查看更多>>摘要：Peptides are important natural bioactive substances obtained from various sources such as microbes, plants and animals. The present study addressed the optimization and physicochemical characterization of the antibacterial peptide Marine Fungal Antibacterial Peptide 9 (MFAP9) produced by the marine fungus Aspergillus fumigatus BTMF9 and the in vitro evaluation of its antiproliferative, antioxidant and anti-inflammatory potential. Antiproliferative activity was evaluated in A549 lung carcinoma and normal L929 fibroblast cell lines using the MTT assay. Antioxidant activity was evaluated by DPPH assay and anti-inflammatory studies were performed by Cox2 inhibition assay on THP1 cell lines. The results showed that MFAP9 was cytotoxic against A549 cells with an IC50 value of 29 mu g/mL and exhibited apoptotic properties after treatment with a concentration of 50 mu g/mL. In addition, MFAP9 showed higher DPPH radical scavenging activity than standard antioxidants at the same concentration and significant anti-inflammatory activity. The rate of MFAP9 production was optimized by a time course experiment. Characterization revealed that the maximum active temperature of MFAP9 is 50 degrees C, that it is stable at basic pH, and that 1 mM concentrations of Ni2+, Cd2+, and Mg2+ promote peptide activity. It is hoped that MFAP9 could become a promising new therapeutic agent for various clinical applications by using advances in proteomics, bioinformatics and modification strategies.
查看更多>>摘要：The present study was designed to investigate the anti-inflammatory activity of atrial natriuretic peptide (ANP) using lambda-Carrageenan (lambda-CAN)-induced acute inflammation in the mice model. A single subplantar injection of lambda-CAN (1% in 0.9% saline) triggers acute paw edema. ANP (2 mu g/kg body weight/day/i.p) was given 30 min prior or after administration of lambda-CAN. The standard drug Aspirin (ASP) treated group was used as a positive control. A marked increase in paw thickness (32.56% p < 0.001) and thermal pain latency (0.82 +/- 0.03 vs 3.6 +/- 0.12; P < 0.001) were noticed in lambda-CAN-induced mice as compared with control. The level of pro-inflammatory marker genes such as Nuclear factor-kappa B and Cyclooxygenase-2 were significantly increased (p < 0.001 respectively) in lambda-CAN-induced mice as compared with control. A similar trend was noticed in pro-inflammatory cytokines such as Interleukin-6, Interleukin-1 beta, Tumour necrosis factor-alpha and Prostaglandin E2 (p < 0.001 respectively). On the contrary, ANP exhibits a marked reduction in paw edema thickness (pre-8.76% and post-9.12%, p < 0.001) and thermal pain latency in both pre-0.82 +/- 0.03 vs 1.2 +/- 0.06 and post-0.82 +/- 0.03 vs 1.6 +/- 0.02 (P < 0.001) were noticed in ANP pre-and post-treated group. Further myeloperoxidase activity, pro-inflammatory marker genes and pro-inflammatory cytokines were also reverted (p < 0.01 respectively) to near-normal levels. The present study results suggest that pre-and post-treatment of ANP positively neutralizes the lambda-CAN induced acute edematic and inflammatory responses. The anti-edematic and anti-inflammatory action of ANP was found to be much more effective than that of the non-steroidal drug aspirin (ASP).
查看更多>>摘要：Breast cancer is the most frequent cancer in women worldwide. Human epidermal growth factor receptor 2 (HER2) is a receptor which is overexpressed in breast cancer cells. Targeting this receptor could be a key factor for treatment of breast cancer patients. Herceptin is an antibody which can bind to HER2 receptor, in addition Herceptin derived single chain fragment V (scFv) can be used in designing immunotoxin for targeting HER2 positive cancer cells. DFF40 is a nuclease activated by caspase-3 and responsible for genomic DNA fragmentation during apoptosis. In this study, we used bioinformatics tools to design an immunotoxin containing HER2 specific scFv and DFF40 toxin. An immunotoxin construct was designed by linking scFv and DFF40 amino acids sequence via a peptide linker. The secondary structure, physicochemical features, solubility, and allergenicity of construct were predicted. The tertiary structure was built, refined, and evaluated. Protein-protein docking, and molecular dynamics studies were carried out for evaluation of immunotoxin-receptor binding, and the stability of the immunotoxin, respectively. The results indicated that the designed construct could be a stable protein with appropriate solubility, which is not an allergen and has a suitable structure which can bind to HER2 appropriately. Finally, this construct could be a promising candidate for producing an HER2 targeting immunotoxin. However, different in vitro and in vivo immunological assays should be performed to confirm the efficacy of the designed construct.
Shoari, AlirezaKhalili, SaeedRasaee, Mohammad JavadLowik, Dennis W. P. M....
11页
查看更多>>摘要：Matrix metalloproteinases (MMPs) play critical roles in the invasiveness of cancerous cells and metastasis of solid tumors. MMP-9 is a member of this protease family, which is extremely overexpressed in metastatic cells. Here, we described a cyclic peptide which inhibits the MMP-9 activity with high potency. This inhibitor selectively binds to the MMP-9 fibronectin domain and interferes with the interaction of gelatinous substrates with MMP-9, thereby suppressing its gelatinolytic activity. Previously, we isolated and developed a linear peptide, named as RSH-12, from a phage display library which displayed promising results in the inhibition of MMP-9. Next, we decided to improve its biostability via cyclization chemistry and show that RSH-12 has a considerably enhanced stability in human serum. Moreover, the cyclic peptide is still associated with a high potency to inhibit the invasion activity of a human fibrosarcoma cell line. These results demonstrate that the designed cyclic peptide might be considered as a promising therapeutic moiety to target the MMP-9 for the treatment of cancer.
查看更多>>摘要：Biologically active plant peptides, consisting of secondary metabolites, are compounds (amino acids) utilized by plants in their defense arsenal. Enzymatic processes and metabolic pathways secrete these plant peptides. They are also known for their medicinal value and have been incorporated in therapeutics of major human diseases. Nevertheless, its limitations (low bioavailability, high cytotoxicity, poor absorption, low abundance, improper metabolism, etc.) have demanded a need to explore further and discover other new plant compounds that overcome these limitations. Keeping this in mind, therapeutic plant proteins can be excellent remedial substitutes for bodily affliction. A multitude of these peptides demonstrates anti-carcinogenic, anti-microbial, anti-HIV, and neuro-regulating properties. This article's main aim is to list out and report the status of various therapeutic plant peptides and their prospective status as peptide-based drugs for multiple diseases (infectious and non-infectious). The feasibility of these compounds in the imminent future has also been discussed.
Melendez-Zempoalteca, AlejandraJuarez-Gonzalez, Victor RivelinoRudino-Pinera, EnriquePastor, Nina...
13页
查看更多>>摘要：Scorpionism in Mexico is a public health problem caused by stings from the Centruroides scorpion family. The Ct1a and Ct17 toxins from the venom of the Centruroides tecomanus scorpion are the most abundant and toxic for mammals. This study describes the heterologous expression of recombinant proteins from genes encoding these toxins merged with thioredoxin in the vector pET-22b + and expressed in Escherichia coli BL21 (DE3). The yield of Ct1a and Ct17 recombinant toxins was 1.25 mg and 1.737 mg per liter of culture, respectively. These were purified by metal ion affinity chromatography and RP-HPLC and were used for immunization in rabbits, obtaining polyclonal antibodies that confer a positive immune response against the complete venom of Centruroides tecomanus. The serum was tested in vitro and in vivo, obtaining neutralization and protection against the venom. Both toxins were produced recombinantly and fused to the thioredoxin protein; remarkably, the recombinant toxins were excellent immunogens. 300 mu l of each immunized rabbit serum was tested in mice, resulting in 50% of the mice protected with each serum, but when the sera were pooled, the protection increased to 83%. This communication reveals the possibility of producing a specific and regional antivenom with polyclonal antibodies that neutralize the complete venom of Centruroides tecomanus. The sequence similarity of Ct1a and Ct17 to Cn2, a toxin that recognizes sodium channels, allowed in silico modeling analysis and a proposal for the different toxicities of Ct1a and Ct17.
查看更多>>摘要：Tuberculosis (TB) is one of the leading cause of death worldwide, and the world is fighting with this global health emergency from the past 25 year. The current clinical interventions for the management of TB face a number of inherent challenges which includes low patient compliance due to the long therapy regimen, and emerging antimicrobial resistance. Therefore, there is an unmet need of new anti-TB therapeutic agent with enhanced safety profile, which can reduce the duration of therapy, enhanced bioavailability and efficacy against drug resistant forms of TB. Bacteriocins or anti microbial peptides (AMPs) occurring in microbes, human beings and other life forms have been investigated as host defense peptides. Structurally AMPs are short and ionized and play crucial role in innate immunity of host. Some AMPs can kill microbial infections directly while others function indirectly by altering the host defense mechanisms. Amidst rising issue of antibiotic resistance, AMPs are being tested in clinical research as potential antibiotics and novel therapeutics to fight against infections and non-infectious diseases. Studies have also highlighted the ability of AMPs to act against the bacteria spreading tuberculosis. The present review provides information on antimicrobial peptides, highlights their biological role, classification and mode of action in treatment and prevention of tuberculosis. It further mentions the prospects and challenges of developing peptides for their therapeutic applications against mycobacterium tuberculosis.
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