Peptide inhibitors of botulinum neurotoxin by mRNA display
| Autor: | David C.H. Yang, Seid Muhie, Kwabena P.A.B. Yiadom |
|---|---|
| Rok vydání: | 2005 |
| Předmět: |
medicine.medical_treatment
Molecular Sequence Data Biophysics Peptide Biology Biochemistry Neurotransmitter secretion Peptide Library medicine mRNA display Computer Simulation Amino Acid Sequence RNA Messenger Botulinum Toxins Type A Peptide library Molecular Biology Peptide sequence chemistry.chemical_classification Metalloproteinase Binding Sites Protease Cell Biology Molecular biology Fusion protein Models Chemical chemistry Peptides Protein Binding |
| Zdroj: | Biochemical and Biophysical Research Communications. 335:1247-1253 |
| ISSN: | 0006-291X |
| DOI: | 10.1016/j.bbrc.2005.07.196 |
| Popis: | Botulinum neurotoxins (BoNTs) are extremely toxic. The metalloproteases associated with the toxins cleave proteins essential for neurotransmitter secretion. Inhibitors of the metalloprotease are currently sought to control the toxicity of BoNTs. Toward that goal, we produced a synthetic cDNA for the expression and purification of the metalloprotease of BoNT/A in Escherichia coli as a biotin-ubiquitin fusion protein, and constructed a combinatorial peptide library to screen for BoNT/A light chain inhibitors using mRNA display. A protease assay was developed using immobilized intact SNAP-25 as the substrate. The new peptide inhibitors showed a 10-fold increase in affinity to BoNT/A light chain than the parent peptide. Interestingly, the sequences of the new peptide inhibitors showed abundant hydrophobic residues but few hydrophilic residues. The results suggest that mRNA display may provide a general approach in developing peptide inhibitors of BoNTs. |
| Databáze: | OpenAIRE |
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