ÁÔÆæÖØ¿Ú

Education

BS, Fort Lewis College, Durango, CO

PhD, ÁÔÆæÖØ¿Ú State University, Bozeman, MT; Advisor Professor Tom Livinghouse

Courses Taught

CHMY 630

Research Interests

My research interest included the development off new methodology for the synthesis of immunomodulating compounds; the discovery of new, drugable, immunomodulating compounds and the determinatio of Mechanism of Action (MOA) and activation pathways of new compounds; the pharmaco kenetics of new drug substances; and process development of new synthetic immunomodulators for clinical application.

Projects

My research interests center on the discovery and developmetnt of immune modifying compounds for applications in vaccine research and treatment of autoimmune diseases. My experience allows my group to focus on everything from crystal structure assisted molecule design, library synthesis, SAR, synthetic route optimization and risk assesment and preclinical supply including PK/ADME determinations. We collaborate on a number of projects at various stages of development. I'm currently attempting, through a pilot grant and collaboration with CBSD, to elucidate specific binding motif required for activation of Toll Like Receptor 4 (TLR-4) through crystal structure determination of the TLR-4/MD2 complex with agonist CRX-527 and antagonist CRX-526. 

Since Joining UM in 2016 after 13 years at GlaxoSmithKline I have bee nthe principle author of three patent applications. One describing novel TLR-4 ligands and two describing new Mincle receptor agonists. My group collaborates with researchers around the country on new indications and treatments for flue, tubeculosis and bacterial infection with the research demonstrating application in many other diseases.

Some current funding includes:

• HHSN272200900008C/NO1-AI-8009 NIH/NIAID Adjuvant Development Program. 

The goal of this contract is development of new adjuvant for use in a Rapid Acting Vaccine for influenza virus

• HHSN272200900036C/N01-AI-90036 NIH/NAIAD Innate Immune Receptors and Adjuvant Discovery: Identification of Novel Th17 inducing CLR Agonists as Vaccine Adjuvants. 

My current work is focused on the discovery of novel C-type lectin receptor (CLR) agonits capable of eliciting a TH17 immune response for vaccine development against Mycobacterium tuberculosis. I am the project manager on BAA-NIAID-DAIT-NIHAI2013168. I am the primary author for two patent applications describing novel MINCLE active ligand scaffolds.

• HHSN266200400008C/N01-AI-40008 NIH/NIAID. Innate Immune Receptors and Adjuvant Discovery.

The goal of the program was to develop novel synthetic TLR4 agonists, the aminoakylglucosaminide phosphates, for use as mucosal adjuvant and inducer of innate protection of the airways against infectious challenge.

• Vaccine Adjuvant Discovery Program (VADP): Discovery of Novel Synthetic IL-1 Adjuvants

Publications

1. Ryter, K. T., et al. (2019). "Aryl Trehalose Derivatives as Vaccine Adjuvants for Mycobacterium tuberculosis." J Med Chem.
   Kendal Ryter and Tom Livinghouse, “[2-((Trimethylsilyl)methyl)prop-2-enyl]-lithium. A Versatile Reagent for the Synthesis of 2-Substituted Propenylsilanes” J. Org. Chem. 1997, 62, 4842-4844
2. Kendal Ryter and Tom Livinghouse, “Dichloro(2,2,2-trifluoroethoxy)oxovanadium(V). A Remarkably Effective Reagent for Promoting One-Electron Oxidative Cyclization and Unsymmetrical Coupling of Silyl Enol Ethers”J. Am. Chem. Soc. 1998, 120, 2658-2659
3. Peter R. Guzzo,*, Ronald N. Buckle, Ming Chou, Sean R. Dinn, Michael E. Flaugh, Anton D. Kiefer, Jr., Kendal T. Ryter, Anthony J. Sampognaro, Steven W. Tregay, and Yao-Chang Xu, Preparation of 8-Amido-2-dimethylamino-1,2,3,4-tetrahydro-2-dibenzofurans and Several Fluorinated Derivatives via [3,3]-Sigmatropic Rearrangement of O-Aryloximes, J. Org. Chem., 2002, 68, 770-778. https://www.ncbi.nlm.nih.gov/pubmed/12558398
4. Bazin, H.G., Bess, L.S, Livesay, M.T., Ryter, K.T., Johnson, C.L., Arnold, J.S., and Johnson, D.A., “New synthesis of glycolipid immunostimulants RC-529 and CRX-524”, Tetrahedron Lett., 2006, 47(13), 2087-2092
5. Bryan H. Norman, Timothy I. Richardson, Jeffrey A. Dodge, Lance A. Pfeifer, Gregory L. Durst, Yong Wang, Jim D. Durbin,a Venkatesh Krishnan, Sean R. Dinn, Shengquan Liu, John E. Reilly and Kendal T. Ryter, “Benzopyrans as selective estrogen receptor b agonists (SERBAs). Part 4: Functionalization of the benzopyran A-ring”, Bioorganic & Medicinal Chemistry Letters., 2007, 17, 5082-5085
6. Bazin H.G., Murray, T.J., Bowen, W.S., Mozaffarian, A., Fling, S.P., Bess L.S., Livesay M.T., Arnold J.S., Johnson C.L., Ryter K.T., Johnson C.L., Cluff C.W., Evans J.T., Johnson D.A. The ‘ethereal’ nature of TLR4 agonism and antagonism the AGP class of lipid A mimetics, Bioorg. Med. Chem. Lett., 2008, 18, 5350-5454
7. Didierlaurent, A. M., Collignon, C., Bourguignon, P., Wouters, S., Fierens, K., Fochesato, M., Dengouga, N., Langlet, C., Malissen, B., Lambrecht, B. N., Garcon, N., Van Mechelen, M., Morel, S. (acknowledgement: Ryter), Enhancement of Adaptive Immunity by the Human Vaccine Adjuvant AS01 Depends on Activated Dendritic Cells, J. Immunol. 2014, 193, 1920-1930
8. Khalaf, J. K., Bowen, W.S., Ryter, K.T., Bazin H.G., Evans J.T., Johnson D.A. Characterization of TRIF Selectivity in the AGP Class of Lipid A Mimetics: Role of Secondary Lipid Chains, Bioorg. Med. Chem. Lett. 2015, 25(3), 547-553. http://www.ncbi.nlm.nih.gov/pubmed/25553892
9. Alyson J Smith,  Shannon Miller,  Cassandra Buhl,  Robert Child,  Margaret Whitacre,  Roman Schoener,  George Ettenger, David Burkhart,  Kendal Ryter and  Jay T Evans.  Species-specific structural requirements of alpha-branched trehalose diester Mincle agonists. Front. Immunol. - Vaccines and Molecular Therapeutics. Submitted on: 26 Jun 2018. 
10. Smith AJ, Graves B, Child R, Rice PJ, Ma Z, Lowman DW, Ensley HE, Ryter KT, Evans JT, Williams DL. Immunoregulatory Activity of the Natural Product Laminarin Varies Widely as a Result of Its Physical Properties. J Immunol. 2018 Jan 15;200(2):788-799. PubMed PMID: ; PubMed Central PMCID: . http://www.jimmunol.org/content/jimmunol/early/2017/12/15/jimmunol.1701258.full.pdf
11. Smith, A. J., et al. (2019). "Species-Specific Structural Requirements of Alpha-Branched Trehalose Diester Mincle Agonists." Frontiers in Immunology 10: 338.
12. Ryter, K. T., et al. (2019). "Aryl Trehalose Derivatives as Vaccine Adjuvants for Mycobacterium tuberculosis." J Med Chem. Publication Date:December 6, 2019
13. Rasheed, O. K., et al. (2020). "6,6′-Aryl trehalose analogs as potential Mincle ligands." Bioorg Med Chem 28(14): 115564. 
14. William R. Bartlett, Javier Read de Alaniz, Janet L. Carlson, Maria P. Dillon, Eric Edstrom, Derek A. Fischer, Adam A Goldblum, Gregory R. Luedtke, Gregory W. Paneitz, Kendal Ryter, Mark Schulz, Donnie A. Shepard, Christopher Switzer. Stereocontrolled Synthesis of (±)-Grandisol Synthesis 2022; 54(14): 3209-3214.

Affiliations

American Chemical Society

Specialized Skills

Mass spectrometry, synthetic chemistry, process safety, project management, cGMP and ICH-Q7A guidelines, contract manufacturing 

Professional Experience

Building on my extensive experience and training in Discovery Chemistry, Process Development chemistry and controlled environments first at Albany Molecular Research (Now Curia) and then GSK I have joined with three highly motivated and skilled scientists to found Inimmune. As a critical component of our success I was instrumental in the discovery of a new class of Toll Like Receptor 4 (TLR-4) ligands that are at the core of our companies technology platform. With more than 21 years of chemical synthesis experience, including Management of cGMP processes of products destined for clinical and commercial applications, I'm more than qualified to guide our portfolio through pre-clinical development to clinical and commercial readiness. Our teams experience and focus on products done right the first time will ensure success and confidence in our capabilities. I am passionate about bringing novel ideas from conception to fruition and I understand the hurdles that are required for the journey. My areas of expertise include: Chemical synthesis, discovery of novel adjuvants and adjuvant systems, process development and technology transfer, pilot scale synthesis, cGMP synthesis, analytical chemistry, cGMP requirements, QbD approaches, medicinal organic chemistry, immunotherapeutics and vaccines R&D.