- Author
- 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)
- Organization
- 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.
- Keywords
- screening, peptide drugs, organ-bath assays, receptor-ligand binding, quality
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Citation
Please use this url to cite or link to this publication: http://hdl.handle.net/1854/LU-667990
- MLA
- Verbeken, Mathieu, et al. Functional Quality of New Peptide Drugs: Receptor-Binding and Tissue-Interactions. 2009.
- APA
- Verbeken, M., Vergote, V., Burvenich, C., Van De Wiele, C., Ronai, A., Gyires, K., … De Spiegeleer, B. (2009). Functional quality of new peptide drugs: receptor-binding and tissue-interactions. Presented at the Symposium Farmaceutische Wetenschappen.
- Chicago author-date
- 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 .
- Chicago author-date (all authors)
- 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 .
- 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. In 2009.
- IEEE
- [1]M. Verbeken et al., “Functional quality of new peptide drugs: receptor-binding and tissue-interactions,” presented at the Symposium Farmaceutische Wetenschappen, 2009.
@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 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.}}, 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}}, keywords = {{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}}, }