Document Detail


Structural studies of a peptide with immune modulating and direct antimicrobial activity.
MedLine Citation:
PMID:  20851346     Owner:  NLM     Status:  MEDLINE    
Abstract/OtherAbstract:
The structure and function of the synthetic innate defense regulator peptide 1018 was investigated. This 12 residue synthetic peptide derived by substantial modification of the bovine cathelicidin bactenecin has enhanced innate immune regulatory and moderate direct antibacterial activities. The solution state NMR structure of 1018 in zwitterionic dodecyl phosphocholine (DPC) micelles indicated an α-helical conformation, while secondary structures, based on circular dichroism measurements, in anionic sodium dodecyl sulfate (SDS) and phospholipid vesicles (POPC/PG in a 1:1 molar ratio) and simulations revealed that 1018 can adopt a variety of folds, tailored to its different functions. The structural data are discussed in light of the ability of 1018 to potently induce chemokine responses, suppress the LPS-induced TNF-α response, and directly kill both Gram-positive and Gram-negative bacteria.
Authors:
Michal Wieczorek; Håvard Jenssen; Jason Kindrachuk; Walter R P Scott; Melissa Elliott; Kai Hilpert; John T J Cheng; Robert E W Hancock; Suzana K Straus
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Chemistry & biology     Volume:  17     ISSN:  1879-1301     ISO Abbreviation:  Chem. Biol.     Publication Date:  2010 Sep 
Date Detail:
Created Date:  2010-09-20     Completed Date:  2011-01-18     Revised Date:  -    
Medline Journal Info:
Nlm Unique ID:  9500160     Medline TA:  Chem Biol     Country:  United States    
Other Details:
Languages:  eng     Pagination:  970-80     Citation Subset:  IM    
Copyright Information:
Copyright © 2010 Elsevier Ltd. All rights reserved.
Affiliation:
Chemistry Department, University of British Columbia, Vancouver, BC, Canada.
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MeSH Terms
Descriptor/Qualifier:
Amino Acid Sequence
Animals
Anti-Bacterial Agents / chemistry*,  pharmacology
Antimicrobial Cationic Peptides / chemistry*,  pharmacology
Cattle
Circular Dichroism
Gram-Negative Bacteria / drug effects
Gram-Positive Bacteria / drug effects
Humans
Immunity, Innate / drug effects
Immunologic Factors / chemistry*,  pharmacology
Micelles
Microbial Sensitivity Tests
Peptides / chemistry*
Peptides, Cyclic / chemistry
Phosphorylcholine / analogs & derivatives,  chemistry
Protein Structure, Secondary
Quantitative Structure-Activity Relationship
Sodium Dodecyl Sulfate / chemistry
Tumor Necrosis Factor-alpha / metabolism
Grant Support
ID/Acronym/Agency:
//Canadian Institutes of Health Research
Chemical
Reg. No./Substance:
0/Anti-Bacterial Agents; 0/Antimicrobial Cationic Peptides; 0/Immunologic Factors; 0/Micelles; 0/Peptides; 0/Peptides, Cyclic; 0/Tumor Necrosis Factor-alpha; 0/innate defense regulating peptide 1018; 107-73-3/Phosphorylcholine; 116229-36-8/bactenecin; 151-21-3/Sodium Dodecyl Sulfate; 53949-18-1/dodecylphosphocholine

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