Dsm IP Assets B.v.

Ecole Polytechnique Federale De Lausanne

Sanofi

New England Biolabs, Inc.

Covalys Biosciences Ag

Maik Kindermann

Stephane Duval

Kai Peter Johnsson

Alexandre Juillerat

Arnaud Gautier

Florent Beaufils

Anja Globisch

Irmgard Immig

Gilbert Weber

Markus Schwab

Hughes Jaccard

India Christina Sielaff

Christoph Bieri

The present invention relates to the field of reduction of methane emission in ruminants. Particularly, it relates to the use of a feed composition or a feed additive comprising at least one fatty acid containing at least 5 carbon atoms and at least one organic molecule substituted at any position with at least one nitrooxy group, for reducing the production of methane emanating from the digestive activities of ruminants, and/or to improve the ruminant performance.

Use of a feed composition for reducing methane emission in ruminants, and/or to improve ruminant performance

The present invention relates to the field of reduction of methane emission in ruminants. Particularly, it relates to the use of a feed composition or a feed additive comprising at least one antibiotic and at least one organic molecule substituted at any position with at least one nitrooxy group for reducing the production of methane emanating from the digestive activities of ruminants, and/or to improve the ruminant performance.

The present invention relates to a method for reducing the production of methane emanating from the digestive activities of a ruminant and/or for improving ruminant animal performance by using, as active compound at least one organic molecule substituted at any position with at least one nitrooxy group, or a salt thereof, which is administrated to the animal together with the feed. The invention also relates to the use of these compounds in feed and feed additives such as premix, concentrates and total mixed ration (TMR) or in the form of a bolus.

Use of nitrooxy organic molecules in feed for reducing methane emission in ruminants, and/or to improve ruminant performance

The present invention relates to a method for reducing the production of methane emanating from the digestive activities of a ruminant and or for improving ruminant animal performance by using, as active compound at least one nitrooxy alkanoic acid and/or derivative thereof, which is administrated to the animal together with the feed. The invention also relates to the use of these compounds in feed and feed additives such as premix, concentrates and total mixed ration (TMR) or in the form of a bolus.

Nitrooxy alkanoic acids and derivatives thereof in feed for reducing methane emission in ruminants, and/or to improve ruminant performance

The present invention relates to molecular probes of the formula (I){L1-R1-L}-A-CO&#x2014;NH&#x2014;R2-L2&#x2003;&#x2003;(I)as defined herein that allow for the observation of the catalytic activity of a selected cathepsin in in vitro assays, in cells or in multicellular organisms, a method for their preparation and the use thereof.

Imaging probes

The invention relates to new proteins called alkylcytosine transferases (ACTs) derived from O-alkylguanine-DNA alkyltransferase, and to substrates for ACTs specifically transferring a label to these ACTs and to fusion proteins comprising these. The substrates according of the invention are substituted cytosines of formula (I) wherein Ris an aromatic or a heteroaromatic group, or an optionally substituted unsaturated alkyl, cycloalkyl or heterocyclyl group with the double bond connected to OCH&#x2014;; Ris a linker; and L is a label or a plurality of same or different labels. The invention further relates to methods of transferring label L from these substrates of formula (I) to ACTs and ACT fusion proteins. The system of ACT-compound of formula (I) is particularly suitable for double labelling studies together with the known system O-alkylguanine-DNA alkyltransferase (AGT)-benzylguanines.

Labelling of fusion proteins with synthetic probes

The invention relates to new proteins called alkylcytosine transferases (ACTs) derived from O-alkylguanine-DNA alkyltransferase, and to substrates for ACTs specifically transferring a label to these ACTs and to fusion proteins comprising these. The substrates according of the invention are substituted cytosines of formula (I) wherein Ris an aromatic or a heteroaromatic group, or an optionally substituted unsaturated alkyl, cycloalkyl or heterocyclyl group with the double bond connected to OCH&#x2014;; Ris a linker; and L is a label or a plurality of same or different labels. The invention further relates to methods of transferring label L from these substrates of formula (I) to ACTs and ACT fusion proteins. The system of ACT-compound of formula (I) is particularly suitable for double labelling studies together with the known system O-alkylguanine-DNA alkyltransferase (AGT)-benzylguanines. 

The invention relates to pyrimidines suitable as substrates for O-alkylguanine-DNA alkyltransferases (AGT) of formula (I) wherein Ris hydrogen, lower alkyl, halogen, cyano, trifluoromethyl or azido; Ris a linker; and L is a label or a plurality of same or different labels. The invention further relates to methods of transferring a label from pyrimidines of formula (I) to O-alkylguanine-DNA alkyltransferases (AGT) and AGT fusion proteins.

Pyrimidines reacting with O6-alkylguanine-DNA alkyltransferase fusion protein and method for detecting protein

The invention relates to substrates for O-alkylguanine-DNA alkyltransferases (AGT) of formula R-A-X&#x2014;CH&#x2014;R&#x2014;R-L, wherein A is a group recognized by AGT as a substrate, X is oxygen or sulfur, Ris a group &#x2014;R-Lor a group R, Rand Rare, independently of each other, a linker, Ris an aromatic or a heteroaromatic group, or an optionally substituted unsaturated alkyl, cycloalkyl or heterocyclyl group with the double bond connected to CH, Ris arylmethyl or heteroarylmethyl or an optionally substituted cycloalkyl, cycloalkenyl or heterocyclyl group, Lis a label, a plurality of same or different labels, a bond connecting Rto A forming a cyclic substrate, or a further group &#x2014;R&#x2014;CH&#x2014;X-A-R, and Lis a label or a plurality of same or different labels. The invention further relates to methods of transferring a label from these substrates to O-alkylguanine-DNA alkyltransferases (AGT) and AGT fusion proteins.

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The invention relates to compounds of formula 1 wherein R-Ris a guanine derivative; X is oxygen or sulfur; Ris a heteroaromatic, unsaturated heterocyclyl or an alkynyl group with the double or triple bond connected to CH; Ris a linker; and L is a label, a plurality of same or different labels, a bond connecting Rto Rforming a cyclic substrate, or a further group &#x2014;R&#x2014;CH&#x2014;X&#x2014;R-R. The invention relates also to methods of manufacture of such novel AGT substrates, to intermediates useful in the synthesis of such AGT substrates, and to a method of transferring a label from such AGT substrates to O-alkylguanine-DNA alkyltransferase (AGT) fusion proteins comprising proteins of interest.

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Frankfurt-am-Main, Germany

Maik Kindermann