Please use this identifier to cite or link to this item:
doi:10.22028/D291-38089
Title: | Lectin-Targeted Prodrugs Activated by Pseudomonas aeruginosa for Self-Destructive Antibiotic Release |
Author(s): | Meiers, Joscha Rox, Katharina Titz, Alexander |
Language: | English |
Title: | Journal of Medicinal Chemistry |
Volume: | 65 |
Issue: | 20 |
Publisher/Platform: | ACS |
Year of Publication: | 2022 |
Free key words: | Anatomy Antimicrobial agents Conjugate acid-base pairs Peptide and proteins Pharmaceuticals |
DDC notations: | 500 Science |
Publikation type: | Journal Article |
Abstract: | Chronic Pseudomonas aeruginosa infections are characterized by biofilm formation, a major virulence factor of P. aeruginosa and cause of extensive drug resistance. Fluoroquinolones are effective antibiotics but are linked to severe side effects. The two extracellular P. aeruginosa-specific lectins LecA and LecB are key structural biofilm components and can be exploited for targeted drug delivery. In this work, several fluoroquinolones were conjugated to lectin probes by cleavable peptide linkers to yield lectin-targeted prodrugs. Mechanistically, these conjugates therefore remain non-toxic in the systemic distribution and will be activated to kill only once they have accumulated at the infection site. The synthesized prodrugs proved stable in the presence of host blood plasma and liver metabolism but rapidly released the antibiotic cargo in the presence of P. aeruginosa in a self-destructive manner in vitro. Furthermore, the prodrugs showed good absorption, distribution, metabolism, and elimination (ADME) properties and reduced toxicity in vitro, thus establishing the first lectin-targeted antibiotic prodrugs against P. aeruginosa. |
DOI of the first publication: | 10.1021/acs.jmedchem.2c01214 |
URL of the first publication: | https://pubs.acs.org/doi/10.1021/acs.jmedchem.2c01214 |
Link to this record: | urn:nbn:de:bsz:291--ds-380895 hdl:20.500.11880/34405 http://dx.doi.org/10.22028/D291-38089 |
ISSN: | 0022-2623 1520-4804 |
Date of registration: | 18-Nov-2022 |
Description of the related object: | Supporting Information |
Related object: | https://pubs.acs.org/doi/suppl/10.1021/acs.jmedchem.2c01214/suppl_file/jm2c01214_si_001.pdf https://pubs.acs.org/doi/suppl/10.1021/acs.jmedchem.2c01214/suppl_file/jm2c01214_si_002.csv |
Faculty: | NT - Naturwissenschaftlich- Technische Fakultät |
Department: | NT - Chemie |
Professorship: | NT - Univ.-Prof. Dr. phil. Alexander Titz |
Collections: | SciDok - Der Wissenschaftsserver der Universität des Saarlandes |
Files for this record:
File | Description | Size | Format | |
---|---|---|---|---|
acs.jmedchem.2c01214.pdf | 4,25 MB | Adobe PDF | View/Open |
This item is licensed under a Creative Commons License