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Antimicrobial effects of vertebrate TFPI-2 C-terminal peptides2016-11-30
Article from our customer: Kasetty et al. BMC Microbiology (2016) 16:129
Background: In previous studies we reported a novel role of human tissue factor pathway inhibitor-2 (TFPI-2) in innate immunity by serving as a precursor for host defense peptides. Here we further studied the therapeutic potential of one selected TFPI-2 derived peptide (mouse) in a murine sepsis model.
Results: A number of selected C-terminal TFPI-2 derived peptides from different species were synthesized and it was found that all of them exert antimicrobial activity against E.coli and P. aeruginosa. The peptide-mediated killing of E. coli was enhanced in human plasma, suggesting an involvement of the classical pathway of the complement.
Conclusion: Our results suggest that the evolutionary conserved C-terminal part of TFPI-2 is an interesting agent for the development of novel antimicrobial therapies.
Fig.6 Treatment of LPS-induced septic shock mice with a mouse TFPI-2 derived peptide. Septic shock in Balb/c mice was induced by i.p. injection of 10 mg/kg E. coli LPS. Thirty minutes after LPS injection, VKG24 (0.5 mg/mouse or ~25 mg/kg body weight) or PBS was administratedi.p. (a)Mouse TFPI-2 derived peptide significantly increased survival of mice. Survival of mice was monitored for 7 days (only the first 96 h is shown in the figure). Statistical comparisons of survival curves were performed using the Mantel-Cox’s test. ***P ≤ 0.0003. (b)Weight was determined daily. (c)Clotting times of aPTT and PT was measured in citrate plasma 24 h after LPS injection (n = 8). (d)The indicated cytokines were analyzed in plasma 24 h after LPS injection (n = 8). Statistical analysis for C-D, one-way ANOVA with Tukey’s multiple comparisons post-test was used. **P ≤ 0.003, ****P ≤ 0.0001
All of the peptides used in this article were synthesized by Ontores (Shanghai, China). The purity (>98 %) of these peptides was confirmed by mass spectral analysis (MALDI-TOF Voyager).
Peptide modified liposomes with active recognizing of integrin αvβ3 for the treatment of melanoma2016-11-16
Article from our customer: Kairong Shi, Journal of Controlled Release,2015.
Background: The use of pH-responsive cell-penetrating peptides (CPPs) is an attractive strategy for drug delivery in vivo, however, they still could not actively target to the desired sites. Here, we designed a pH-responsive CPP (TR) with the ability of active targeting to integrin αvβ3.
Results: TR-Lip could not only actively target to αvβ3-overexpressing cells compared to TH-Lip, but also significantly increased cellular uptake compared to RGD-Lip. At the concentration of 20 μg/mL paclitaxel (PTX), the killing activity of PTX-loaded TR-Lip (PTX-TR-Lip) against B16F10 cells was 1.80-, 1.45-, 1.30-, 1.15-time higher than that of PTX-loaded PEG-, RGD-, TH-modified liposomes and free PTX at pH 6.5, respectively. In vivo imaging displayed the maximum accumulation of DiD-labeled TR-Lip at tumor sites compared to the other groups. Tumor inhibition rate of B16F10 tumor-bearing mice treated with PTX-TR-Lip was 85.04%, relative to that of PBS. In B16F10 tumor-bearing mice, PTX-TR-Lip showed significantly higher survival rate compared with the other groups.
Conclusion: All the results in vitro and in vivo suggested that TR-Lip would be a potential delivery system for PTX to treat integrin αvβ3-overexpressing tumor-bearing mice.
Fig. 1. Schematic design of TR-Lip for integrin αvβ3-overexpressing tumor-targeted drug delivery. Tumor pH-induced TR-Lip for selective targeting to integrin αvβ3-overexpressing cells, improved cellular uptake, and enhanced tumor penetration.
In this article, TH peptide with a terminal cysteine (AGYLLGHINLHHLAHL(Aib)HHILCys), TR peptide with a terminal cysteine [c(RGDfK)-AGYLLGHINLHH LAHL(Aib)HHIL-Cys,lysine connected with alanine by covalent bonds]
were synthesized according to the standard solid phase peptide synthesis by ZheJiang Ontores Biotechnologies Co. Ltd. (Hangzhou, China).
As a leading Biotech company over world, Ontores committed to provide professionally high quality and comprehensive proteomic and genomic industry solution to our global customers. Ontores offers innovative solutions for antibodies, building blocks, oligonucleotides and peptides and carries a broad spectrum of bio-reagents that will meet everyone’s need in their multi-disciplinary research. Ontores also provides cutting edge custom services including antibody production, contract research services and peptide synthesis.