Mahmoud Kandeel

Learn More
Plasmodium falciparum thymidylate kinase (PfTMK) is a promising antimalarial target due to its unique substrate specificity. Recently, we reported that 2',3'-dideoxycarbocyclic thymidine showed moderate inhibitory activity and reported the related structure-activity relationship for inhibitors against PfTMK. In this study, we have designed and synthesized(More)
Gentamicin (GS) is a potent antimicrobial exhibiting concentration dependent bacterial killing. A high dose ofgentamicin (10 mg kg(-1)) is required to reach sufficient concentrations in specific fluids as cerebrospinal fluid and to be effective on antibiotics resistant bacteria as well as treatment of acute and dangerous illness. Using a rat model, the(More)
Plasmodium deoxyguanylate pathways are an attractive area of investigation for future metabolic and drug discovery studies due to their unique substrate specificities. We investigated the energetic contribution to guanylate kinase substrate binding and the forces underlying ligand recognition. In the range from 20 to 35°C, the thermodynamic profiles(More)
Plasmodium falciparum thymidylate kinase (PfTMK) can tolerate a range of substrates, which distinguishes it from other thymidylate kinases. The enzyme not only phosphorylates TMP and dUMP but can also tolerate bulkier purines, namely, dGMP, GMP, and dIMP. In order to probe the flexibility of PfTMK in accommodating ligands of various sizes, we developed 6(More)
Here we highlight the unusual substrate specificity of Plasmodium falciparum thymidylate kinase (PfTMK) and the validity of the enzyme as a new drug target. Furthermore, we predict that the Anaplasma marginale enzyme has attractive domain constituents and may be functionally different from other TMPKs. We postulate that thymidylate kinases could have(More)
The new emerging Middle East Respiratory Syndrome Coronavirus (MERS CoV) encodes several resistance proteins against the innate immune response of the host, including interferon (IFN) resistance. Monitoring of the status of such proteins will be important to track viral pathogenicity. In this study, molecular dynamics approaches were used to investigate(More)
In Plasmodium falciparum, deoxyguanylate was found to be a substrate for several DNA metabolizing enzymes. Guanylate kinase utilizes dGMP with very low specificity, which is estimated to be the lowest among well-known prokaryotic and eukaryotic enzymes. Furthermore, thymidylate kinase, which is a pyrimidine specific enzyme, was found to phosphorylate dGMP(More)
The gene encoding for nucleoside diphosphate kinase from Plasmodium falciparum was obtained by polymerase chain reaction (PCR) and expressed in Escherichia coli. Tracking kinases is strenuous work due to many functional and technical deficits. Tracking of Plasmodium falciparum nucleoside diphosphate kinase (PfNDK) was carried out by conventional enzyme(More)
Nucleoside diphosphate kinases (NDKs) play a key role in maintaining the intracellular energy resources as well as the balance of nucleotide pools. Recently, attention has been directed to NDKs owing to its role in activating various chemotherapeutic agents. The binding affinity of different nucleotides with P. falciparum NDK was varied according to the(More)
RNA interference (RNAi) is a highly specialized process of protein-siRNA interaction that results in the regulation of gene expression and cleavage of target mRNA. The PAZ domain of the Argonaute proteins binds to the 3' end of siRNA, and during RNAi the attaching end of the siRNA switches between binding and release from its binding pocket. This biphasic(More)