Latest News
20.10.2010
SARomics Biostructures provides key complex structures in a drug design project.
Press release
Lund, Sweden, October 20, 2010 – SARomics Biostructures is pleased to announce the publication of its latest scientific results. The paper, which highlights the work of SARomics Biostructures and its co-founder Prof. Mikael Akke describes state-of-the-art investigations of the fundamental driving forces behind drug binding to proteins.
Diehl et al. (2010) “Conformational entropy and protein flexibility in ligand design targeting the carbohydrate recognition domain of galectin-3” J. Am. Chem. Soc. 132, 14577-14589, (Open access; freely available).
SARomics Biostructures provided crystallization and structure determination services within this exciting project. High-resolution protein structures are a prerequisite for detailed investigations of drug binding in molecular terms. In the present project, SARomics Biostructures determined the crystal structure of the carbohydrate recognition domain of galectin-3 in complex with a designed ligand at a resolution of 1.20 Å. The high-resolution structure made it possible for our clients to interpret experimental data from nuclear magnetic resonance relaxation and thereby explore the role of protein conformational entropy in modulating drug–target affinity.
The β-galactoside-binding protein galectin-3 is involved in the regulation of apoptosis, intracellular trafficking, cell signalling and cell adhesion. It is a potential target for treatments of cancer and inflammation.
Reference:
Diehl C, Engström O, Delaine T, Håkansson M, Genheden S, Modig K, Leffler H, Ryde U, Nilsson UJ, Akke M. (2010). Protein flexibility and conformational entropy in ligand design targeting the carbohydrate recognition domain of galectin-3. J Am Chem Soc. 2010 Oct 20;132(41):14577-89.
View the paper (open access).
22.04.2010
SARomics researchers participate in the discovery that proteolysis of human thrombin generates host defense peptides.
Paper abstract
The coagulation system is characterized by the sequential and highly localized activation of a series of serine proteases, culminating in the conversion of fibrinogen into fibrin, and formation of a fibrin clot. Here we show that C-terminal peptides of thrombin, a key enzyme in the coagulation cascade, constitute a novel class of host defense peptides, released upon proteolysis of thrombin in vitro, and detected in human wounds in vivo. Under physiological conditions, these peptides exert antimicrobial effects against Gram-positive and Gram-negative bacteria, mediated by membrane lysis, as well as immunomodulatory functions, by inhibiting macrophage responses to bacterial lipopolysaccharide. In mice, they are protective against P. aeruginosa sepsis, as well as lipopolysaccharide-induced shock. Moreover, the thrombin-derived peptides exhibit helical structures upon binding to lipopolysaccharide and can also permeabilize liposomes, features typical of “classical” helical antimicrobial peptides. These findings provide a novel link between the coagulation system and host-defense peptides, two fundamental biological systems activated in response to injury and microbial invasion.
Read more »
06.04.2010
SARomics researchers co-authors on drug discovery paper describing an innovative structure-guided fragment selection approach. Read more »
11.01.2010
Today SARomics welcome Dr. Mattias Hansson who is the latest addition to our team. View Mattias profile on LinkedIn
Latest News
Press release
13.12.2010
Inimex Pharmaceuticals and SARomics Biostructures Announce Successful Achievement of Key Scientific Milestone in Structural Biology Collaboration
Vancouver, BC, Canada and Lund, Sweden, December 13, 2010 / Press release by b3c newswire / – Inimex Pharmaceuticals and SARomics Biostructures announce that they have achieved a scientific milestone in their collaboration to solve the structure of Inimex’s Innate Defense Regulator (IDR) IMX942 in complex with its target, the ZZ domain of human p62 (sequestosome-1). No structures were previously available for this challenging protein domain. The crystal structure determined by SARomics Biostructures provides invaluable information that will assist the functional understanding of IMX942 and the development of the new generation of IDRs.
The p62 ZZ domain was cloned, expressed, purified and crystallized by SARomics Biostructures in collaboration with their molecular biology partner Vectron Biosolutions in Trondheim, Norway. Excellent crystallographic data were obtained at the MAX-lab synchrotron in Lund, Sweden.
“We are very excited to be able to help Inimex Pharmaceuticals fully leverage the potential of IMX942 by revealing the molecular details of its interactions with its target protein”, says Dr. Derek Logan, Chief Scientific Officer of SARomics Biostructures AB.
About IMX942
IMX942 is the first of a new class of drugs known as Innate Defense Regulators (IDRs), which improve survival, ameliorate tissue damage and reduce bacterial infections through modulation of innate defenses. IMX942 is a small, proprietary, fully synthetic peptide that binds to the intracellular adaptor protein p62 and modifies the signaling network downstream of TLR, TNF, and IL-1 receptors. IMX942 acts on the final common pathways of pathogenesis, being effective against antibiotic resistant infections and controlling the outcome of disease caused by a broad spectrum of pathogens, by chemotherapy and by localized radiation.
About Inimex Pharmaceuticals - www.inimexpharma.com
Inimex Pharmaceuticals Inc. is a privately held biopharmaceutical company dedicated to the discovery and development of new medicines based on the selective modulation of the innate immune response. The Company’s first drug candidate, IMX942, has completed Phase 1 clinical studies in healthy volunteers and is in development for a number of indications, including control of disease in high-risk patients in the hospital setting. For more information, please visit www.inimexpharma.com.
For more information on IDR please view this paper:
Yu et al. (2009). J Biol Chem 284, 36007-36011.
Press release
20.12.2010
SARomics Biostructures and Vectron Biosolutions announce joint service offering
Lund, Sweden & Trondheim, Norway, December 20, 2010 – SARomics Biostructures and Vectron Biosolutions announced today that they have partnered to offer a joint service to the life science industry. This service will cover customized gene to structure projects and will utilize Vectron Biosolutions expertise in protein production and SARomics Biostructures expertise in protein crystallization and structure determination.
Recently, the two companies successfully executed their first gene-to-structure project and they have now formalized their collaboration. Vectron Biosolutions proprietary expression vector technology optimizes production of clients’ proteins and will make possible amounts suitable for crystallography even for proteins that normally are difficult to express. SARomics Biostructures has a strong track record of solving customers’ crystal structures and by combining the expertise from both companies the joint service will leverage their joint potential to meet clients’ structural biology needs.
“We are very pleased with this collaboration. Now we are able to execute gene-to- structure projects in an efficient way that our customers will benefit from”, says Dr. Derek Logan, Chief Scientific Officer of SARomics Biostructures AB.
“We are very excited to combine our innovative gene expression platform with SARomics’ expertise in protein structure determination, and are confident this will add greater value to our customers”, says Dr. Trond Erik Vee Aune, CEO of Vectron Biosolutions AS.
About Vectron Biosolutions
Through a combination of experienced life science researchers, state-of-the-art laboratory facilities, a proprietary technology platform and competent management, Vectron Biosolutions AS supplies the life sciences with superior technology and solutions. The company focuses on developing broad-host-range vector technology, especially expression vectors for industrial level production of recombinant proteins. In addition to providing innovative vector technology, Vectron Biosolutions AS offers its own life science research services, including recombinant protein production, vector development and molecular engineering of proteins and nucleic acids.
For more information, please visit www.vectronbiosolutions.com.