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MEDFORD, MA, United States

Walvoort M.T.C.,Leiden University | Volbeda A.G.,Leiden University | Reintjens N.R.M.,Leiden University | Van Den Elst H.,Leiden University | And 4 more authors.
Organic Letters | Year: 2012

Well-defined fragments of hyaluronic acid (HA) have been obtained through a fully automated solid-phase oligosaccharide synthesis. Disaccharide building blocks, featuring a disarmed glucuronic acid donor moiety and a di-tert-butylsilylidene-protected glucosamine part, were used in the rapid and efficient assembly of HA fragments up to the pentadecamer level, equipped with a conjugation-ready anomeric allyl function. © 2012 American Chemical Society.

Walvoort M.T.C.,Leiden University | Van Den Elst H.,Leiden University | Plante O.J.,Ancora Pharmaceuticals, Inc. | Krock L.,Max Planck Institute of Colloids and Interfaces | And 4 more authors.
Angewandte Chemie - International Edition | Year: 2012

A big step towards routine: The title synthesis provides mannuronic acid alginate fragments featuring up to 12 cis-mannosidic linkages, in multi-milligram quantities (see scheme; Bn=benzyl, Lev=levulinoyl). Mannuronic acid building blocks were used in a second-generation carbohydrate synthesizer to secure the stereoselective introduction of the β-mannosidic bonds in a fully automated fashion. Copyright © 2012 WILEY-VCH Verlag GmbH & Co. KGaA, Weinheim.

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 530.98K | Year: 2009

DESCRIPTION (provided by applicant): Plasmodium falciparum malaria afflicts up to 10% of the global population, resulting in over 600 million infections and two to three million deaths annually. Malaria-related fatalities arise predominantly from two clinically defined complications associated with severe disease: cerebral malaria (CM) and severe malaria anemia (SMA). Substantial scientific evidence indicates that severe malarial disease results from the downstream effects of a toxin generated by the malaria parasite. This toxin, a glycolipid termed glycosylphosphatidylinositol (GPI), leads to excessive inflammatory cytokine production and, hence, the clinical manifestations observed in both CM and SMA. Published pre-clinical studies demonstrate that the glycan (carbohydrate) portion of the GPI can provide immunoprotection against CM caused by a malaria species within an established murine model. Recently, rodent models for SMA have been developed, which parallel the SMA clinically observed in humans upon malaria infection. Moreover, the models display one or both of the anemia forming mechanisms observed in human clinical disease: uninfected red blood cell clearance and erythropoietic suppression. The overall goals of this proposal are: to evaluate if immunization towards the GPI glycan can confer protection against SMA in the recently developed animal models, to identify a lead product candidate to move into development, and to begin to validate anemia as a potential clinical endpoint in detailed anemia characterization studies. PUBLIC HEALTH RELEVANCE: Ancora Pharmaceuticals Inc. is developing a novel vaccine against malaria. Severe anemia is a major complication due to malaria infection, especially in young children. This proposal aims to provide key proof-of-concept data that the anti-toxin vaccine approach may protect against severe malaria anemia.

Agency: Department of Health and Human Services | Branch: | Program: SBIR | Phase: Phase I | Award Amount: 130.75K | Year: 2004

DESCRIPTION (provided by applicant): Plasmodium falciparum malaria infects 5-10% of the global population (400 million clinical cases) and kills two million people annually. As such it ranks along with HIV and TB as the most serious infectious disease of

Scott A.E.,UK Defence Science and Technology Laboratory | Christ W.J.,Ancora Pharmaceuticals, Inc. | George A.J.,UK Defence Science and Technology Laboratory | Stokes M.G.M.,UK Defence Science and Technology Laboratory | And 7 more authors.
Bioconjugate Chemistry | Year: 2016

Melioidosis is an emerging infectious disease caused by Burkholderia pseudomallei and is associated with high morbidity and mortality rates in endemic areas. Antibiotic treatment is protracted and not always successful; even with appropriate therapy, up to 40% of individuals presenting with melioidosis in Thailand succumb to infection. In these circumstances, an effective vaccine has the potential to have a dramatic impact on both the scale and the severity of disease. Currently, no vaccines are licensed for human use. A leading vaccine candidate is the capsular polysaccharide consisting of a homopolymer of unbranched 1→3 linked 2-O-acetyl-6-deoxy-β-d-manno-heptopyranose. Here, we present the chemical synthesis of this challenging antigen using a novel modular disaccharide assembly approach. The resulting hexasaccharide was coupled to the nontoxic Hc domain of tetanus toxin as a carrier protein to promote recruitment of T-cell help and provide a scaffold for antigen display. Mice immunized with the glycoconjugate developed IgM and IgG responses capable of recognizing native capsule, and were protected against infection with over 120 × LD50 of B. pseudomallei strain K96243. This is the first report of the chemical synthesis of an immunologically relevant and protective hexasaccharide fragment of the capsular polysaccharide of B. pseudomallei and serves as the rational starting point for the development of an effective licensed vaccine for this emerging infectious disease. © Published 2016 by the American Chemical Society.

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