Dear Colleagues

Happy Holidays and welcome to Emerald BioStructures' second e-Newsletter of 2010. The past six months have been exciting with a strong track record of collaborative deal making and publication of structural insights produced from these collaborations. We added a stellar new Scientific Advisory Board, improved our web site, and have hit key milestones in some of our biggest projects.

At Emerald we take pride in following the development path of compounds that benefited from structures generated by our research team. Emerald has been involved in the development of six different small molecules that are at IND or have gone into human clinical trials. These include three molecules for deCODE genetics, two for Deciphera Pharmaceuticals, and one for N30 Pharma.

Whether you're a current client, a former one, or simply interested in our latest developments, read on.

To accelerate your leads-development program, call our Business Development office today at 206-780-8959.
Lance Stewart, CEO

COLLABORATIONS

Through our world-class X-ray crystallography and structure-based design capabilities, we provide our clients with structural insight into target-ligand binding modes. We characterize protein-ligand interactions using all major assay and biophysical screening techniques (X-ray, NMR, SPR, ITC, and others). Our Fragments of Life™ technology for fragment based drug discovery has produced leads for a wide variety of targets.

Recent collaboration news includes:

• Michael J. Fox Foundation: Emerald recently announced that it is leading an international consortium to elucidate the X-ray crystal structure of the Leucine Rich Repeat 2 (LRRK2) protein kinase, a key protein involved in Parkinson's Disease. This multi-year effort is funded by the Michael J. Fox Foundation and leverages our extensive kinase experience and demonstrated ability to manage complex multi-site projects.
   
• Theraclone Sciences: We announced a collaboration with Theraclone Sciences to elucidate Antibody-Antigen co-crystal structures. This is an excellent example of a growing number of similar collaborations that Emerald will be announcing in coming months, and builds on our successfully published work in on mAb-epitope structures.
   
• SomaLogic: Building on a successful collaboration to elucidate the structures of protein targets bound to chemically modified DNA aptamers (SOMAmers), Emerald announced a strategic collaboration for the structure-based design of SOMAmers and small molecule therapeutics, based on co-crystal structures of selected targets bound to high affinity SOMAmers.
   
• Biogen Idec: Emerald announced the initiation of two new research collaborations with Biogen Idec, both of which provide Biogen Idec with access to Emerald's gene-to-structure pipeline, and experience with difficult protein targets, including the de novo determination of first crystal structure of a novel protein target.

CORPORATE UPDATES

Scientific Advisory Board
We are extremely pleased to expand the scientific expertise of our team with perspectives from our new Scientific Advisory Board (SAB). Our SAB members represent a diverse breadth of experience from academia, big pharma, and biotech. SAB members include:

John Hunt, Ph.D.
Assistant Professor at Columbia University, Biophysics and X-ray Crystallography leader in structural genomics and membrane proteins. A.B. Harvard University, Ph.D. Yale University, Postdoctoral Fellow, University of Texas Southwestern with Prof. Johann Deisenhofer .

Lynn Silver, Ph.D.
Thought leader on antibacterial drug discovery with 21 years at Merck in antibiotics research. Part of a team that discovered and launched INVANZ®. President and Founder of LL Silver Consulting, LLC. B.S. from Brandeis University, Ph.D. from Tufts University, Postdoctoral fellow at Université de Genève with Prof. Lucien G. Caro.

John Mulligan, Ph.D.
Founder and former CEO of Blue Heron Biotechnology (leading gene synthesis Co.), and prior positions at Darwin Molecular. B.S. from MIT, Ph.D. from Stanford, Daymon Runyan-Walter Winchell postdoctoral fellowship with Ron Davis at Stanford.

John McCall, Ph.D.
Thought leader in structure based drug design. President and Founder, PharMac LLC. Former Vice President and Global Head of Chemistry for both Pharmacia and Pharmacia & Upjohn and Vice President Research with Pfizer. Ph.D. from the University of Wisconsin, Postdoctoral Fellow at Harvard University with R.B. Woodward.

NMR Automation
We have completed installation of our new 500mHz NMR with automated sample handling for high throughput fragment/ligand screening and protein characterization. This new equipment installation will make Emerald the leading service provider of biophysical screening technologies for fragment based lead discovery, with fully integrated X-ray, NMR, and access to SPR.

270th Infectious Disease Structure Solved
Emerald recently solved the 270th novel infectious disease protein crystal structure within the Seattle Structural Genomics Center for Infectious Disease (SSGCID), a large collaboration with our colleagues at Seattle BioMed, the University of Washington, and Battelle Memorial Institute / Pacific Northwest National Laboratory. We are now solving 100+ crystal structures of novel infectious disease protein targets each year in this 5-year project, including several fragment and ligand bound target structures. SSGCID has already become one of the world's most productive structural genomics projects.

2010 PUBLICATIONS

2010 has been a stellar year for peer-reviewed publications of Emerald scientists’ work. We have published about a dozen papers, including a landmark paper on allosteric modulation of PDE4, which was the front cover story for the January 2010 issue of Nature Biotechnology. Key additional publications include:

Identifying regulators for EAG1 channels with a novel electrophysiology and tryptophan fluorescence based screen.
Brelidze TI, Carlson AE, Davies DR, Stewart LJ, Zagotta WN.
PLoS One. 2010 Sep 2;5(9). pii: e12523.

Scientists at Emerald BioStructures have co-authored a peer-reviewed article with University of Washington Professor William N. Zagotta that demonstrates an innovative use of the Emerald Fragments of Life™ ligand library to identify regulators for EAG1 channels. The work was published in PloS One, an open-access journal for the communication of peer-reviewed scientific and medical research.

Structural basis for the dual recognition of IL-12 and IL-23 by ustekinumab.
Luo J, Wu SJ, Lacy ER, Orlovsky Y, Baker A, Teplyakov A, Obmolova G, Heavner GA, Richter HT, Benson J.
J Mol Biol. 2010 Oct 8;402(5):797-812. Epub 2010 Aug 4.

Scientists at Centocor, in collaboration with Emerald BioStructures, have published the structure elucidation of interleukin-12 bound to the Fab portion of Ustekinumab, a fully human monoclonal antibody (mAb) that binds specifically to inflammatory cytokines IL-12/IL-23p40 and neutralizes human IL-12 and IL-23 bioactivity. The structure demonstrates ustekinumab binds to the same epitope on p40 in both IL-12 and IL-23, thus explaining its dual specificity.

Switch control pocket inhibitors of p38-MAP kinase. Durable type II inhibitors that do not require binding into the canonical ATP hinge region.
Ahn YM, Clare M, Ensinger CL, Hood MM, Lord JW, Lu WP, Miller DF, Patt WC, Smith BD, Vogeti L, Kaufman MD, Petillo PA, Wise SC, Abendroth J, Chun L, Clark R, Feese M, Kim H, Stewart L, Flynn DL.
Bioorg Med Chem Lett. 2010 Oct 1;20(19):5793-8. Epub 2010 Aug 3.

Scientists at Deciphera Pharmaceuticals and Emerald BioStructures have co-authored peer reviewed work describing the structures and binding modes of novel 'switch control pocket inhibitors' of p38-alpha kinase that trap the target in an inactive type II state. This work allowed Deciphera to gain key structural insights into the binding modes of their 'switch pocket inhibitors' of protein kinases.

Biological and structural characterization of a host-adapting amino acid in influenza virus.
Yamada S, Hatta M, Staker BL, Watanabe S, Imai M, Shinya K, Sakai-Tagawa Y, Ito M, Ozawa M, Watanabe T, Sakabe S, Li C, Kim JH, Myler PJ, Phan I, Raymond A, Smith E, Stacy R, Nidom CA, Lank SM, Wiseman RW, Bimber BN, O'Connor DH, Neumann G, Stewart LJ, Kawaoka Y.
PLoS Pathog. 2010 Aug 5;6(8). pii: e1001034.

Emerald scientists and members of the Seattle Structural Genomics Center for Infectious Disease (SSGCID), reported peer reviewed work from an international collaboration that describes how the H1N1 flu virus has used a new biochemical trick to spread efficiently in humans.

Nanovolume optimization of protein crystal growth using the microcapillary protein crystallization system.
Gerdts CJ, Stahl GL, Napuli A, Staker B, Abendroth J, Edwards TE, Myler P, Van Voorhis W, Nollert P, and Stewart LJ
J Appl Cryst (2010) 43:1078-1083

Emerald scientists published research demonstrating the powerful utility of their innovative award winning Microcapillary Protein Crystallization System for crystallization and structure determination of infectious disease protein targets.

Specific Btk inhibition suppresses B cell- and myeloid cell-mediated arthritis.
Di Paolo JA, Huang T, Balazs M, Barbosa J, Barck KH, Bravo BJ, Carano RA, Darrow J, Davies DR, Deforge LE, Diehl L, Ferrando R, Gallion SL, Giannetti AM, Gribling P, Hurez V, Hymowitz SG, Jones R, Kropf JE, Lee WP, Maciejewski PM, Mitchell SA, Rong H, Staker BL, Whitney JA, Yeh S, Young WB, Yu C, Zhang J, Reif K, Currie KS.
Nature Chemical Biology (2010) Nov. 28 [Epub ahead of print]. PMID: 21113169 [PubMed - as supplied by publisher]

As part of a collaboration with CGI Pharmaceuticals, Inc., Emerald scientists contributed two X-ray crystal structures of Bruton's tyrosine kinase (Btk) bound to key small molecule inhibitors. Emerald's work has allowed CGI and their partners to gain important chemical insight into specificity factors between a novel Btk inhibitor, CGI1746, and the reference compound dasatinib.

UPCOMING EVENTS

Connect with Emerald scientists at the following events:

CHI Peptalk
Jan 10-14, 2011

Keystone/ Transmembrane Signaling by GPCRs and Channels
Jan 23-28, 2011

Molecular Medicine Tri-Conference
Feb 23-25, 2011

WBBA NW Innovation
March 2-3, 2011

Fragments III 2011 - Third RSC-BMCS Fragment-based Drug Discovery meeting
March 7-8, 2011

ACS Spring Symposium 2011
March 27-31, 2011

Evolving Approaches to Early-Stage Drug Discovery
April 3-7, 2011

Encouraging Development of Therapeutics for Neglected Diseases
April 4-5, 2011

Drug Discovery Chemistry
April 12-14, 2011

PEGS Summit 2011
May 9-13

CONTACT US

Diana R. Wetmore, Ph.D.
Vice President of Business Development and Alliances
dwetmore@embios.com
206-780-8959

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