Abstract: The invention provides compounds that modulate the activity of protein kinases that are associated with human diseases, disorders, and conditions. In particular, compounds of the invention inhibit LRRK2.

Abstract: The invention provides compounds that modulate the activity of protein kinases that are associated with human diseases, disorders, and conditions. In particular, compounds of the invention inhibit LRRK2.

Abstract: The invention provides compounds that modulate the activity of protein kinases that are associated with human diseases, disorders, and conditions. In particular, compounds of the invention inhibit LRRK2.

Abstract: The invention provides compounds that modulate the activity of protein kinases that are associated with human diseases, disorders, and conditions. In particular, compounds of the invention inhibit TYK2, a member of the Janus Kinase (JAK) family of non-receptor protein kinases.

Abstract: Disclosed are compositions and methods for amplification of nucleic acid sequences of interest with greater efficiency and fidelity. The disclosed method relates to isothermal amplification techniques, such as Multiple Displacement Amplification (MDA), where the generation of DNA artifacts is decreased or eliminated. Generally, this can be accomplished by carrying out the reaction at elevated temperature. In particularly useful embodiments of the method, sugars and/or other additives can be used to stabilized the polymerase at high temperature. It has been discovered that generation of high molecular weight artifacts, in an isothermal amplification procedure, is substantially reduced or eliminated while still allowing the desired amplification of input DNA by carrying out the reaction at a higher temperature and, optionally, in the presence of one or more additives.

Abstract: A method is disclosed in which circular DNA molecules are amplified preferentially in a mixture of circular DNA molecules and linear DNA molecules by the inclusion of single strand DNA binding protein.

Abstract: The present invention provides methods, formulation and kits for the synthesis of long nucleic acid fragments. An improved PCR method is provided for amplifying long DNA fragments. In particular, a single thermostable DNA polymerase is used for the rapid amplification of over 10 kb long DNA fragments. Also provided is a method for extending long complementary DNA strands using this single enzyme formulation.

Abstract: Improved processes for the amplification of target DNA sequences in the form of single or double stranded circular DNA molecules, especially those present in colony and plaque extracts, using multiple specific and/or random sequence oligonucleotide primers are disclosed. The product of this amplification is used for analysis by restriction enzyme digestion or DNA sequencing and other analyses that involve hybridization. Kits containing components for use in the method are also described. Also described are further uses of this amplified DNA in sequencing, genotyping and haplotyping, and other molecular biology applications.

Abstract: The present invention provides methods, formulation and kits for the synthesis of long nucleic acid fragments. An improved PCR method is provided for amplifying long DNA fragments. In particular, a single thermostable DNA polymerase is used for the rapid amplification of over 10 kb long DNA fragments. Also provided is a method for extending long complementary DNA strands using this single enzyme formulation.

Abstract: Disclosed are compositions and methods for detecting small quantities of analytes such as proteins and peptides. The method involves associating a DNA circle with the analyte and subsequent release and rolling circle replication of the circular DNA molecule. In the method, an amplification target circle is associated with analytes using a conjugate of the circle and a specific binding molecule that is specific for the analyte to be detected. Amplification target circles not associated with the proteins are removed, the amplification target circles that are associated with the proteins are decoupled from the specific binding molecule and amplified by rolling circle amplification. The amplification is isothermic and can result in the production of a large amount of nucleic acid from each primer. The amplified DNA serves as a readily detectable signal for the analytes.

Abstract: The present disclosure provides a composition for enhancing effect of an inhibitor in inhibiting NAD+/NADP+ or NADH/NADPH dependent enzymes. The inhibition of the NAD+/NADP+ or NADH/NADPH dependent enzymes such as Enoyl-ACP reductase (ENR) by the composition of the present disclosure serves as a target for treating malaria and other infectious diseases. The present disclosure provides composition comprising inhibitor and polyphenol, wherein the polyphenol was found to enhance the inhibitory activity of the inhibitor. The present disclosure provides method for treating an infectious disease comprising administering an effective amount of the composition of the present disclosure to patients in need thereof.

Abstract: The current invention presents enoyl-ACP reductase, an enzyme of the type II fatty acid synthesis pathway as a target for treating human malarias and other infectious diseases. We also present in the current invention, 2-thioxothiazolidin-4-ones as antimicrobial and antimalarial agents. We provide 2-thioxothiazolidin-4-ones as antimicrobial and antimalarial agents either alone or in combination with other known antimicrobial and antimalarial agents with or without added adjuvants or diluents or carriers.

Abstract: Disclosed are compositions and methods for amplification of RNA molecules. The disclosed method involves synthesizing first strand cDNA molecules from RNA molecules, circularizing the first strand cDNA molecules and replicating the circularized first strand cDNA molecules using rolling circle replication. The method can be aided by the use of specialized primers for cDNA synthesis and specialized probes for circularizing the first strand cDNA molecules. The method can be used to replicate and amplify multiple RNA molecules, such as all RNA molecules in a sample or all mRNA molecules in a sample, or be used to replicate and amplify specific RNA molecules. Rolling circle replication of the circularized first strand cDNA molecules results in long DNA strands containing tandem repeats of the cDNA sequence. The tandem sequence DNA can be used directly (for detection of sequences, for example), further amplified, or used any other purpose.

Abstract: Disclosed are compositions and methods for amplification of RNA molecules. The disclosed method involves synthesizing first strand cDNA molecules from RNA molecules, circularizing the first strand cDNA molecules and replicating the circularized first strand cDNA molecules using rolling circle replication. The method can be aided by the use of specialized primers for cDNA synthesis and specialized probes for circularizing the first strand cDNA molecules. The method can be used to replicate and amplify multiple RNA molecules, such as all RNA molecules in a sample or all mRNA molecules in a sample, or be used to replicate and amplify specific RNA molecules. Rolling circle replication of the circularized first strand cDNA molecules results in long DNA strands containing tandem repeats of the cDNA sequence. The tandem sequence DNA can be used directly (for detection of sequences, for example), further amplified, or used any other purpose.

Abstract: Disclosed are compositions and methods for amplification of nucleic acid sequences of interest with greater efficiency and fidelity. The disclosed method relates to isothermal amplification techniques, such as Multiple Displacement Amplification (MDA), where the generation of DNA artifacts is decreased or eliminated. Generally, this can be accomplished by carrying out the reaction at elevated temperature. In particularly useful embodiments of the method, sugars and/or other additives can be used to stabilized the polymerase at high temperature. It has been discovered that generation of high molecular weight artifacts, in an isothermal amplification procedure, is substantially reduced or eliminated while still allowing the desired amplification of input DNA by carrying out the reaction at a higher temperature and, optionally, in the presence of one or more additives.

Abstract: The present invention provides a novel method for ligation of oligonucleotides containing 5′-phosphorothioates on complementary templates by the action of DNA ligases. This reaction is readily applied to the synthesis of a single stranded circular DNA containing a phosphorothioate linkage at the site of ligation junction. The efficiency of 5′-phosphorothioate directed ligation reaction by ATP dependent DNA ligase reaction is similar to conventional 5′-phosphate ligation. The utility of enzymatic ligation in probing specific sequences of DNA is also described. The present invention also provides a novel non-enzymatic ligation of 5′-phosphorothioates that has been applied to the synthesis of single strand phosphorothioate and phosphate circular DNA.

Abstract: Disclosed are compositions and methods for amplification of RNA molecules. The disclosed method involves synthesizing first strand cDNA molecules from RNA molecules, circularizing the first strand cDNA molecules and replicating the circularized first strand cDNA molecules using rolling circle replication. The method can be aided by the use of specialized primers for cDNA synthesis and specialized probes for circularizing the first strand cDNA molecules. The method can be used to replicate and amplify multiple RNA molecules, such as all RNA molecules in a sample or all mRNA molecules in a sample, or be used to replicate and amplify specific RNA molecules. Rolling circle replication of the circularized first strand cDNA molecules results in long DNA strands containing tandem repeats of the cDNA sequence. The tandem sequence DNA can be used directly (for detection of sequences, for example), further amplified, or used any other purpose.

Abstract: Disclosed is a method and compositions for the sensitive detection of the amount and location of specific nucleic acid sequences. The method makes use of a branched oligomer, referred to as a lollipop oligomer, that has a tail portion, a right arm portion, and a left arm portion. These three components are joined at a common junction making a three-tailed structure. The two arms each end with sequences complementary to adjacent sequences in a target sequence. This allows the right and left arms to be ligated together when the oligomer is hybridized to the target sequence, thus topologically linking the oligomer to the target sequence. The tail portion can then be detected at the location of the target sequence.

Abstract: The present invention provides a novel method for ligation of oligonucleotides containing 5′-phosphorothioates on complementary templates by the action of DNA ligases. This reaction is readily applied to the synthesis of a single stranded circular DNA containing a phosphorothioate linkage at the site of ligation junction. The efficiency of 5′-phosphorothioate directed ligation reaction by ATP dependent DNA ligase reaction is similar to conventional 5′-phosphate ligation. The utility of enzymatic ligation in probing specific sequences of DNA is also described. The present invention also provides a novel non-enzymatic ligation of 5′-phosphorothioates that has been applied to the synthesis of single strand phosphorothioate and phosphate circular DNA.

Abstract: The present invention provides a novel method for ligation of oligonucleotides containing 5′-phosphorothioates on complementary templates by the action of DNA ligases. This reaction is readily applied to the synthesis of a single stranded circular DNA containing a phosphorothioate linkage at the site of ligation junction. The efficiency of 5′-phosphorothioate directed ligation reaction by ATP dependent DNA ligase reaction is similar to conventional 5′-phosphate ligation. The utility of enzymatic ligation in probing specific sequences of DNA is also described. The present invention also provides a novel non-enzymatic ligation of 5′-phosphorothioates that has been applied to the synthesis of single strand phosphorothioate and phosphate circular DNA.