effects of d-lysine substitutions on the activity and selectivity of antimicrobial peptide cm15影响d-lysine替换cm15抗菌肽的活性和选择性.pdfVIP

Polymers 2011, 3, 2088-2106; doi:10.3390/polym3042088 OPEN ACCESS polymers ISSN 2073-4360 /journal/polymers Article Effects of D-Lysine Substitutions on the Activity and Selectivity of Antimicrobial Peptide CM15 Heather M. Kaminski and Jimmy B. Feix * Department of Biophysics, Medical College of Wisconsin, 8701 Watertown Plank Rd., Milwaukee, WI 53226, USA; E-Mail: hkaminski@ * Author to whom correspondence should be addressed; E-Mail: jfeix@; Tel.: +1-414-456-4037. Received: 7 October 2011; in revised form: 9 November 2011 / Accepted: 28 November 2011 / Published: 6 December 2011 Abstract: Despite their potent antimicrobial activity, the usefulness of antimicrobial peptides (AMPs) as antibiotics has been limited by their toxicity to eukaryotic cells and a lack of stability in vivo. In the present study we examined the effects of introducing D-lysine residues into a 15-residue hybrid AMP containing residues 1–7 of cecropin A and residues 2–9 of melittin (designated CM15). Diastereomeric analogs of CM15 containing between two and five D-lysine substitutions were evaluated for their antimicrobial activity, lysis of human erythrocytes, toxicity to murine macrophages, ability to disrupt cell membranes, and protease stability. All of the analogs caused rapid permeabilization of the Staphylococcus aureus cell envelope, as indicated by uptake of SYTOX green. Permeabilization of the plasma membrane of RAW264.7 macrophages was also observed