues was found to correlate with hydrophobicity, except for the least hemolytic, pal-ano-5. Since most of the analogues are more potent and shorter than anoplin, they are promising drug candidates for further development.
Subject(s)
Antifungal Agents/chemistry , Antifungal Agents/pharmacology , Antimicrobial Cationic Peptides/chemistry , Antimicrobial Cationic Peptides/pharmacology , Wasp Venoms/chemistry , Wasp Venoms/pharmacology , Circular Dichroism , Escherichia coli/drug effects , Lipoylation , Microbial Sensitivity Tests , Protein Structure, Secondary , Staphylococcus aureus/drug effectsABSTRACT
A new nasal mask for nocturnal, intermittent positive pressure ventilation was used by patients with symptomatic sleep hypoventilation due to chronic neuromuscular disorders. The custom-fabricated mask is cast in visible light curing acrylic from a plaster model. Air is delivered through plastic tubes cast in the mask. The treatment was introduced through close cooperation between a physiotherapist and a technician. Evaluation was performed after 4-34 months' regular use. The mask was well tolerated. All patients reported comfortable sleep and symptom relief. The effectiveness was confirmed by whole-night measurements of oxygen saturation and end-tidal carbon dioxide.
