Mahmoud Kandeel

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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)
The present work describes cloning, expression, purification, characterization, and mutation of Plasmodium falciparum guanylate kinase (PlasmoDB ID PFI1420w). Amino-acid sequence alignment revealed important differences especially in K42-V51, Y73-A77, and F100-L110, which include residues important for kinase activity, and at helix 3, which is important for(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)
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)
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)
To elucidate the role of the sugar moiety in the two natural nucleotides of the 3'-overhang region of small interfering RNA (siRNA), we synthesized siRNAs that incorporated two abasic nucleosides, 1-deoxy-D-ribofuranose (R(H)). We improved the method for preparing an O-protected abasic nucleoside, 1-deoxy-2,3,5-tri-O-benzoyl-β-D-ribofuranose, via the(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)
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 critical cellular pathway activated by double stranded RNA and regulates the gene expression of target mRNA. During RNAi, the 3' end of siRNA binds with the PAZ domain, followed by release and rebinding in a cyclic manner, which deemed essential for proper gene silencing. Recently, we provided the forces underlying the(More)
Plasmodium falciparum thymidylate kinase (PfTMK) is a potential chemotherapeutic target as it can tolerate a range of substrates, which distinguishes it from other thymidylate kinases. An important step in drug development is to determine the interaction of ligands competing for their target sites in a proposed drug target. The estimated binding affinity of(More)