Abstract
Esculentin-2EM is a 37-residue, cationic, amphipathic, α-helical antimicrobial peptide isolated from a Korean frog, Glandirama emeljanovi. Many studies revealed that truncation of this peptide results in substantial decreases in its antimicrobial activity. Lee and his colleagues have recently reported that a 23-residue esculentin-2EM analog containing a tryptophanyl substitution at position 16 showed a significant recovery of the antimicrobial activity of the parent peptide. Here we report a new series of 15-residue esculentin-2EM analogs which are constrained into an α-helical conformation via an oct-4-enyl cross-link. The resulting 'stapled' derivatives displayed remarkable increases not only in antimicrobial activity but also in helical content and protease resistance compared to Lee's original 23-residue esculentin-2EM analog. The preliminary data obtained in this work strongly supports the potential of our strategy for the development of a new class of peptide antibiotics.
Original language | English |
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Pages (from-to) | 6717-6720 |
Number of pages | 4 |
Journal | Bioorganic and Medicinal Chemistry Letters |
Volume | 23 |
Issue number | 24 |
DOIs | |
State | Published - 15 Dec 2013 |
Keywords
- Antimicrobial peptides
- Esculentin-2EM
- Proteolytic resistance
- Stapled peptides
- α-Helix