Abstract
The emergence of multidrug-resistant strains of Acinetobacter baumannii (MDRAB) constitutes a serious threat to public health and necessitates the discovery of new types of antimicrobial agents. Alyteserin-1c (GLKEIFKAGLGSLVKGIAAHVAS·NH 2) is a cationic, α-helical peptide that was first isolated from skin secretions of the midwife toad Alytes obstetricans. Synthetic alyteserin-1c displayed potent activity against clinical isolates of MDRAB (minimum inhibitory concentration, MIC = 5–10 μM; minimum bactericidal concentration, MBC = 5–10 μM) while displaying low hemolytic activity against human erythrocytes (LD 50 = 220 μM). Increasing the cationicity of alyteserin-1c by the substitution Glu 4 → Lys enhanced the potency against MDRAB (MIC = 1.25–5 μM; MBC = 1.25–5 μM) as well as decreasing hemolytic activity (HC 50 > 400 μM). More than 99.9% of the bacteria were killed within 30 min by the [E4K] analog at a concentration of 1 × MBC. Increasing the cationicity of [E4K]alyteserin-1c further by the additional substitutions of Ala 8,Val 14 or Ala 18 by l-Lys did not enhance antimicrobial potency. Derivatives of [E4K]alyteserin-1c containing a palmitate group coupled either to α-amino group at the N-terminus or to ɛ-amino group on the Lys 18 residue of the [E4K,A18K] analog retained antimicrobial activity but showed dramatically increased hemolytic activities (>40- and >13-fold, respectively).
Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
