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Functional quality of new peptide drugs: receptor-binding and tissue-interactions

Mathieu Verbeken UGent, Valentijn Vergote UGent, Christian Burvenich UGent, Christophe Van De Wiele UGent, Andras Ronai, Klara Gyires, Walter Luyten and Bart De Spiegeleer UGent (2009)
abstract
The biomedical effects of peptide pharmaceuticals, not only lead drug structures but their derived fragments, label-modified analogues, metabolites, related synthesis and degradation impurities for qualification evaluation as well, are studied using receptor-ligand-binding (RLB) and tissue-bath (TB) experiments. The importance of such a biomedical, functional quality, screening approach is substantiated by the wide variety of physiological effects already seen with known peptides. However, errors of the type I (false positives or α) and type II (false negatives or β) need to be minimized and controlled. On the other hand, literature data indicate a variety of operational conditions, often without much justification. In RLB studies, multivariate experimental designs (DOE) are evaluated as a strategy to minimize false negatives. The usefulness of this DOE-approach was demonstrated by a study of 125I-VIP interaction with its receptors in rat lung tissue [1]. The RLB incubation conditions as well as the filtration step were investigated. Not only optimal conditions could be assigned, but mechanistic explanations and new findings result from this DOE, e.g. adsorption effects are decreased by the presence of the protease-inhibitor bacitracin. The isolated organ assay using tissue baths (TB) allows the study of complex physiological responses with unknown molecular target receptors, often observed with peptides. The effect on smooth muscle contraction of peptide-mixtures is tested covering 5 different tissues from different species: vas deferens (mouse), aortic rings and fundus strips (rat), trachea and ileum longitudinal muscle strips (guinea pig). Different experimental conditions are used to extract maximal useful information.
Please use this url to cite or link to this publication:
author
organization
year
type
conference
publication status
published
subject
keyword
screening, peptide drugs, organ-bath assays, receptor-ligand binding, quality
conference name
Symposium Farmaceutische Wetenschappen
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
667990
handle
http://hdl.handle.net/1854/LU-667990
date created
2009-05-27 10:35:22
date last changed
2009-05-28 10:44:06
@inproceedings{667990,
  abstract     = {The biomedical effects of peptide pharmaceuticals, not only lead drug structures but their derived fragments, label-modified analogues, metabolites, related synthesis and degradation impurities for qualification evaluation as well, are studied using receptor-ligand-binding (RLB) and tissue-bath (TB) experiments. The importance of such a biomedical, functional quality, screening approach is substantiated by the wide variety of physiological effects already seen with known peptides. However, errors of the type I (false positives or \ensuremath{\alpha}) and type II (false negatives or \ensuremath{\beta}) need to be minimized and controlled. On the other hand, literature data indicate a variety of operational conditions, often without much justification.

\unmatched{0009}In RLB studies, multivariate experimental designs (DOE) are evaluated as a strategy to minimize false negatives. The usefulness of this DOE-approach was demonstrated by a study of 125I-VIP interaction with its receptors in rat lung tissue [1]. The RLB incubation conditions as well as the filtration step were investigated. Not only optimal conditions could be assigned, but mechanistic explanations and new findings result from this DOE, e.g. adsorption effects are decreased by the presence of the protease-inhibitor bacitracin.

\unmatched{0009}The isolated organ assay using tissue baths (TB) allows the study of complex physiological responses with unknown molecular target receptors, often observed with peptides. The effect on smooth muscle contraction of peptide-mixtures is tested covering 5 different tissues from different species: vas deferens (mouse), aortic rings and fundus strips (rat), trachea and ileum longitudinal muscle strips (guinea pig). Different experimental conditions are used to extract maximal useful information.},
  author       = {Verbeken, Mathieu and Vergote, Valentijn and Burvenich, Christian and Van De Wiele, Christophe and Ronai, Andras and Gyires, Klara and Luyten, Walter and De Spiegeleer, Bart},
  keyword      = {screening,peptide drugs,organ-bath assays,receptor-ligand binding,quality},
  language     = {eng},
  title        = {Functional quality of new peptide drugs:  receptor-binding and tissue-interactions},
  year         = {2009},
}

Chicago
Verbeken, Mathieu, Valentijn Vergote, Christian Burvenich, Christophe Van De Wiele, Andras Ronai, Klara Gyires, Walter Luyten, and Bart De Spiegeleer. 2009. “Functional Quality of New Peptide Drugs:  Receptor-binding and Tissue-interactions.” In .
APA
Verbeken, M., Vergote, V., Burvenich, C., Van De Wiele, C., Ronai, A., Gyires, K., Luyten, W., et al. (2009). Functional quality of new peptide drugs:  receptor-binding and tissue-interactions. Presented at the Symposium Farmaceutische Wetenschappen.
Vancouver
1.
Verbeken M, Vergote V, Burvenich C, Van De Wiele C, Ronai A, Gyires K, et al. Functional quality of new peptide drugs:  receptor-binding and tissue-interactions. 2009.
MLA
Verbeken, Mathieu, Valentijn Vergote, Christian Burvenich, et al. “Functional Quality of New Peptide Drugs:  Receptor-binding and Tissue-interactions.” 2009. Print.