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Lipidated α-peptide/β-peptoid hybrids with potent anti-inflammatory activity
- Source :
- Journal of medicinal chemistry. 58(2)
- Publication Year :
- 2014
-
Abstract
- In this study, we investigated, optimized, and characterized a novel subclass of host defense peptide (HDP) mimics based on α-peptide/β-peptoid hybrid oligomers with an alternating cationic/hydrophobic design with respect to their ability to modulate the pro-inflammatory response by human primary leukocytes upon exposure to bacterial components. Structure-activity studies revealed that certain lipidated α-peptide/β-peptoid hybrid oligomers possess anti-inflammatory activities in the submicromolar range with low cytotoxicity, and that the anti-inflammatory activity of the HDP mimics is dependent on the length and position of the lipid element(s). The resulting lead compound, Pam-(Lys-βNSpe)6-NH2, blocks LPS-induced cytokine secretion with a potency comparable to that of polymyxin B. The mode of action of this HDP mimic appears not to involve direct LPS interaction since it, in contrast to polymyxin B, displayed only minor activity in the Limulus amebocyte lysate assay. Flow cytometry data showed specific interaction of a fluorophore-labeled lipidated α-peptide/β-peptoid hybrid with monocytes and granulocytes indicating a cellular target expressed by these leukocyte subsets.
- Subjects :
- Lipopolysaccharides
medicine.drug_class
Polymyxin
Anti-Inflammatory Agents
Peptide
Flow cytometry
chemistry.chemical_compound
Peptoids
Structure-Activity Relationship
Drug Discovery
medicine
Immunologic Factors
Cytotoxicity
chemistry.chemical_classification
medicine.diagnostic_test
Interleukin-6
Tumor Necrosis Factor-alpha
Peptoid
chemistry
Biochemistry
Limulus amebocyte lysate
Molecular Medicine
Cytokine secretion
Peptidomimetics
Polymyxin B
medicine.drug
Subjects
Details
- ISSN :
- 15204804
- Volume :
- 58
- Issue :
- 2
- Database :
- OpenAIRE
- Journal :
- Journal of medicinal chemistry
- Accession number :
- edsair.doi.dedup.....7272621ab34964b26d386d1de04eb4d1