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A bradykinin potentiating peptide (BPP), Thr-Pro-Pro-Ala-Gly-Pro-Asp-Val-Gly-Pro-Arg-OH, was isolated from the venoms of Crotalus viridis viridis (here named Cvv peptide). Compared with other BPP, Cvv peptide has special Thr at N-terminal and Arg at C-terminal. In order to clarify whether these two special amino acids lead to special bioactivities relative to other BPPs, we made bioassays on isolated guinea pig ileum (GPI) and rat stomach fundus. Cvv peptide can observably inhibit bradykinin's contractivity on GPI, but potentiate the bradykinin-induced contractivity on rat stomach fundus. The discrepant bioactivity of Cvv peptide may occur via binding different receptors, B2 receptor on GPI and anaphylatoxin C3a receptor on rat stomach fundus, respectively.

To investigate the effect and mechanism of nociceptin/orphanin FQ (OFQ) reversing multi-drug resistance of K562/ADM cells in vitro.MTT assay, Wright staining, flow cytometry, transmission electron microscope and gel electrophoresis were used to evaluate the effect and mechanism of OFQ in reversing multi-drug resistance of K562/ADM cells.OFQ could time-dependently reverse the ADM resistance of K562/ADM cell. After treatment with OFQ (1 x 10(-7) mol x L(-1)), K562/ADM cells were cultured for 24, 48 and 72 h. The reversal index (RI) was 1.33, 1.42 and 1.53, respectively. Furthermore, OFQ significantly increased the intracellular accumulation of ADM in K562/ADM cells and percentage apoptosis in K562/ADM cells. OFQ down-regulated the level of P-gp time-dependently, while the level of Fas and FasL were up-regulated. There were evidently significant differences compared with the control (P0.01). After treating K562/ADM cells with OFQ (1 x 10(-7) mol x L(-1)) and ADM (20 microg x ml(-1)) for 48 hours, the cells showed apoptotic nuclear fragmentation, which was characterized by the appearance of a DNA ladder pattern in genomic DNA gel electrophoresis.OFQ can reverse the ADM resistance of K562/ADM cells. The mechanism involves OFQ up-regulating the expression of Fas/FasL, down-regulating the level of P-gp, and decreasing the intracellular level of calcium in K562/ADM cells.

The prion protein is usually pictured as globular structured C-terminal domain that is linked to an extended flexible N-terminal tail. However, in its physiological form, it is a glycoprotein tethered to the cell surface via a C-terminal GPI anchor. The low solubility of PrP even without GPI anchor and its strong tendency for aggregation has forced most structural investigations to be performed at low pH and mostly with N-terminally truncated variants. In the present study, we have used a synthetic peptide related to the PrP tetra-octarepeat region, i.e., the sequence (Pro-His-Gly-Gly-Gly-Trp-Gly-Gln)4, for NMR structural analysis of its preferred conformation in DPC micelles as membrane mimic. Well-defined and identical loops are observed between the four octarepeats that are linked by flexible Gly-Gly-Gly sequences. Interaction with the micelles is mainly through the tryptophan residues that appear to act as anchors. Copper binding to the peptide in the presence of DPC micelles revealed marked conformational rearrangements although binding to the micelles is preserved. Interestingly, titration experiments point to cooperative effects for the four binding sites. A destabilization of the DPC micelles by the peptide parallels the destabilizing effect of the prion protein on membranes so that the octarepeat region appears to be very membrane-active. How the physico–chemical properties reported here are linked to the function and significance of the prion protein remains a puzzle as long as the functional mechanism of the prion protein is not precisely elucidated. Nevertheless, our results emphasize the strong influence of the (membrane) environment on the PrP properties. © 2007 Wiley Periodicals, Inc. Biopolymers (Pept Sci) 88: 840–847, 2007. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com