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Chemical and metabolic stability of lactoferricin-based cationic antimicrobial tripeptides

Valentijn Vergote UGent, Johan Svenson, Christian Burvenich UGent, Rasmus Karstad and Bart De Spiegeleer UGent (2009) Faculty of Pharmaceutical Sciences 2009 Symposium, Abstracts.
abstract
The widespread overuse and misuse of antibiotics throughout the world has led to bacterial resistance to many commercially available antibiotics. Hence, the development of novel classes of antibiotics is required to address this pressing public health problem. Cationic antimicrobial peptides (CAPs) are considered to be a promising new class of drugs against multi-resistant bacteria [1]. While their minimum antimicrobial motif has been defined [2], the limited success of CAPs so far is partially due to unresolved chemical and metabolic stability issues. In order to obtain comprehensive information regarding the metabolic fate, these peptides and derivatives were tested in vitro by incubation in buffer/denatured plasma, plasma and organ homogenates. A general screening procedure was used [3], where aliquots are withdrawn at pre-determined time points and analyzed by HPLC-UV/PDA-ESI/MS for determination of CAP degradation kinetics and identification of the degradation metabolites. Based on this information, QSPR (Quantitative Structure-Property Relationships) models can be built to predict the stability as a function of the peptide sequence (i.e. which peptide bonds are most unstable). Such a model can then be used to suggest directions for new CAPs with improved pharmaceutical drugability characteristics. References: [1] Svenson J, Stensen W, Brandsdal BO, Haug BE, Monrad J, Svendsen JS. Antimicrobial peptides with stability toward tryptic degradation. Biochemistry 47 (2008) 3777-3788. [2] Strom MB, Haug BE, Skar ML, Stensen W, Stiberg T, Svendsen JS. The pharmacophore of short cationic antibacterial peptides. J Med Chem 46 (2003) 1567-1570. [3] Vergote V, Van Dorpe S, Peremans K, Burvenich C, De Spiegeleer B. In vitro metabolic stability of obestatin: Kinetics and identification of cleavage products. Peptides 29 (2008) 1740-1748.
Please use this url to cite or link to this publication:
author
organization
year
type
conference
publication status
published
subject
keyword
tripeptides, metabolic stability, Cationic antimicrobial peptides, mouse plasma
in
Faculty of Pharmaceutical Sciences 2009 Symposium, Abstracts
conference name
Faculty of Pharmaceutical Sciences 2009 Symposium
conference location
Faculty of Pharmaceutical Sciences, Ghent University
conference start
2009-05-20
conference end
2009-05-20
language
English
UGent publication?
yes
classification
C3
copyright statement
I have retained and own the full copyright for this publication
id
666154
handle
http://hdl.handle.net/1854/LU-666154
date created
2009-05-26 11:53:44
date last changed
2011-07-05 10:24:17
@inproceedings{666154,
  abstract     = {The widespread overuse and misuse of antibiotics throughout the world has led to bacterial resistance to many commercially available antibiotics. Hence, the development of novel classes of antibiotics is required to address this pressing public health problem. Cationic antimicrobial peptides (CAPs) are considered to be a promising new class of drugs against multi-resistant bacteria [1]. While their minimum antimicrobial motif has been defined [2], the limited success of CAPs so far is partially due to unresolved chemical and metabolic stability issues.
In order to obtain comprehensive information regarding the metabolic fate, these peptides and derivatives were tested in vitro by incubation in buffer/denatured plasma, plasma and organ homogenates. A general screening procedure was used [3], where aliquots are withdrawn at pre-determined time points and analyzed by HPLC-UV/PDA-ESI/MS for determination of CAP degradation kinetics and identification of the degradation metabolites. Based on this information, QSPR (Quantitative Structure-Property Relationships) models can be built to predict the stability as a function of the peptide sequence (i.e. which peptide bonds are most unstable). Such a model can then be used to suggest directions for new CAPs with improved pharmaceutical drugability characteristics.

References:
[1]\unmatched{0009}Svenson J, Stensen W, Brandsdal BO, Haug BE, Monrad J, Svendsen JS. Antimicrobial peptides with stability toward tryptic degradation. Biochemistry 47 (2008) 3777-3788.
[2]\unmatched{0009}Strom MB, Haug BE, Skar ML, Stensen W, Stiberg T, Svendsen JS. The pharmacophore of short cationic antibacterial peptides. J Med Chem 46 (2003) 1567-1570.
[3]\unmatched{0009}Vergote V, Van Dorpe S, Peremans K, Burvenich C, De Spiegeleer B. In vitro metabolic stability of obestatin: Kinetics and identification of cleavage products. Peptides 29 (2008) 1740-1748.},
  author       = {Vergote, Valentijn and Svenson, Johan and Burvenich, Christian and Karstad, Rasmus and De Spiegeleer, Bart},
  booktitle    = {Faculty of Pharmaceutical Sciences 2009 Symposium, Abstracts},
  keyword      = {tripeptides,metabolic stability,Cationic antimicrobial peptides,mouse plasma},
  language     = {eng},
  location     = {Faculty of Pharmaceutical Sciences, Ghent University},
  title        = {Chemical and metabolic stability of lactoferricin-based cationic antimicrobial tripeptides},
  year         = {2009},
}

Chicago
Vergote, Valentijn, Johan Svenson, Christian Burvenich, Rasmus Karstad, and Bart De Spiegeleer. 2009. “Chemical and Metabolic Stability of Lactoferricin-based Cationic Antimicrobial Tripeptides.” In Faculty of Pharmaceutical Sciences 2009 Symposium, Abstracts.
APA
Vergote, V., Svenson, J., Burvenich, C., Karstad, R., & De Spiegeleer, B. (2009). Chemical and metabolic stability of lactoferricin-based cationic antimicrobial tripeptides. Faculty of Pharmaceutical Sciences 2009 Symposium, Abstracts. Presented at the Faculty of Pharmaceutical Sciences 2009 Symposium.
Vancouver
1.
Vergote V, Svenson J, Burvenich C, Karstad R, De Spiegeleer B. Chemical and metabolic stability of lactoferricin-based cationic antimicrobial tripeptides. Faculty of Pharmaceutical Sciences 2009 Symposium, Abstracts. 2009.
MLA
Vergote, Valentijn, Johan Svenson, Christian Burvenich, et al. “Chemical and Metabolic Stability of Lactoferricin-based Cationic Antimicrobial Tripeptides.” Faculty of Pharmaceutical Sciences 2009 Symposium, Abstracts. 2009. Print.