alisa xhambazi - Academia.edu (original) (raw)
Papers by alisa xhambazi
Insect biochemistry and molecular biology, Jan 11, 2015
Farnesyl diphosphate synthase (FPPS) catalyzes the condensation of the non-allylic diphosphate, i... more Farnesyl diphosphate synthase (FPPS) catalyzes the condensation of the non-allylic diphosphate, isopentenyl diphosphate (IPP; C5), with the allylic diphosphate primer dimethylallyl diphosphate (DMAPP; C5) to generate the C15 prenyl chain (FPP) used for protein prenylation as well as sterol and terpene biosynthesis. Here, we designed and prepared a series of pyridinium bisphosphonate (PyrBP) compounds, with the aim of selectively inhibiting FPPS of the lepidopteran insect order. FPPSs of Drosophila melanogaster and the spruce budworm, Choristoneura fumiferana, were inhibited by several PyrBPs, and as hypothesized, larger bisphosphonates were more selective for the lepidopteran protein and completely inactive towards dipteran and vertebrate FPPSs. Cell growth of a D. melanogaster cell line was adversely affected by exposure to PyrPBs that were strongly inhibitory to insect FPPS, although their effect was less pronounced than that observed upon exposure to the electron transport disrup...
Insect Biochemistry and Molecular Biology, Aug 1, 2015
Farnesyl diphosphate synthase (FPPS) catalyzes the condensation of the non-allylic diphosphate, i... more Farnesyl diphosphate synthase (FPPS) catalyzes the condensation of the non-allylic diphosphate, isopentenyl diphosphate (IPP; C5), with the allylic diphosphate primer dimethylallyl diphosphate (DMAPP; C5) to generate the C15 prenyl chain (FPP) used for protein prenylation as well as sterol and terpene biosynthesis. Here, we designed and prepared a series of pyridinium bisphosphonate (PyrBP) compounds, with the aim of selectively inhibiting FPPS of the lepidopteran insect order. FPPSs of Drosophila melanogaster and the spruce budworm, Choristoneura fumiferana, were inhibited by several PyrBPs, and as hypothesized, larger bisphosphonates were more selective for the lepidopteran protein and completely inactive towards dipteran and vertebrate FPPSs. Cell growth of a D. melanogaster cell line was adversely affected by exposure to PyrPBs that were strongly inhibitory to insect FPPS, although their effect was less pronounced than that observed upon exposure to the electron transport disrupter, chlorfenapyr. To assess the impact of PyrBPs on lepidopteran insect growth and development, we performed feeding and topical studies, using the tobacco hornworm, Manduca sexta, as our insect model. The free acid form of a PyrBP and a known bisphosphonate inhibitor of vertebrate FPPS, alendronate, had little to no effect on larval M. sexta; however, the topical application of more lipophilic ester PyrBPs caused decreased growth, incomplete larval molting, cuticle darkening at the site of application, and for those insects that survived, the formation of larval-pupal hybrids. To gain a better understanding of the structural differences that produce selective lepidopteran FPPS inhibition, homology models of C. fumiferana and D. melanogaster FPPS (CfFPPS2, and DmFPPS) were prepared. Docking of substrates and PyrBPs demonstrates that differences at the -3 and -4 positions relative to the first aspartate rich motif (FARM) are important factors in the ability of the lepidopteran enzyme to produce homologous isoprenoid structure and to be selectively inhibited by larger PyrBPs.
Exploitation of photochemistry has allowed scientists to develop and construct three types of mol... more Exploitation of photochemistry has allowed scientists to develop and construct three types of molecular-level motors, namely catenane rotary motors, molecular walkers, and supramolecular pumps, all of which are capable of unidirectional movement and can potentially be used in application as molecular devices for responsive materials and surfaces, information storage, processing, drug delivery, etc .
Farnesyl diphosphate synthase (FPPS) catalyzes the condensation of the non-allylic diphosphate, i... more Farnesyl diphosphate synthase (FPPS) catalyzes the condensation of the non-allylic diphosphate, iso- pentenyl diphosphate (IPP; C5), with the allylic diphosphate primer dimethylallyl diphosphate (DMAPP; C5) to generate the C15 prenyl chain (FPP) used for protein prenylation as well as sterol and terpene biosynthesis. Here, we designed and prepared a series of pyridinium bisphosphonate (PyrBP) com- pounds, with the aim of selectively inhibiting FPPS of the lepidopteran insect order. FPPSs of Drosophila melanogaster and the spruce budworm, Choristoneura fumiferana, were inhibited by several PyrBPs, and as hypothesized, larger bisphosphonates were more selective for the lepidopteran protein and completely inactive towards dipteran and vertebrate FPPSs. Cell growth of a D. melanogaster cell line was adversely affected by exposure to PyrPBs that were strongly inhibitory to insect FPPS, although their effect was less pronounced than that observed upon exposure to the electron transport di...
Insect Biochemistry and Molecular Biology, 2015
Farnesyl diphosphate synthase (FPPS) catalyzes the condensation of the non-allylic diphosphate, i... more Farnesyl diphosphate synthase (FPPS) catalyzes the condensation of the non-allylic diphosphate, isopentenyl diphosphate (IPP; C5), with the allylic diphosphate primer dimethylallyl diphosphate (DMAPP; C5) to generate the C15 prenyl chain (FPP) used for protein prenylation as well as sterol and terpene biosynthesis. Here, we designed and prepared a series of pyridinium bisphosphonate (PyrBP) compounds, with the aim of selectively inhibiting FPPS of the lepidopteran insect order. FPPSs of Drosophila melanogaster and the spruce budworm, Choristoneura fumiferana, were inhibited by several PyrBPs, and as hypothesized, larger bisphosphonates were more selective for the lepidopteran protein and completely inactive towards dipteran and vertebrate FPPSs. Cell growth of a D. melanogaster cell line was adversely affected by exposure to PyrPBs that were strongly inhibitory to insect FPPS, although their effect was less pronounced than that observed upon exposure to the electron transport disrup...
Biological motion is a fundamental and very obvious attribute of all living organisms. In a cell,... more Biological motion is a fundamental and very obvious attribute of all living organisms. In a cell, molecular motor proteins are able to perform a myriad of complex functions that make life possible, for example walking along a cytoskeletal track to transport a variety of different types of cargos. Mimicking such sophisticated and complex molecule-based motors from a design and synthesis perspective is certainly a daunting task. However, many scientists have risen to the challenge in the last few decades and have created simple prototypes of molecular machines that are able to move in a processive, unidirectional, and controlled manner. As with biological motors that convert chemical energy into movement, the three motor types described here have been developed to exploit light energy as the fuel source to drive movement. In this context I describe the latest development of rotary catenanes, molecular walkers, and supramolecular pumps.
Insect biochemistry and molecular biology, Jan 11, 2015
Farnesyl diphosphate synthase (FPPS) catalyzes the condensation of the non-allylic diphosphate, i... more Farnesyl diphosphate synthase (FPPS) catalyzes the condensation of the non-allylic diphosphate, isopentenyl diphosphate (IPP; C5), with the allylic diphosphate primer dimethylallyl diphosphate (DMAPP; C5) to generate the C15 prenyl chain (FPP) used for protein prenylation as well as sterol and terpene biosynthesis. Here, we designed and prepared a series of pyridinium bisphosphonate (PyrBP) compounds, with the aim of selectively inhibiting FPPS of the lepidopteran insect order. FPPSs of Drosophila melanogaster and the spruce budworm, Choristoneura fumiferana, were inhibited by several PyrBPs, and as hypothesized, larger bisphosphonates were more selective for the lepidopteran protein and completely inactive towards dipteran and vertebrate FPPSs. Cell growth of a D. melanogaster cell line was adversely affected by exposure to PyrPBs that were strongly inhibitory to insect FPPS, although their effect was less pronounced than that observed upon exposure to the electron transport disrup...
Insect Biochemistry and Molecular Biology, Aug 1, 2015
Farnesyl diphosphate synthase (FPPS) catalyzes the condensation of the non-allylic diphosphate, i... more Farnesyl diphosphate synthase (FPPS) catalyzes the condensation of the non-allylic diphosphate, isopentenyl diphosphate (IPP; C5), with the allylic diphosphate primer dimethylallyl diphosphate (DMAPP; C5) to generate the C15 prenyl chain (FPP) used for protein prenylation as well as sterol and terpene biosynthesis. Here, we designed and prepared a series of pyridinium bisphosphonate (PyrBP) compounds, with the aim of selectively inhibiting FPPS of the lepidopteran insect order. FPPSs of Drosophila melanogaster and the spruce budworm, Choristoneura fumiferana, were inhibited by several PyrBPs, and as hypothesized, larger bisphosphonates were more selective for the lepidopteran protein and completely inactive towards dipteran and vertebrate FPPSs. Cell growth of a D. melanogaster cell line was adversely affected by exposure to PyrPBs that were strongly inhibitory to insect FPPS, although their effect was less pronounced than that observed upon exposure to the electron transport disrupter, chlorfenapyr. To assess the impact of PyrBPs on lepidopteran insect growth and development, we performed feeding and topical studies, using the tobacco hornworm, Manduca sexta, as our insect model. The free acid form of a PyrBP and a known bisphosphonate inhibitor of vertebrate FPPS, alendronate, had little to no effect on larval M. sexta; however, the topical application of more lipophilic ester PyrBPs caused decreased growth, incomplete larval molting, cuticle darkening at the site of application, and for those insects that survived, the formation of larval-pupal hybrids. To gain a better understanding of the structural differences that produce selective lepidopteran FPPS inhibition, homology models of C. fumiferana and D. melanogaster FPPS (CfFPPS2, and DmFPPS) were prepared. Docking of substrates and PyrBPs demonstrates that differences at the -3 and -4 positions relative to the first aspartate rich motif (FARM) are important factors in the ability of the lepidopteran enzyme to produce homologous isoprenoid structure and to be selectively inhibited by larger PyrBPs.
Exploitation of photochemistry has allowed scientists to develop and construct three types of mol... more Exploitation of photochemistry has allowed scientists to develop and construct three types of molecular-level motors, namely catenane rotary motors, molecular walkers, and supramolecular pumps, all of which are capable of unidirectional movement and can potentially be used in application as molecular devices for responsive materials and surfaces, information storage, processing, drug delivery, etc .
Farnesyl diphosphate synthase (FPPS) catalyzes the condensation of the non-allylic diphosphate, i... more Farnesyl diphosphate synthase (FPPS) catalyzes the condensation of the non-allylic diphosphate, iso- pentenyl diphosphate (IPP; C5), with the allylic diphosphate primer dimethylallyl diphosphate (DMAPP; C5) to generate the C15 prenyl chain (FPP) used for protein prenylation as well as sterol and terpene biosynthesis. Here, we designed and prepared a series of pyridinium bisphosphonate (PyrBP) com- pounds, with the aim of selectively inhibiting FPPS of the lepidopteran insect order. FPPSs of Drosophila melanogaster and the spruce budworm, Choristoneura fumiferana, were inhibited by several PyrBPs, and as hypothesized, larger bisphosphonates were more selective for the lepidopteran protein and completely inactive towards dipteran and vertebrate FPPSs. Cell growth of a D. melanogaster cell line was adversely affected by exposure to PyrPBs that were strongly inhibitory to insect FPPS, although their effect was less pronounced than that observed upon exposure to the electron transport di...
Insect Biochemistry and Molecular Biology, 2015
Farnesyl diphosphate synthase (FPPS) catalyzes the condensation of the non-allylic diphosphate, i... more Farnesyl diphosphate synthase (FPPS) catalyzes the condensation of the non-allylic diphosphate, isopentenyl diphosphate (IPP; C5), with the allylic diphosphate primer dimethylallyl diphosphate (DMAPP; C5) to generate the C15 prenyl chain (FPP) used for protein prenylation as well as sterol and terpene biosynthesis. Here, we designed and prepared a series of pyridinium bisphosphonate (PyrBP) compounds, with the aim of selectively inhibiting FPPS of the lepidopteran insect order. FPPSs of Drosophila melanogaster and the spruce budworm, Choristoneura fumiferana, were inhibited by several PyrBPs, and as hypothesized, larger bisphosphonates were more selective for the lepidopteran protein and completely inactive towards dipteran and vertebrate FPPSs. Cell growth of a D. melanogaster cell line was adversely affected by exposure to PyrPBs that were strongly inhibitory to insect FPPS, although their effect was less pronounced than that observed upon exposure to the electron transport disrup...
Biological motion is a fundamental and very obvious attribute of all living organisms. In a cell,... more Biological motion is a fundamental and very obvious attribute of all living organisms. In a cell, molecular motor proteins are able to perform a myriad of complex functions that make life possible, for example walking along a cytoskeletal track to transport a variety of different types of cargos. Mimicking such sophisticated and complex molecule-based motors from a design and synthesis perspective is certainly a daunting task. However, many scientists have risen to the challenge in the last few decades and have created simple prototypes of molecular machines that are able to move in a processive, unidirectional, and controlled manner. As with biological motors that convert chemical energy into movement, the three motor types described here have been developed to exploit light energy as the fuel source to drive movement. In this context I describe the latest development of rotary catenanes, molecular walkers, and supramolecular pumps.