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Platypus
Technologies - Oris™ Cell Migration Assembly Kit - FLEX
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Product
Number |
Description |
Pkg
Size |
| PPCMAUFL4 |
Oris™ Cell Migration Assembly Kit
- Flex |
Kit |
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Active
Motif - UnMethylCollector™ KitThe UnMethylCollector™ Kit* is the first commercially available kit for the specific isolation of hypomethylated CpG islands. The kit utilizes the CXXC domain from mouse Mbd1, which is able to specifically bind unmethylated CpG dinucleotides from as little as 1600 cells (~10 ng DNA).
Click here to view the UnMethylCollector™ manual.
Product
Number |
Description |
Pkg
Size |
| AM55004 |
UnMethylCollector™ |
30 rxns |
* Patent Pending
MethylCollector™ Ultra* is an improved technology for the enrichment of CpG-methylated DNA. The kit combines the His-tagged MBD2b protein with its binding partner MBD3L1 to generate higher affinity and better specificity for CpG-methylated DNA than other methyl-binding protein or antibody immunoprecipitation methods.
Click here to view the MethylCollector™ Ultra manual
Product
Number |
Description |
Pkg
Size |
| AM55005 |
MethylCollector™ Ultra |
30 rxns |
* Technology is covered under U.S. Patent No. 7.425.415

Labnet's Revolver accepts a variety of tube sizes and mixes them horizontally, vertically, or any position in between. Changing the mixing angle is easy! simply turn the rotisserie. No tools are required.
Product
Number |
Description |
Pkg
Size |
| LNH5600 |
Revolver Tube Mixer (with rotisserie for 36 x 1.5mL tubes), 120V |
Each |
| LNH560015 | Rotisserie for 10 x 15 mL tubes & 12 x 5/7 mL tubes | Each |
| LNH560050 | Rotisserie for 6 x 50 mL tubes | Each |
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Simport
- EconoTube™
For pricing information, contact our Customer Service Team at 1-888-593-5969 or sales@biolynx.ca.
Product
Number |
Description |
Pkg
Size |
| SPT330N5 |
EconoTube™, 1.5 mL, PP |
5000 |
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Active
Motif - Transcription Biology BrochureThis new brochure features transcription
factor and nuclear receptor ELISAs, chromatin assays and IP kits,
luciferase assays, supershift & gelshift assays.
Click here for
the on-line PDF.
Contact our Technical Support Team
to request printed copies.
Associates
of Cape Cod Inc. - LAL Update, April 2009In this issue: Controls for Photometric
Tests: Implications for Low Capacity Test Systems
by Robert Porzio and Michael Dawson, Ph.D., RAC.
Click here for the
on-line PDF.
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Meridian
Life Science, Inc. (MLS) is offering a limited number of Free Pilot
Runs of ascites production of monoclonal antibodies. This time sensitive
promotion is for qualified companies who have needs for bulk production.
Please contact our Technical Support Team to inquire.
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From
April 1st to June 30th, 2009
Accumulate purchases of 5 Abgent antibodies* and receive a $50 gift
card for Laura Secord Chocolates.
Abgent antibodies are widely used in the fields of :
|
|
Click
here for details.
* Offer is not applicable to Abgent Antibody Sampler Kits.
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Measure
the relative abundance of 46 human cancer-related proteins
with the single-capture antibody array.
Use
the arrays with the SIMplex™ 16 Multi-Array System for:
Click here
for promotion details.
Offer valid from April 1st to May 29th, 2009
ChIP-IT™
Express HT allows you to perform chromatin IP in a fast, reproducible
high-throughput format. It combines the efficiency of the groundbreaking
magnetic bead-based ChIP-IT™ Express Kit with a 96-well plate
format, enabling the rapid and efficient processing of a large number
of ChIP reactions.
This offer is available while quantities
last
Click
here for promotion details
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Hsp90 is one of a number of classes of heat shock proteins (Hsps), which are generally synthesized in response to cellular stress as well as being constitutively expressed in some cases. These types of stress are numerous, but include heat shock, metal toxicity, nutrient deprivation, oxidative stress as well as numerous disease states of which cancer has received the most attention. Hsps function is several ways, but have the ability to form complexes with client proteins and act as molecular chaperones. These complexes are themselves directly involved in protein folding in the cytosol, endoplasmic reticulum (ER) and mitochondria, the intracellular transport of proteins, protein repair and degradation (of environmentally damaged proteins), regulatory protein control, and the re-folding of misfolded proteins. The Hsps have been generally classified into several classes depending on their molecular weights, see Table 1.
Table 1*Name |
Localization |
Function |
| Hsp104 |
Cytoplasm |
Releases proteins from aggregates |
| Hsp90a and ß | Cytoplasm | Prevents protein aggregation, enables protein stabilization and trafficking, facilitates activation of numerous regulated proteins |
| Grp94 | Endoplasmic reticulum | Quality control of protein processing in the endoplasmic reticulum |
| TRAP/Hsp25 | Mitochondria | Unclear |
| Hsp70/Hsc70 | Cytoplasm | Prevents protein aggregation, aids protein folding |
| Grp78/Bip | Endoplasmic reticulum | Protein import and folding in the endoplasmic reticulum |
| Hsp60/Chaperonins | Cytoplasm and mitochondria | Prevents protein aggregation, aids protein folding |
| Hsp47 | Endoplasmic reticulum | Facilitates the folding and assembly of procollagen molecules, retaining unfolded molecules within the ER, and assisting the transport of correctly folded molecules from the ER to the Golgi apparatus. |
| Hsp40/HDJ2 | Cytoplasm | Helps protein folding as a co-chaperone of hsp70 |
| Hsp32 (HO-1; small Hsps) | Endoplasmic reticulum, plasma membrane and mitochondria | Catalyzes first step of heme degradation to bilirubin, which has antioxidant properties. |
| Hsp27/25 (small Hsps) | Endoplasmic reticulum | Prevents protein aggregation, may have role in cell growth and differentiation |
| Alpha B crystalline (small Hsps) | Cytoplasm | Major eye lens protein. Alpha B-crystallin inhibits TRAIL induced apoptosis in cancer. It confers a cyto-protective effect by suppressing aggregation of denatured proteins. It is constitutively expressed, often at high levels, in human cancers, including gliomas, breast, prostate and renal cell carcinomas. |
*Adapted from Annals in Oncology, 14: 1169-1176, 2003
Hsp90 is one of the most prevalent chaperone proteins present in the cell – it can represent 1-2% of unstressed cell’s protein and as much as 6% in the stressed cell. It has the ability to provide multi-component complexes which have been shown to include p60/Hop, p50Cdc37, Hsp40/HDJ2, p23, Hsp70 and one of a number of immunophilins (such as FKBP51 and FKBP52). Hsp90 itself is present in two forms, Hsp90a and ß. Both proteins are highly related and appear to have identical activities, however, the former is inducible whereas the latter is constitutively expressed. Hsp90 is also a phospho-protein – and has two or three bound phosphate molecules per monomer and exists as a homodimer. One of the clear distinctions that have made it a potential drug target are the fact that a significant amount of its client proteins are protein kinases. These client proteins include ErbB2/Her-2, EGFR, Hif1a, c-Met, Akt/PKB, Raf-1, Cdk-1 and 4, Aurora B, Ask1, CHK1, CKII as well as mutant p53. Furthermore, due to the nature of the interactive and complex network that is associated with regulating cell proliferation and cell death, the approach of identifying one specific (drug) target and blocking or activating it can result in the cell simply altering it’s regulation in order to maintain the phenotype. The wide amount of Hsp90 client proteins and the fact that many of them are directly involved in regulatory (signaling and phosphorylation) processes have allowed researchers to take a wider target approach to shutting down activities associated with cancers and stepping around the redundancies of the multiple signaling routes.
Hsp90 has been widely studied in relation to steroid receptors, despite the first recognized substrate being discovered to be pp60v-sr. These studies have elucidated that the receptors must be bound to Hsp90 to have a high binding affinity for steroids. The Hsp90 assembly also showed the importance of the presence of p23 and Hop, working together with Hsp70 and Hsp90 as a multi-protein machine. Together with Hsp40, these five proteins work together to produce receptor-Hsp90 heterocomplexes with steroid-binding activity. Mechanistic studies have indicated the steps involved in the assembly, starting with two sequential ATP-dependent events involving first hsp70 and then hsp90. Interestingly, since the chaperone machinery reveals a hydrophobic steroid-binding cleft to access the ligand, the action of Hsp90 as part of the multi-protein machinery is quite different from that of hsp90 acting alone in vitro to promote reactivation of partially denatured enzymes. The three hsp90-binding tetratricopeptide repeat (TPR) domain immunophilins - FKBP52, FKBP51, and CyP-40- were discovered as components of steroid receptor-hsp90 heterocomplexes.
Steroid-mediated glucocorticoid receptor translocation from the cytoplasm to the nucleus has led to the discovery that the TPR domain immunophilins link Hsp90 to a dynein motor protein. The mechanistic conclusions derived from elucidation of how the Hsp90 machinery works with the steroid receptor appears to provide a broad set of principles of how Hsp90 works, which would be in contrast to other cell stress protein chaperone studies. The latter would indicate that in order to be a substrate for Hsp90 or Hsp70 the presence (some degree) of unfolded protein would be required – however there have been no indications for the steroid receptor studies that receptors are in any way denatured. When Hsp90 and Hsp70 act together a highly focal site of attack is located on the glucocorticoid receptor that is situated on the surface of the ligand-binding domain at the opening of the hydrophobic steroid-binding cleft. However, whether or not Hsp90 has the general ability to recognize cleft openings on other signaling proteins is unclear, but due to the fact that they are present on almost all protein as a topological feature it is possible that the Hsp90 and Hsp70 complex recognizes these native rather than denatured conformations.
Currently, high interest has been manifest in benzoquinone ansamycin antibiotics (BA), which include herbimycin, geldanamycin and 17-allylamino-17-demethoxygeldanamycin (17-AAG), a drug class capable of affecting multiple targets in tumor cell pathways by binding to Hsp90. 17-AAG has also been modified to make 17- dimethylaminoethylamino - 7 - demethoxygeldanamycin (17-DMAG) to improve drug half-life and water solubility. These drugs bind Hsp90 at a conserved 25kD N-terminal domain which is responsible for ATP binding, hence disrupting the Hsp90 chaperone complex. Other inhibitors include radicicol, the chemotherapeutic agent cisplatin, taxol, as well as the antibactericide novobiocin. Cisplatin binds to a novel nucleotide-binding site of Hsp90 at its C-terminus, while novobiocin binds to several domains of Hsp90. This leads directly to the disruption of the Hsp90 activity and the chaperone complex functions, resulting in depletion of the oncogenic client proteins.
StressMarq Biosciences Inc has endeavored to provide a full series of unparalleled hsp90 reagents to allow further study of the Hsp90 chaperone system in vivo and in vitro. Although not exhaustive, the following table shows the unparalleled position StressMarq has created amongst suppliers.
Supplier: |
StressMarq
Biosciences Inc |
StressMarq
Biosciences Inc. Product Number |
Competitor A | Competitor
B |
| Antibodies |
||||
| Hsp90a | Yes | SMC-108, SMC-112, SMC-137, SMC-147 | Yes | Yes |
| Hsp90ß | Yes | SMC-107, SMC-136, SPC-177 | Yes | Yes |
| Hsp90 total | Yes | SMC-112, SMC-149, SPC-104 | Yes | Yes |
| Broadest species cross-reactivity, including insect cell Hsp90 | Yes | SMC-112 | No | No |
| Hsp90 complex isolation | Yes | SMC-109 | No | No |
| Proteins | ||||
| Hsp90a – Geldanamycin binding certified* | Yes | SPR-101 | No | No |
| Hsp90ß Geldanamycin binding certified* | Yes | SPR-102 | No | No |
| Hsp90ß – Endotoxin-free | Yes | SPR-102 | No | No |
| Hsp70 Endotoxin-free | Yes | SPR-117 | No | No |
| IHC Kits | ||||
| Hsp90a | Yes | SKT-243 | No | No |
| Hsp90ß | Yes | SKT-244 | No | No |
| Hsp90 total | Yes | SKT-245 | No | No |
| Inhibitors | ||||
| 17-AAG | Yes | SIH-100A | Yes | No |
| Geldanamycin | Yes | SIH-111A, B | Yes | No |
| Biotin- Geldanamycin | Yes | SIH-112A | No | No |
| FITC- Geldanamycin | Yes | SIH-113A | No | No |
| 17-DMAG | Yes | SIH-114A | No | No |
| 17-GMB-APA-GA | Yes | SIH-115A | No | No |
| Herbimycin A | Yes | SIH-116A, B | No | No |
| Radicicol | Yes | SIH-117A | No | No |
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Meet MJSBioLynx at the following events:
| Tradeshow | Location | Date |
| University of Alberta Supply Management
Show Our Sister Company, Chromatographic Specialties Inc. will also be in attendance. |
University of Alberta | May 7, 2009 |
|
Labfest
2009 Nearly every molecular biology lab in the country uses nucleic acid purification kits. Understanding the different technologies behind nucleic acid purification will give you the power and the tools necessary to use these products to their full potential. Presented by Dr. Björn Henze, Macherey-Nagel |
University of Toronto Residence | May 26 and 27, 2009 |
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