Improved proteolytic stability of chicken cathelicidin-2 derived peptides by D-amino acid substitutions and cyclization

Autor: Edwin J.A. Veldhuizen, E.M. Molhoek, A. van Dijk, Henk P. Haagsman, Floris J. Bikker
Přispěvatelé: Oral Biochemistry, Orale Biochemie (OII, ACTA), Strategic Infection Biology, LS Moleculaire Afweer, I&I SIB3
Jazyk: angličtina
Rok vydání: 2011
Předmět:
Lipopolysaccharides
Amino acid substitution
Unclassified drug
Physiology
Cytotoxicity
medicine.medical_treatment
Peptide
Proteinase
Biochemistry
Cathelicidin
Bacterial protein
Bacterium lipopolysaccharide
chemistry.chemical_compound
Endocrinology
Drug Stability
Life
Protein stability
Peptide synthesis
Bacteria (microorganisms)
Cells
Cultured
Chromatography
High Pressure Liquid
Priority journal
chemistry.chemical_classification
medicine.diagnostic_test
Tryptophan
Trypsin
Anti-Bacterial Agents
Protein modification
d-Amino acid substitution
EELS - Earth
Environmental and Life Sciences
Antibacterial activity
Stability
Human
medicine.drug
Staphylococcus aureus
Stereochemistry
Phenylalanine
Proteolysis
Protein variant
Enzyme-Linked Immunosorbent Assay
Cathelicidin 2
Microbial Sensitivity Tests
Bactericidal activity
Protein degradation
Biology
Article
Cellular and Molecular Neuroscience
SDG 3 - Good Health and Well-being
medicine
Animals
Humans
Interleukin-6
CBRN - CBRN Protection
Chicken cathelicidin-2
Peripheral blood mononuclear cell
Nonhuman
Human cell
chemistry
Cyclization
Host defense peptide
Protein engineering
Peptides
Chickens
Controlled study
Antimicrobial Cationic Peptides
Zdroj: Peptides, 32(5), 875-880. Elsevier Inc.
Peptides, 32(5), 875-880. Elsevier
Peptides, 5, 32, 875-880
Molhoek, E M, van Dijk, A, Veldhuizen, E J A, Haagsman, H P & Bikker, F J 2011, ' Improved proteolytic stability of chicken cathelicidin-2 derived peptides by D-amino acid substitutions and cyclization ', Peptides, vol. 32, no. 5, pp. 875-880 . https://doi.org/10.1016/j.peptides.2011.02.017
ISSN: 0196-9781
DOI: 10.1016/j.peptides.2011.02.017
Popis: A truncated version of host defense peptide chicken cathelicidin-2, C1-15, possesses potent, broad spectrum antibacterial activity. A variant of this peptide, F2,5,12W, which contains 3 phenylalanine to tryptophan substitutions, possesses improved antibacterial activity and lipopolysaccharide (LPS) neutralizing activity compared to C1-15. In order to improve the proteolytic resistance of both peptides we engineered novel chicken cathelicidin-2 analogs by substitution of l- with d-amino acids and head-to-tail cyclization. Both cyclic and d-amino acid variants showed enhanced stability in human serum compared to C1-15 and F2,5,12W. The d-amino acid variants were fully resistant to proteolysis by trypsin and bacterial proteases. Head-to-tail cyclization of peptide F2,5,12W resulted in a 3.5-fold lower cytotoxicity toward peripheral blood mononuclear cells. In general, these modifications did not influence antibacterial and LPS neutralization activities. It is concluded that for the development of novel therapeutic compounds based on chicken cathelicidin-2 d-amino acid substitutions and cyclization must be considered. These modifications increase the stability and lower cytotoxicity of the peptides without altering their antimicrobial potency. © 2011 Elsevier Inc. All rights reserved.
Databáze: OpenAIRE
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