SomaLogic and Emerald Bio publish first crystal structure of a SOMAmer bound to its target
Bedford MA and Boulder CO – November 5, 2012
The molecular structure of a SOMAmer (Slow Off-rate Modified Aptamer) reagent bound to its specific protein has been revealed for the first time by a team of scientists from Emerald Bio and SomaLogic in a manuscript published online this week in the Proceedings of the National Academy of Science (PNAS). Their analyses demonstrate the molecular basis for the vast improvement in protein binding by SOMAmers as compared to traditional aptamers, emphasizing that SOMAmers represent an entirely new class of molecular “affinity reagents” with multiple useful applications in life sciences and medicine.
“The structure of a SOMAmer bound to platelet-derived growth factor B (PDGF-BB) is only the first ‘glimpse’ into the astonishing array of novel molecular shapes that can be achieved by the SOMAmer technology” said Doug Davies, Senior Project Leader at Emerald Bio. “And it potentially represents an entirely new approach for studying and crystallizing difficult proteins.”
SOMAmers are based on traditional aptamers, short single strands of nucleic acids with specific folded shapes that can bind proteins and other biomolecules. However, the nucleotides used to make SOMAmers are modified by the addition of protein-like “side-chains” to the nucleotide bases themselves, which exponentially increases the number of unique shapes, as well as the binding affinity and specificity of each SOMAmer for its particular protein target.
“We have already demonstrated the huge advantages of SOMAmers for expanding the range of protein targets previously inaccessible to traditional aptamers. The current study with our colleagues at Emerald has now provided us with a clear structural basis of those advantages at a molecular level” said Nebojsa Janjic, Chief Science Officer of SomaLogic. “This work is a compelling demonstration of the enormous potential of SOMAmers as both diagnostic reagents and therapeutics.”
SomaLogic has developed more than 1500 SOMAmer reagents to date, with over 1100 of those already being used (in a multiplex assay called “SOMAscan™”) in biomarker discovery, drug discovery and development, and life sciences. In addition, several individual SOMAmers are under development as potential therapeutic molecules in their own right. These applications are underway both at SomaLogic and in partnership with leading biopharmaceutical and clinical diagnostic companies.
Several other SOMAmer-protein pair structures have been analyzed in addition to the SOMAmer — PDGF-BB structure described in the PNAS article published today, all demonstrating the unique properties and utility of this new class of binding reagent.
The PNAS article, entitled “Unique Motifs and Hydrophobic Interactions Shape the Binding of Modified DNA Ligands to Proteins Targets” by D.R. Davies et al., will be published the week of November 5, 2012. Once published, the entire manuscript can be accessed at: http://www.pnas.org/cgi/doi/10.1073/pnas.1213933109.
About Emerald Bio
Emerald Bio is a contract research organization that provides collaborative drug discovery services to pharmaceutical companies, biotechnology companies, academic institutions, and government facilities. Emerald is developing new technologies to study difficult proteins including the engineered expression, protein production and crystal structure determination of GPCRs and integral membrane proteins. The company operates a high-throughput platform leveraged for fragment-based lead discovery and structure-based drug design.
SomaLogic, Inc., is a privately held biomarker discovery and clinical diagnostics company based in Boulder, Colorado. The company’s mission is to use its proprietary proteomic technology to develop enhanced protein analysis tools and reagents for the life sciences community, to facilitate biomarker discovery and validation for diagnostic and therapeutic applications, and to develop and commercialize clinical diagnostic products that will improve the delivery of healthcare by offering timely and accurate diagnostic information to physicians and their patients. Further information about SomaLogic can be found at http://test.somalogic.com.
SomaLogic’s proprietary SOMAscan™ proteomic technology platform underlies a rapidly growing number of new diagnostic and therapeutic opportunities. The power of the SOMAscan platform comes from its use of a new generation of nucleic acid-based protein-binding reagents, called SOMAmers™ (Slow Off-rate Modified Aptamers). The unique physical properties of SOMAmers empower the accurate detection and measurement of thousands of proteins over a wide range of concentrations in small volumes of biological samples, all in a single SOMAscan assay.