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Conformational and biological properties of Bauhinia bauhinioides kallikrein inhibitor fragments with bradykinin-like activities.
- Source :
-
Journal of peptide science : an official publication of the European Peptide Society [J Pept Sci] 2015 Jun; Vol. 21 (6), pp. 495-500. Date of Electronic Publication: 2015 Apr 21. - Publication Year :
- 2015
-
Abstract
- Proteinase inhibitors extracted form medicinal plants are an interesting source of new drugs. Modifications in the structure of some of this kind of macromolecules could also lead to compounds of interesting biological properties. In this work, we synthesized and tested one fragment containing the reactive site of the Bauhinia bauhinioides kallikrein inhibitor (BbKI), denoted BbKI51-62 , and a related analog (P2 ) in which a proline residue was inserted in order to mimic the N-terminal region of the bradykinin molecule. The related retro-inverso counterparts Ri-BbKI51-62 and Ri-P2 were also included. The ability of these peptides to induce contraction of stomach fundus isolated from mouse was evaluated as well as their capability to induce calcium release from a cell culture of smooth muscle from guinea pig ileum. The conformational properties of the peptides were evaluated by circular dichroism and their resistance to enzymatic degradation by exposure to human blood plasma. Our results show that neither the parent BbKI51-62 nor its Ri-BbKI51-62 analog exhibit bradykinin-like activity, although the retro-inverso isomer was resistant to blood plasma degradation. On the other hand, the peptides P2 and Ri-P2 presented contractile activities on gastric smooth muscle from stomach fundus possibly by acting via B-2 receptor. Both compounds also induce calcium release from guinea pig ileum muscle cells in a manner similar to bradykinin. Moreover, both compounds also inhibited porcine pancreatic kallikrein. However, conformational analysis did not reveal any direct correlation between structure and biological effects.<br /> (Copyright © 2015 European Peptide Society and John Wiley & Sons, Ltd.)
- Subjects :
- Animals
Calcium metabolism
Cells, Cultured
Enzymes blood
Guinea Pigs
Humans
Ileum cytology
Ileum drug effects
Mice
Protein Structure, Secondary
Proteolysis
Receptor, Bradykinin B2 metabolism
Stomach drug effects
Swine
Bradykinin analogs & derivatives
Muscle Contraction drug effects
Peptides chemistry
Peptides pharmacology
Plant Proteins chemistry
Plant Proteins pharmacology
Plants, Medicinal chemistry
Subjects
Details
- Language :
- English
- ISSN :
- 1099-1387
- Volume :
- 21
- Issue :
- 6
- Database :
- MEDLINE
- Journal :
- Journal of peptide science : an official publication of the European Peptide Society
- Publication Type :
- Academic Journal
- Accession number :
- 25902925
- Full Text :
- https://doi.org/10.1002/psc.2766