Identification of novel peptide inhibitors for human trypsins
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Ping Wu
Abstract
Human trypsin isoenzymes share extensive sequence similarity, but certain differences in their activity and susceptibility to inhibitors have been observed. Using phage display technology, we identified seven different peptides that bind to and inhibit the activity of trypsin-3, a minor trypsin isoform expressed in pancreas and brain. All of the peptides contain at least two of the amino acids tryptophan, alanine and arginine, whereas proline was found closer to the N-terminus in all but one peptide. All peptides contain two or more cysteines, suggesting a cyclic structure. However, we were able to make synthetic linear variants of these peptides without losing bioactivity. Alanine replacement experiments for one of the peptides suggest that the IPXXWFR motif is important for activity. By molecular modeling the same amino acids were found to interact with trypsin-3. The peptides also inhibit trypsin-1, but only weakly, if at all, trypsin-2 and -C. As trypsin is a highly active enzyme which can activate protease-activated receptors and enzymes that participate in proteolytic cascades involved in tumor invasion and metastasis, these peptides might be useful lead molecules for the development of drugs for diseases associated with increased trypsin activity.
©2010 by Walter de Gruyter Berlin New York
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Artikel in diesem Heft
- EDITORIAL
- Highlight: Signal Transduction and Disease
- HIGHLIGHT: SIGNAL TRANSDUCTION AND DISEASE
- Phosphorylase and the origin of reversible protein phosphorylation
- β-Catenin as a multilayer modulator of zonal cytochrome P450 expression in mouse liver
- Glycome profiling using modern glycomics technology: technical aspects and applications
- Ubiquitin ligase complexes: from substrate selectivity to conjugational specificity
- MAP3K1 functionally interacts with Axin1 in the canonical Wnt signalling pathway
- Signal transduction by the atopy-associated human thymic stromal lymphopoietin (TSLP) receptor depends on Janus kinase function
- GENES AND NUCLEIC ACIDS
- 6S RNA-dependent inhibition of RNA polymerase is released by RNA-dependent synthesis of small de novo products
- PROTEIN STRUCTURE AND FUNCTION
- Analysis of the DNA-binding activity of p53 mutants using functional protein microarrays and its relationship to transcriptional activation
- Peptides from the Mycobacterium tuberculosis Rv1980c protein involved in human cell infection: insights into new synthetic subunit vaccine candidates
- The epimerase activity of anthocyanidin reductase from Vitis vinifera and its regiospecific hydride transfers
- Antibacterial activity of radical scavengers against class Ib ribonucleotide reductase from Bacillus anthracis
- CELL BIOLOGY AND SIGNALING
- Signal transduction in CHO cells stably transfected with domain-selective forms of murine ACE
- The impact of methylmercury on 1,25-dihydroxyvitamin D3-induced transcriptomic responses in dolphin skin cells
- PROTEOLYSIS
- An examination of the proteolytic activity for bovine pregnancy-associated glycoproteins 2 and 12
- Analysis of an autoproteolytic activity of rice yellow mottle virus silencing suppressor P1
- Identification of novel peptide inhibitors for human trypsins
