Artist’s rendering of asymmetrically-branched carbohydrates on cell surface proteins.
Glycobiology is the study of glycans, the carbohydrate molecules that cover the surface of most human cells. Glycans attach to cell surface proteins and lipids, in a process called glycosylation. These cell surface structures are responsible for processes as varied at protein folding, cell signaling and cell-cell recognition, including sperm-egg recognition and immune cell interactions. Glycans play important roles in the red blood cell antigens that distinguish blood types O, A and B.
Opportunities in Glycomics Research
As more is learned about the role of glycans in cell communication, they are becoming important disease research targets, particularly the role of glycans in cancer and inflammatory diseases (2).
Some of the open questions surrounding glycans and glycosylation include glycan structural diversity. While some carbohydrates exist as straight or symmetrically branched chains, those populating the human glycome are asymmetrically branched, making them difficult to create and study in the laboratory (3). Continue reading
Kinase target engagement is a new way to study kinase inhibitors for target selectivity, potency and residency. The NanoBRET™ TE Intracellular Kinase Assays enable you to quantitate kinase-inhibitor binding in live cells, making these assays an exciting new tool for kinase drug discovery research.
For today’s blog about NanoBRET™ TE Intracellular Kinase Assay, we feature spokesperson Dr. Matt Robers. Matt is part of Promega’s R & D department and is one of the developers of the NanoBRET™ TE Intracellular Kinase Assay. Continue reading
Late in 2017, a group here at Promega launched an exciting new assay, the NanoBRET™ Target Engagement (TE) Intracellular Kinase Assay.
It’s easy for me to call this assay exciting; I was an editor on the project team. But judging by the reviews on the SelectScience® web site, others are excited about NanoBRET™ Target Engagement Intracellular Kinase Assay too.
A review of the NanoBRET TE Kinase assay from SelectScience® .
Finding the best inhibitor for your kinase doesn’t have to be a long trip.
A recent paper in Journal of Medicinal Chemistry, “Discovery of GDC-0853: A Potent, Selective and Noncovalent Bruton’s Tyrosine Kinase Inhibitor in Early Clinical Development” (1) details some elegant work in chemical modification and extensive testing during exploration of inhibitors for BTK. As a warmup to the article, here is a brief BTK backstory.
BTK (Bruton Tyrosine Kinase): Importance in Health and Disease
Bruton’s tyrosine kinase (BTK) was initially identified as a mediator of B-cell receptor signaling in the development and functioning of adaptive immunity. More recent and growing evidence supports an additional role for BTK in mononuclear cells of the innate immune system, especially dendritic cells and macrophages. For example, BTK functions in receptor-mediated recognition of infectious agents, cellular maturation and recruitment processes, and Fc receptor signaling. BTK has recently been identified as a direct regulator of a key innate inflammatory machinery, the NLRP3 inflammasome (2). Continue reading
The review “Kinase Inhibitors: the road ahead” was recently published in Nature Reviews Drug Discovery. In it, authors Fleur Ferguson and Nathanael Gray provide an up-to-date look at the “biological processes and disease areas that kinase-targeting small molecules are being developed against”. They note the related challenges and the strategies and technologies being used to efficiently generate highly-optimized kinase inhibitors.
This review describes the state of the art for kinase inhibitor therapeutics. To understand why kinase inhibitors are so important in the development of cancer (and other) therapeutics research, let’s start with the role of kinases in cellular physiology.
The road ahead for kinase inhibitor studies.
Why Kinases? Continue reading
Joins Nominees for Best New Drug Discovery & Development Product 2017
SelectScience® nominates NanoBRET™ Target Engagement Kinases Assay as a Best New Drug Discovery & Development product for 2017.
We were honored recently to have NanoBRET™ Target Engagement Intracellular Kinase Assays nominated by SelectScience® as one of the Best New Drug Discovery & Development Products of 2017. This is a Scientists’ Choice Award®, an opportunity for scientists like you worldwide to vote for your favorite new drug discovery/development product.
We are super excited about both the nomination and the NanoBRET™ Target Engagement Intracellular Kinase Assay. Here is a little information about the assay.
The Foundation for Food and Agriculture Research (FFAR) announced on November 30 that they are awarding $1M to a project based at the University of California, Davis, to study protein kinases of rice plants. The team is led by Dr. Pamela Ronald, a leading expert in plant genetics who has engineered disease- and flood-resistant rice. This project aims to address the growing agricultural problem of water scarcity by gaining a better understanding of the role kinases play in enabling drought-resistance. Promega will be supporting this research by providing NanoBRET™ products to help characterize kinase inhibitors.
Principal Investigator Pamela Ronald, Ph.D. Photo Credit: Deanne Fitzmaurice
The research team will begin by screening over 1,000 human kinase inhibitors to determine which ones do interact with the plant kinome and, if applicable, which kinase(s) they inhibit. Once the compound library has been established, the team will assess the inhibitors’ phenotypic effects on rice to identify kinases that, when inhibited, positively impact root growth and development. The long-term goal is to use these findings to engineer drought-resistant rice.
In his 2014 blog, “Why We Care About Glycosyltransferases” Michael Curtin, Promega Global Product Manager for Cell Signaling, wrote:
“Glycobiology is the study of carbohydrates and their role in biology. Glycans, defined as ‘compounds consisting of a large number of monosaccharides linked glycosidically’ are present in all living cells; They coat cell membranes and are integral components of cell walls. They play diverse roles, including critical functions in cell signaling, molecular recognition, immunity and inflammation. They are the cell-surface molecules that define the ABO blood groups and must be taken into consideration to ensure successful blood transfusions.
The process by which a sugar moiety is attached to a biological compound is referred to as glycosylation. Protein glycosylation is a form of post-translational modification, which is important for many biological processes and often serves as an analog switch that modulates protein activity. The class of enzymes responsible for transferring the sugar moiety onto proteins is called a glycosyltransferase (GT).”
Research surrounding drug discovery has historically been highly competitive and expensive. Unfortunately, many late-stage drug failures have occurred over recent years, often due to lack of efficacy. These failures have left the industry searching for new means by which to improve early drug discovery efforts aimed at understanding the drug target and its role in disease. One idea that is gaining traction is partnerships to openly share information at the early, precompetitive stages of drug discovery.
I used to think of open access only in terms of publishing data and information—online sites where you could freely access data without a subscription or membership, and without payment.
Structural Genomics Consortium logo.
Meet the Structural Genomics Consortium (SGC), the international partnership that’s taking open access to a new level in order to advance scientific research for scientists working in a variety of disciplines—structural genomics and beyond. The SGC might just become your new, best laboratory research partner. Continue reading
There is a lot riding on your luminescent assay results. Each plate represents precious time, effort and resources. Did you know that there are three things about your detection instrument that can impact how much useful information you get from each plate? Instruments with poor sensitivity may cause you to miss low-level samples that could be the “hit” you are looking for. Instruments with a narrow detection range limit the accuracy or reproducibility you needed to repeat your work. Finally, instruments that let the signal from bright wells spill into adjacent wells allow crosstalk to occur and skew experimental results, costing you time and leading to failed or repeated experiments. Continue reading