University of California

Los Alamos National Security, LLC

The United States of America As Represented by the United States

Clifford J Unkefer

Rodolfo Antonio Martinez

Marc A Alvarez

Louis A Silks

Jurgen G Schmidt

Basil I Swanson

Paul J Jackson

Emmanuel Delhaize

Xuedong Song

Clement Furlong

Nigel J Robinson

Babetta L Marrone

Daniel J Simpson

Thomas W Whaley

Pat J Unkefer

Robert Atcher

William S Hlavacek

Fangping Mu

The reactivity of given metabolites is assessed using selected empirical atomic properties in the potential reaction center. Metabolic reactions are represented as biotransformation rules. These rules are generalized from the patterns in reactions. These patterns are not unique to reactants but are widely distributed among metabolites. Using a metabolite database, potential substructures are identified in the metabolites for a given biotransformation. These substructures are divided into reactants or non-reactants, depending on whether they participate in the biotransformation or not. Each potential substructure is then modeled using descriptors of the topological and electronic properties of atoms in the potential reaction center; molecular properties can also be used. A Support Vector Machine (SVM) or classifier is trained to classify a potential reactant as a true or false reactant using these properties.

Method for predicting enzyme-catalyzed reactions

The present invention is directed to the labeled compounds, wherein C* is each eitherC andC where at least one C* isC, each hydrogen of the methylene group is hydrogen or deuterium, the methyl group includes either zero or three deuterium atoms, Q is sulfide, sulfinyl, or sulfone, Z is an aryl group such as 1-naphthyl, substituted 1-naphthyl, 2-naphthyl, substituted 2-naphthyl, or a phenyl group wherein R, R, R, Rand Rare each independently either hydrogen, a C-Clower alkyl, a halogen, and an amino group such as NH, NHR and NRR' where R and R&#x2032; are each independently either a C-Clower alkyl, a phenyl, and an alkoxy group, and the methyl group can include either zero or three deuterium atoms. The present invention is also directed to the labeled compounds 

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The present invention is directed to labeled compounds of the formulae  wherein R, R, R, Rand Rare each independently selected from the group consisting of hydrogen, a C-Clower alkyl, a halogen, and an amino group selected from the group consisting of NH, NHR and NRR' where R and R&#x2032; are each independently selected from the group consisting of a C-Clower alkyl, an aryl, and an alkoxy group, and X is selected from the group consisting of hydrogen, a C-Clower alkyl group, and a fully-deuterated C-Clower alkyl group.

The present invention is directed to labeled compounds, of the formulae wherein C* is each independently selected from the group consisting ofC andC with the proviso that at least one C* isC, each hydrogen of the methylene group can independently be either hydrogen or deuterium, the methyl group includes either zero or three deuterium atoms, Q is from the group of sulfide, sulfinyl, and sulfone, Z is an aryl group from the group of 1-naphthyl, substituted 1-naphthyl, 2-naphthyl, substituted 2-naphthyl, and phenyl groups with the structure wherein R, R, R, Rand Rare each independently from the group of hydrogen, a C-Clower alkyl, a halogen, and an amino group from the group of NH, NHR and NRR' where R and R&#x2032; are each independently from the group of a C-Clower alkyl, a phenyl, and an alkoxy group, and the methyl group can include either zero or three deuterium atoms.

The present invention is directed to asymmetric chiral labeled glycerols including at least one chiral atom, from one to twoC atoms and from zero to four deuterium atoms bonded directly to a carbon atom, e.g., (2S) [1,2-C]glycerol and (2R) [1,2-C]glycerol, and to the use of such chiral glycerols in the preparation of labeled amino acids.

The present invention is directed to labeled compounds of the formulae  wherein R, R, R, Rand Rare each independently selected from the group consisting of hydrogen, a C-Clower alkyl, a halogen, and an amino group selected from the group consisting of NH, NHR and NRR' where R and R&#x2032; are each independently selected from the group consisting of a C-Clower alkyl, an aryl, and an alkoxy group, and X is selected from the group consisting of hydrogen, a C-Clower alkyl group, and a fully-deuterated C-Clower alkyl group. The present invention is also directed to a process of preparing labeled compounds, e.g., process of preparing [C]methacrylic acid by reacting a (CHCHO&#x2014;C(O)&#x2014;CH)&#x2014; aryl sulfone precursor withCHI to form a (CHCHO&#x2014;C(O)&#x2014;C(CH))&#x2014; aryl sulfone intermediate, and, reacting the (CHCHO&#x2014;C(O)&#x2014;C(CH))&#x2014; aryl sulfone intermediate with sodium hydroxide, followed by acid to form [C]methacrylic acid. The present invention is further directed to a process of preparing [H]methyl methacrylate by reacting a (HOOC&#x2014;C(CH)&#x2014; aryl sulfinyl intermediate with CDI to form a (HCOOC&#x2014;C(CH))&#x2014; aryl sulfinyl intermediate, and heating the(HCOOC&#x2014;C(CH))&#x2014; aryl sulfinyl intermediate at temperatures and for time sufficient to form [H]methyl methacrylate.

A sensor for the detection of tetrameric multivalent neuraminidase within a sample is disclosed, where a positive detection indicates the presence of a target virus within the sample. Also disclosed is a trifunctional composition of matter including a trifunctional linker moiety with groups bonded thereto including (a) an alkyl chain adapted for attachment to a substrate, (b) a fluorescent moiety capable of generating a fluorescent signal, and (c) a recognition moiety having a spacer group of a defined length thereon, the recognition moiety capable of binding with tetrameric multivalent neuraminidase.

Influenza sensor

Synthesis of &lsqb;2H1, 13C&rsqb;, &lsqb;2H2, 13C&rsqb; and &lsqb;2H3, 13C&rsqb;methyl aryl sulfones and sulfoxides

Synthesis of labeled oxalic acid derivatives

The present invention is directed to labeled compounds, &lsqb;2- C&rsqb;dithane wherein the C atom is directly bonded to one or two deuterium atoms. The present invention is also directed to processes of preparing &lsqb;2- C&rsqb;dithane wherein the C atom is directly bonded to one or two deuterium atoms. The present invention is also directed to labeled compounds, e.g., &lsqb; H , C&rsqb;methanol (arylthio)-, acetates wherein the C atom is directly bonded to exactly one or two deuterium atoms.

Synthesis of 2H- and 13C- substituted compounds

Synthesis of &lsqb;2H1, 13C&rsqb;, &lsqb;2H2, 13C&rsqb; and &lsqb;2H3, 13C&rsqb;methyl aryl sulfides

Synthesis of labeled metabolites

The present invention is directed to labeled compounds, &lsqb;2- C&rsqb;dithiane wherein the C atom is directly bonded to one or two deuterium atoms. The present invention is also directed to processes of preparing &lsqb;2- C&rsqb;dithiane wherein the C atom is directly bonded to one or two deuterium atoms. The present invention is also directed to labeled compounds, e.g., &lsqb; H , C&rsqb;methanol (arylthio)-, acetates wherein the C atom is directly bonded to exactly one or two deuterium atoms.

Growing community of inventors

Los Alamos, NM, United States of America

Clifford J Unkefer