Pyrophosphate Analog HIV-1 Reverse Transcriptase Inhibitors

The invention relates to compounds that inhibit HIV-1 DNA synthesis mediated by reverse transcriptase (RT). HIV-1 DNA synthesis by RT utilizes deoxynucleoside 5’-triphosphate (dNTP) as substrate and like many other enzymes, the reaction is reversible. Pyrophosphate analogs like imidodiphosphate strongly promote reverse reaction dNTP products containing the imidodiphosphate group instead of the naturally occurring pyrophosphate group. This imidodiphosphate-containing dNTP was found to be a potent inhibitor of the forward RT reaction.

Therapeutic and Diagnostic Targets for Severe RSV Infection

Respiratory Syncytial Virus (RSV) infects nearly all children by their second birthday. RSV usually causes mild respiratory illness, however, a subset of patients experience severe infection that require hospitalization. Successful host defense against viral pathogens requires rapid recognition of the virus and activation of both innate and adaptive immunity. Toll-Like Receptors (TLRs) are responsible for mounting an innate immune response and genetic variations within TLRs modulate severity of infection.

Reducing Bloodstream Neutrophils as a Treatment for Lung Infection and Inflammation

During lung infection, bloodstream neutrophils (PMNs) responding to infection travel to the airspace lumen. Although successful arrival of microbicidal PMNs to the airspace is essential for host defense against inhaled pathogens, excessive accumulation of PMNs in the lung contributes to the pathogenesis of several prevalent lung disorders, including acute lung injury, bronchiectasis, and COPD. Unfortunately, there is no treatment for controlling PMN accumulation in the lung.

Development of Reagents to Examine the Expression and Function of CYP2J Subfamily P450s

Cytochrome P450s catalyze the metabolism of a wide range of exogenous compounds, including drugs, industrial chemicals, environmental pollutants, and carcinogens. The 2C family of cytochrome P450 metabolizes an extensive number of drugs which include tolbutamide, S-Warfarin, mephenytoin, diazepam and taxol. The inventors cloned the cDNAs for several different CYP2J subfamily members including human CYP2J2, rat CYP2J3, mouse CYP2J5, mouse CYP2J6, and mouse CYP2J9. The recombinant proteins were expressed in insect cells.

Diagnostics and Therapeutics for Hydrocephalus

Congenital hydrocephalus is a significant public health problem, affecting approximately one in 500 live births in the United States. Congenital hydrocephalus has an adverse effect on developing brain and may persist as neurological defects in children and adults. Some of these defects may manifest as mental retardation, cerebral palsy, epilepsy and visual disabilities. Improved diagnostics are needed for assessing the risks of developing this debilitating disease.

Isolation of Hybridomas Producing Monoclonal Antibodies (MAbs) Inhibitory to Human CYP2J2

The National Institutes of Health announces three specific monoclonal antibodies that strongly inhibit and/or immunoblot the human cytochrome P450 2J2 (CYP2J2).

Cytochrome P450s catalyze the NADPH-dependent oxidation of arachidonic acid to various eicosanoids found in several species. The eicosanoids are biosynthesized in numerous tissues including pancreas, intestine, kidney, heart and lung where they are involved in many different biological activities.

A Tet-Regulated Mouse Model for Cataract

Cataract is the most common cause of blindness worldwide, with an estimated 25 million blind and 119 million visually impaired individuals worldwide. Over 20 million adults in the US alone are currently diagnosed with cataracts making this disease a major health concern. The incidence of cataract increases with age and a number of etiologic factors have been proposed in the pathogenesis of age-related cataract in humans including genetic factors, environmental factors and metabolic and biochemical changes in the crystalline lens.

Apparatus for Cryogenic-Electron Microscopy Sample Preparation

Cryo-Electron Microscopy (cryo-EM) is used to obtain high-resolution structural images of macromolecular structures. Samples must be purified and loaded onto cryo-EM grids before imaging. The ideal cryo-EM grid consists of particles that are evenly and richly distributed in a broad distribution of orientations throughout the holes of the support film. Current techniques to prepare cryo-EM grids are performed manually and require trial and error, resulting in a bottleneck in cryo-EM workflows.

Peanut therapeutics and diagnostics to treat severe food allergies

Up to 10% of the US population suffers from food allergies, with more than 40% of those experiencing life-threatening anaphylaxis. Peanut is one of the most common food allergens that give rise to persistent IgE-mediated food allergy. Oral immunotherapy (OIT) is used to reduce sensitivity to an allergen through repeated, small-dose exposure to the allergen. However, only a subset of patients develop a sustained response to the allergen and OIT carries notable side effects. 

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