Cerus Corporation

Steritech, Inc.

University of Kentucky Research Foundation

Hans Peter Spielmann

Henry Rapoport

Stephen T Isaacs

Susan Wollowitz

Aileen Nerio

Douglas A Andres

Kareem A H Chehade

Kareem Abdel Hassan Chehade

Unnatural substrates of prenylation enzymens and antibodies that recognize unique moieties of prenylated proteins, which unique moieties are transferred from the unnatural substrates are used for detecting and isolating prenylated proteins, and for screening for inhibitors of prenylation enzymes.

Antibodies and unnatural substrates of prenylation enzymes for use in detecting and isolating prenylated proteins

Psoralen compound compositions are synthesized which have substitutions on the 4, 4&prime;, 5&prime;, and 8 positions of the psoralen, which yet permit their binding to nucleic acid of pathogens. Reaction conditions that photoactivate these bound psoralens result in covalent crosslinking to nucleic acid, thereby inactivating the pathogen. Higher psoralen binding levels and lower mutagenicity results in safer, more efficient, and reliable inactivation of pathogens. In addition to the psoralen compositions, the invention contemplates inactivating methods using the new psoralens.

Compounds for the photodecontamination of pathogens in blood

Method for photodecontamination of pathogens in blood using 5'-primary aminopsoralens

The present invention includes compositions comprising new psoralens with either a or primary amino substituent and a blood product that is suitable for in vivo use. The compositions are useful for the inactivation of pathogens in blood products such as platelets and plasma.

Psoralen compounds

The post-translational addition of a farnesyl moiety to the Ras oncoprotein is essential for its membrane localization and is required for both its biological activity and ability to induce malignant transformation. The present invention describes design and synthesis of a farnesylpyrophosphate (FPP) analog, 8-anilinogeranyl pyrophosphate (AGPP) that is transferred to Ras by farnesyltransferase (FTase), in which the &ohgr;-terminal isoprene unit of the farnesyl group has been replaced with an aniline functionality. AGPP potently inhibited FTase activity in vitro (IC,&equals;0.6 &mgr;M) and is highly selective showing little inhibitory activity against either geranylgeranyl-protein transferase type I (GGTase I) (IC,&equals;31 &mgr;M) or the utilization of FPP by the enzyme squalene synthase (IC,&equals;1000 &mgr;M). Kinetic analyses suggest that AGPP acts as a competitive inhibitor of FTase with respect to FPP. In vitro studies using &lsqb;,H&rsqb;AGPP show that the analog was appropriately transferred by FTase to Ras. Derivitization of AGPP with a bulky iodo group on the aniline ring does not significantly alter its biochemical properties. These data indicate that the modified molecules are the first truly transferable analogs of FPP and open the door to additional analogs to probe the biological function of protein farnesylation.

Farnesyl pyrophosphate analogs

The invention is directed to a novel compounds comprising 4-azidotetrafluoroaniline and the alkyl, acyl and sulfonamide derivatives thereof and to methods of making and using the same. The novel compounds are useful as a photoaffinity probe to study protein structure and function. Two methods for preparing 4-azidotetrafluoroaniline are disclosed, each employing a stable carbamate intermediate from which the 4-azidotetrafluoroaniline is derived.

Tetrafluoroazidoaniline and method of making and using the same

Psoralen compounds are synthesized which have substitutions on the 4, 4&prime;, 5&prime;, and 8 positions of the psoralen, which permit enhanced binding to nucleic acid of pathogens. Higher psoralen binding levels and lower mutagenicity are described, resulting in safer, more efficient, and reliable inactivation of pathogens in blood products. The invention contemplates inactivation methods using the new psoralens which do not compromise the function of blood products for transfusion. In particular, use of 5&prime;-primary aminoalkyl psoralens to inactivate pathogens in platelets is disclosed.

5&prime;-primary aminoalkyl psoralen compositions with platelets

Psoralen compounds are synthesized which have substitutions on the 4, 4&prime;, 5&prime;, and 8 positions of the psoralen, which permit enhanced binding to nucleic acid of pathogens. Higher psoralen binding levels and lower mutagenicity are described, resulting in safer, more efficient, and reliable inactivation of pathogens in blood products. The invention contemplates inactivation methods using the new psoralens which do not compromise the function of blood products for transfusion.

Methods for photodecontamination of pathogens in blood

Psoralen compounds are synthesized which have substitutions on the 4, 4', 5', and 8 positions of the psoralen, which permit enhanced binding to nucleic acid of pathogens. Higher psoralen binding levels and lower mutagenicity are described, resulting in safer, more efficient, and reliable inactivation of pathogens in blood products. The invention contemplates inactivation methods using the new psoralens which do not compromise the function of blood products for transfusion.

4'-primary aminopsoralen and platelet compositions

Psoralen compounds are synthesized which have substitutions on the 4, 4', 5', and 8 positions of the psoralen, which permit enhanced binding to nucleic add of pathogens. Higher psoralen binding levels and lower mutagenicity are described, resulting in safer, more efficient, and reliable inactivation of pathogens in blood products. The invention contemplates inactivation methods using the new psoralens which do not compromise the function of blood products for transfusion. In particular compounds with primary aminoalkyl substitutions on the 4' or 5' positions of psoralen are used to inactivate pathogens in blood products such as platelets.

Method for inactivation of pathogens in platelets using 4' and 5'

Psoralen compounds are synthesized which have substitutions on the 4, 4', 5', and 8 positions of the psoralen, which permit enhanced binding to nucleic acid of pathogens. Higher psoralen binding levels and lower mutagenicity are described, resulting in safer, more efficient, and reliable inactivation of pathogens in blood products. The invention contemplates inactivation methods using the new psoralens which do not compromise the function of blood products for transfusion. In particular, 4' and 5' primary aminoalkyl psoralens are photoactivated in platelet preparations to inactivate pathogens.

Method for the photoactivation of 4' and 5' primary aminoalkyl psoralens

Psoralen compound compositions are synthesized which have substitutions on the 4, 4', 5', and 8 positions of the psoralen, which yet permit their binding to nucleic acid of pathogens. Reaction conditions that photoactivate these bound psoralens result in covalent crosslinking to nucleic acid, thereby inactivating the pathogen. Higher psoralen binding levels and lower mutagenicity results in safer, more efficient, and reliable inactivation of pathogens. In addition to the psoralen compositions, the invention contemplates inactivating methods using the new psoralens.

Method for the photo-decontamination of pathogens in blood using

Psoralen compounds are synthesized which have substitutions on the 4, 4', 5', and 8 positions of the psoralen, which permit enhanced binding to nucleic acid of pathogens. Higher psoralen binding levels and lower mutagenicity are described, resulting in safer, more efficient, and reliable inactivation of pathogens in blood products. The invention compemplates inactivation methods using the new psoralens which do not compromise the function of blood products for transfusion. In particular, 5'-primary amino psoralens are photoactivated in order to inactivate pathogens in biological fluids.

Method of inactivating pathogens in biological fluids using

Psoralen compounds are synthesized which have substitutions on the 4,4',5', and 8 positions of the psoralen, which permit enhanced binding to nucleic acid of pathogens. Higher psoralen binding levels and lower mutagenicity are described, resulting in safer, more efficient, and reliable inactivation of pathogens in blood products. The invention contemplates inactivation methods using the new psoralens which do not compromise the function of blood products for transfusion. Also disclosed are compositions comprising 4' or 5'-primary amino substituted psoralens in a synthetic media.

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Lexington, KY, United States of America

Hans Peter Spielmann