Cai, Xingguang; Capecchi, Alice; Olcay, Başak; Orsi, Markus; Javor, Sacha; Reymond, Jean-Louis (2023). Exploring the Sequence Space of Antimicrobial Peptide Dendrimers. Israel journal of chemistry, 63(10-11) Wiley-VCH 10.1002/ijch.202300096
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There is an urgent need to develop new antibacterial agents against multidrug resistant bacteria. Herein we report our investigation of antimicrobial peptide dendrimers (AMPDs) active against Gram-negative bacteria, whose sequences were designed using a genetic algorithm optimizing molecular similarity to the previously reported AMPD T7 with sequence (KL)8(KKL)4(KKLL)2KKKL. Our computational approach selected analogues unlikely to emerge from a systematic study, including AMPD X66 with a non-conservative Leu→Glu mutation at the dendrimer core which proved compatible with antibacterial effects. Circular dichroism showed that this AMPD is α-helical. Molecular dynamics suggest that its α-helical structure is stabilized by an intramolecular salt bridge involving the core glutamate side chain and a lysine side chain in the dendrimer branches. More substantial variations at the dendrimer core were also tolerated such as the installation of the dianionic pegylated fatty acid side chain of the drug semaglutide potentially useful for in vivo studies.
Item Type: |
Journal Article (Original Article) |
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Division/Institute: |
08 Faculty of Science > Department of Chemistry, Biochemistry and Pharmaceutical Sciences (DCBP) |
UniBE Contributor: |
Cai, Xingguang, Capecchi, Alice, Olcay, Başak, Orsi, Markus, Javor, Sacha, Reymond, Jean-Louis |
Subjects: |
500 Science > 570 Life sciences; biology 500 Science > 540 Chemistry |
ISSN: |
0021-2148 |
Publisher: |
Wiley-VCH |
Language: |
English |
Submitter: |
Sandra Tanja Zbinden Di Biase |
Date Deposited: |
11 Jan 2024 10:23 |
Last Modified: |
11 Jan 2024 10:23 |
Publisher DOI: |
10.1002/ijch.202300096 |
BORIS DOI: |
10.48350/191467 |
URI: |
https://boris.unibe.ch/id/eprint/191467 |
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