Microgenics Corporation

Discoverx Corporation

Boehringer Mannheim Gmbh

Riaz Rouhani

Gerald F Sigler

William A Coty

David Davoudzadeh

Rajendra Singh

Cynthia A Vistica

Peter Fung

Tabassum Naqvi

Inna Vainshtein

Anthony De Jesus Sanchez

Jeffrey E Shindelman

Paul R Morrill

David Davoudzaheh

Short enzyme donor fragments of &#x3b2;-galactosidase are provided of not more than 40 amino acids, where the short fragments are used as a label and may be substituted with a wide variety of organic compounds, particularly polypeptides having independent functional activity. The enzyme donor finds use in competitive and non-competitive assays, monitoring intracellular events, or other processes where a sensitive non-interfering label is desired.

Short enzyme donor fragment

The present invention provides a system for the improved detection of ecstasy-class compounds in biological samples. New ecstasy-class analogs are provided for detection of such ecstasy-class drugs. These analogs are compounds, or salts thereof, of a 2-amino-methylenedioxyphenyl (MDP) derivative attached to Z, where Z is a moiety capable of bonding, either directly or indirectly, with an immunogenic carrier, a detectable label, or a solid capture vehicle. Such analogs may be used to construct immunogens, enzyme or enzyme-donor conjugates, and other conjugates. The immunogens reproducibly generate antibodies with an exquisite ability to distinguish various ecstasy-class drugs in biological samples from potentially interfering substances. The specific antibodies and the conjugates may be used to distinguish and measure various ecstasy-class compounds in biological samples, such as those obtained from an individual suspected of substance abuse. In another aspect, the invention includes certain reagents, reagent combinations, and kits for performing assay methods for ecstasy-class compounds in a biological sample.

Ecstasy-class analogs and use of same in detection of ecstasy-class compounds

Systems, including methods and reagents, for identifying enzyme inhibitors. The systems employ a conjugate of a known inhibitor of a target enzyme and an enzyme donor, an enzyme acceptor that binds to the enzyme donor to form an active indicator-enzyme complex, and a detectable substrate for the indicator enzyme. The assay is performed by combining the candidate agent, the conjugate of the known inhibitor and enzyme donor, the enzyme acceptor, and the substrate under binding conditions, where the candidate compound competes with the conjugate for the target enzyme. By measuring the rate of product formation or substrate depletion catalyzed by the indicator enzyme, the inhibitory activity of the candidate compound can be determined. The methodology is particularly applicable for target enzymes that have substrates or products that are difficult to synthesize and/or detect, such as kinases and phosphatases.

Screening for enzyme inhibitors

Novel chemical analogs are disclosed for the essential heroin metabolite 6-O-acetyl morphine (6MAM). The analogs optionally can be made to contain protein reactive groups, and can be used to form protein conjugates, fluorescently labeled compounds, and solid-phase adsorbants. The proteins conjugates can be used in turn to raise antibodies reactive with 6MAM and having a low cross-reactivity with the closely related opiates, morphine and codeine. The antibodies can be used in combination with labeled analogs in exquisitely sensitive immunoassays suitable for testing for heroin abuse.

Non-hydrolyzable analogs of heroin metabolites suitable for use in immunoassay

To improve the detection of LSD in biological samples, antibodies are raised to LSD conjugated to a protein carrier, preferably through the indole ring. Selected antibodies are matched with an immunoassay reagent in which the LSD is conjugated in the same position to a labeling or separation means. The set of reagents can be used in immunoassays with remarkably little cross-reactivity with potential interfering substances such as chlorpromazine and ergotamine, and a low false-positive rate in a panel of clinical test samples. Also provided is a set of reagents for measuring glucuronide metabolites of LSD by immunoassay, which permits exposure to LSD to be determined over a longer diagnostic window.

Immunoassay reagents and methods for determination of LSD and LSD metabolites

Novel derivatives of LSD having the formula ##STR1## wherein R.sub.1 is an alkyl, cycloalkyl or aryl group having 1 to 10 carbon atoms, preferably an alkyl group having 1 carbon atom;

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Concord, CA, United States of America

Riaz Rouhani