Abstract:
Inhibition of HIV-1 replication by disrupting the processing of the viral Gag capsid (CA) protein (p24) from the CA-spacer peptide 1 (SP1) protein precursor (p25) is disclosed. Amino acid sequences containing a mutation in the Gag p25 protein, with the mutation resulting in a decrease in the inhibition of processing of p25 to p24 by dimethylsuccinyl betulinic acid or dimethylsuccinyl betulin, polynucleotides encoding such mutated sequences and antibodies that selectively bind such mutated sequences are also included. Methods of inhibiting, inhibitory compounds and methods of discovering inhibitory compounds that target proteolytic processing of the HIV Gag protein are included. In one embodiment, such compounds inhibit the interaction of the HIV protease enzyme with Gag by binding to Gag rather than to the protease enzyme. In another embodiment, viruses or recombinant proteins that contain mutations in the region of the Gag proteolytic cleavage site can be used in screening assays to identify compounds that target proteolytic processing.
Abstract:
Methods for removal of positively charged microbicidal compound, in particular an aziridino compound, from composition such as a blood product by contacting the composition with a cation exchange resin allowing the positively charged compound to bind to the resin and then separating the resin-bound compound from the composition.
Abstract:
Methods are provided for treatment of diseases. The methods include preventing or inhibiting transcription and/or replication of a nucleic acid molecule by administering to a subject in need of such treatment an effective amount of one or more aziridino compounds. Pharmaceutical compositions comprising the one or more aziridino compounds also are provided.
Abstract:
The invention is based on the discovery of a method for removing an analyte from blood cells that results in a preparation of blood cells in which the level of the residual analyte is significantly reduced in the cell population. The method can be performed on large volume blood cell suspensions, and the cells prepared in this manner remain viable following prolonged storage and are suitable for therapeutic use, e.g. in transfusion applications. A preferred blood cell preparation is one that includes a red blood cell (RBC) population.
Abstract:
Disclosed is a method for identifying levels of an infectious virus in a cell population by comparing the level of a viral gene product in a first population of cells cultured in the presence of the virus with the level of the viral gene product in a second population of cells cultured under conditions that inhibit replication of the virus, e.g., cells that are cultured in the presence of an inhibitor of replication of the virus.
Abstract:
The invention features a method for inactivating parasites in biological compositions. The method includes contacting the biological composition with an aziridino compound under parasite inactivating conditions.
Abstract:
Betulin and dihydrobetulin acyl derivatives according to the present invention have been found to have potent anti-HIV activity. The compounds of the present invention have Formula I as described herein, or pharmaceutically acceptable salts thereof; wherein R 1 is a C 2 -C 20 substituted or unsubstituted carboxyacyl or ester thereof; R 2 is hydrogen, halogen, hydroxyl or -OR 3 , R 3 is C 2 -C 20 substituted or unsubstituted carboxyacyl; and R 4 is hydrogen or C(C 6 H 5 ) 3 ; wherein the dashed line represents an optional double bond between C20 and C29.
Abstract translation:已经发现根据本发明的桦木醇和二氢甜菜碱酰基衍生物具有有效的抗HIV活性。 本发明的化合物具有本文所述的式I或其药学上可接受的盐; 其中R 1是C 2 -C 20 - 取代或未取代的羧酰基或其酯; R 2是氢,卤素,羟基或-OR 3,R 3是C 2 -C 3 取代或未取代的羧酰基; 并且R 4是氢或C(C 6 H 5)3 N 3。 其中虚线表示C20和C29之间任选的双键。
Abstract:
Methods are provided for treatment of diseases. The methods include preventing or inhibiting transcription and/or replication of a nucleic acid molecule by administering to a subject in need of such treatment an effective amount of one or more aziridino compounds. Pharmaceutical compositions comprising the one or more aziridino compounds also are provided.
Abstract:
The invention is based on the discovery of a method for removing an analyte from blood cells that results in a preparation of blood cells in which the level of the residual analyte is significantly reduced in the cell population. The method can be performed on large volume blood cell suspensions, and the cells prepared in this manner remain viable following prolonged storage and are suitable for therapeutic use, e.g. in transfusion applications. A preferred blood cell preparation is one that includes a red blood cell (RBC) population.