The Woods Hole air/space oceanographic program for 1969 is discussed. Studies included: (1) monit... more The Woods Hole air/space oceanographic program for 1969 is discussed. Studies included: (1) monitoring the sharp temperature boundary of the Gulf Stream by microwave and infrared observation, (2) spectrophotometry of the Gulf Stream and the adjacent continental slope and shelf water over Georges Bank, (3) interpretation of cloud and other meteorological data in terms of the effects of wind and sun on the upper ocean, (4) a sea state test plan, (5) systems research, and (6) ocean data recovery by aircraft and satellite.
Juvenile hormone (JH) is vital to normal insect growth and development. In the lepidopteran speci... more Juvenile hormone (JH) is vital to normal insect growth and development. In the lepidopteran species of Manduca Sexta, JH consists of five different methyl epoxy-farnesoate homologs, which are produced via the terpenoid biosynthetic pathway. Prenyltransferase, which catalyzes the formation of the JH carbon backbone, is a key enzyme of this pathway since it may be partially responsible for control of JH homolog production. This research was concerned with the optimization and characterization of lepidopteran prenyltransferase activity in M. Sexta larval corpora allata. Substrate specificity studies were performed that involved the examination of all possible natural and unnatural methyl/ethyl coupling patterns of dimethylallyl diphosphate and geranyl diphosphate. This required the synthesis of all possible natural and unnatural methyl/ethyl homologs of dimethylallyl diphosphate and geranyl diphosphate, as well as those of farnesol. Optimum prenyltransferase activity was obtained with corpora allata homogenates containing 2% Triton X-100, 0.15% BSA, 25% glycerol (all w/v), 2.5 mM MgCl$\sb2$, 10 mM KF, and 0.5 mM mercaptoethanol. Detergents usually do not increase short-chained prenyltransferase activity; however, this system displayed significant enhancement of enzymatic activity in the presence of non-ionic detergents. M. Sexta prenyltransferase activity required divalent cations and had a broad pH maxima. Enzyme localization studies determined that the protein is cytosolic. K$\sb{\rm M}$ values of 6.2 and 3.0 $\mu$M were determined for GPP and IPP, respectively. Enzymatic activity was inhibited by phosphate, diphosphate, NEM, and GGPP. The homologs of geranyl diphosphate were constructed in a convergent manner, by olefination of the corresponding trisnoraldehydes, obtained from terminal oxidative cleavage of geraniol, higher-order vinyl cuprate conjugate addition to acrolein, or cuprate conjugate addition to ethyl 2-pentynoate. To serve as authentic standards, farnesol homologs were prepared by barium-stabilized allylic coupling of the geranyl derivatives to either C-5 or C-6 allylic bromides. Substrate specificity studies using the prepared DMAPP and GPP homologs found that lepidopteran prenyltransferase differs from other short-chain prenyltransferases since it readily accepts ethyl-containing homologs while other enzymes do not
DNA Surveillance is a Web-based application that assists in the identification of the species and... more DNA Surveillance is a Web-based application that assists in the identification of the species and population of unknown specimens by aligning user-submitted DNA sequences with a validated and curated data set of reference sequences. Phylogenetic analyses are performed and results are returned in tree and table format summarizing the evolutionary distances between the query and reference sequences. DNA Surveillance is implemented with mitochondrial DNA (mtDNA) control region sequences representing the majority of recognized cetacean species. Extensions of the system to include other gene loci and taxa are planned. The service, including instructions and sample data, is available at
In discrete event steady-state simulation, deletion the initial transient phase of the simulation... more In discrete event steady-state simulation, deletion the initial transient phase of the simulation is usually recommended in order to reduce. Various heuristics and tests have been proposed to aid with this. The plummeting cost of simulation, combined with uncertainties about the overall reliability of transient methods, suggest revisiting the notion that deletion is essential, especially for longer simulations. We consider this in a sequential simulation framework. The results show, that for run lengths giving commonly used relative precisions of the results, there is no substantial difference in point or interval estimates of means due to deleting the initial transient. However in sequential simulation, deleting the initial transient turns out to have considerable value in reducing the chance of premature stopping, thus ensuring that the accuracy of the final results is closer to that specified.
Monolayer physisorbed CO on NaCl(100) single crystal surfaces has been investigated with polarize... more Monolayer physisorbed CO on NaCl(100) single crystal surfaces has been investigated with polarized Fourier transform infrared (FTIR) spectroscopy at 5 K. While the fundamental (v = 1 ←v = 0) transition of the monolayer has been studied previously, we report for the first time the overtone (v = 2 ←v = 0) transition. Its integrated absorbance is very weak, being only 0.5% of the fundamental. Comparisons of the transition frequencies, the bandwidths and absorbances for these two transitions together with those of dilute isotopes allow us to isolate the contribution of dynamic and static coupling effects of molecules within the monolayer. We can also distinguish homogeneous and heterogeneous effects from band profiles of these various transitions. The method of analysis of these data is the exciton model appropriate to treating the coupling of the electric multipoles of molecules within the adlayer.
Yvonne Freer, Neil McIntosh, Lindsey Ferguson, Gary Ewing, Robert Logie, Jim Hunter, Sue Rudkin. ... more Yvonne Freer, Neil McIntosh, Lindsey Ferguson, Gary Ewing, Robert Logie, Jim Hunter, Sue Rudkin. Simpson Centre for Reproductive Health, Edinburgh. Background: In a complex environment such as the NICU, decision support aids need to take account of the optimal performance ability of decision-makers of varying types and levels of responsibility. Card sorting experiments were performed as part of the initial phase of a project, called NEONATE, with the aim to elicit these differences prior to developing decision support tools. They were performed using “patient descriptor” and “clinical action” words. Methods: 32 staff (8 each of senior and junior doctors and nurses) participated in the experiments. The cardsorts data were analysed using conventional cluster analysis to produce dendrograms. Results: The patterns that emerged were remarkably similar between the various groups of staff excepting junior doctors in “descriptor” sorts and junior nurses in “action” sorts. In the former there appeared to be little discernment in the elements of elimination, infant posture, tone and movement and sleep wake states. In the latter, junior nurses were unable to separate out the various components of assessment from delivery of care. More subtle differences in a group content were principally associated with refinement of a descriptor/action or perceived linkage between 2 or more features (table 1). Conclusions: The differences in practitioner experience as well as role and expected performance were demonstrated by these card sort experiments. How this affects infant outcome needs to be assessed and decision support aids developed accordingly.
Generation of 6-oxyl radicals from homoribofuranose (5-deoxy-D-ribo-hexofuranose) 6-O-nitro ester... more Generation of 6-oxyl radicals from homoribofuranose (5-deoxy-D-ribo-hexofuranose) 6-O-nitro esters with Bu3SnDIAIBNIbenzenelA resulted in abstraction of H3 by a [I,5]-hydrogen atom shift. Transfer of 2H from the stannane to eC3 effected incorporation of deuterium at C3. Analogous treatment of 6-azido-6-deoxy-D-ribohexofuranose derivatives gave C3-deuterated aminosugars. In contrast, no deuterium incorporation was detected upon parallel treatment of 6-thio-D-ribo-hexofuranose derivatives. Abstraction of H3' by a thiyl radical (oSCys) is the postulated first step in reactions that are utilized by ribonucleotide reductases to convert ribonucleotides into 2'-deoxynucleotides. Results are discussed relative to the enzyme reaction cascade that couples abstraction of H3' with irreversible loss of water from C2'.
Ion mobility spectrometry has become the most successful and widely used technology for the detec... more Ion mobility spectrometry has become the most successful and widely used technology for the detection of trace levels of nitro-organic explosives on handbags and carry on-luggage in airports throughout the US. The low detection limits are provided by the efficient ionization process, namely, atmospheric pressure chemical ionization (APCI) reactions in negative polarity. An additional level of confidence in a measurement is imparted by characterization of ions for mobilities in weak electric fields of a drift tube at ambient pressure. Findings from over 30 years of investigations into IMS response to these explosives have been collected and assessed to allow a comprehensive view of the APCI reactions characteristic of nitro-organic explosives. Also, the drift tube conditions needed to obtain particular mobility spectra have been summarized. During the past decade, improvements have occurred in IMS on the understanding of reagent gas chemistries, the influence of temperature on ion stability, and sampling methods. In addition, commercial instruments have been refined to provide fast and reliable measurements for on-site detection of explosives. The gas phase ion chemistry of most explosives is mediated by the fragile C ONO 2 bonds or the acidity of protons. Thus, M − or M•Cl − species are found with only a few explosives and loss of NO 2 , NO 3 and proton abstraction reactions are common and complicating pathways. However, once ions are formed, they appear to have stabilities on time scales equal to or longer than ion drift times from 5-20 ms. As such, peak shapes in IMS are suitable for high selectivity and sensitivity.
Treatment of 1,2-O-isopropylidenefuranose derivatives with triethylsilane/boron trifluoride ether... more Treatment of 1,2-O-isopropylidenefuranose derivatives with triethylsilane/boron trifluoride etherate results in generation of the corresponding tetrahydrofurans. This one-stage process removes the 1,2-O-isopropylidene group with accompanying deoxygenation at the anomeric position and is compatible with several hydroxyl protecting groups.
We have obtained the first conclusiVe chemical evidence consistent with the controversial first t... more We have obtained the first conclusiVe chemical evidence consistent with the controversial first two steps in the mechanism postulated to occur during reductive deoxygenation at the active site of ribonucleotide reductases. 2,3 Generation of a proximal primary aliphatic thiyl radical in a tetrahydrofuran model substituted at C2 with a radical leaving group results in abstraction of H3 and elimination of phenylsulfinyl from C2. Ribonucleotide reductases catalyze the deoxygenative reduction of ribonucleoside 5′-(di or tri)phosphates to 2′-deoxynucleotides and provide the only de novo source of DNA components. The ribonucleoside 5′-diphosphate reductase (RDPR) from Escherichia coli has been studied extensively. 4 Its R1 homodimer subunit contains substrate and allosteric binding sites and cysteine residues required for catalysis. The R2 homodimer contains a diiron chelate and an essential tyrosyl free radical. 2-5 Mammalian and certain viral-encoded RDPRs are similar. A postulated radical-cascade mechanism for substrate reduction invokes long-range electron transfer between •OTyr122 (in R2) and Cys439 (in R1) at the active site interface. The •SCys439 radical generated in proximity with the face of the substrate is proposed 2,3 to abstract the 3′hydrogen atom as the first substrate-activation step (Scheme 1 3). Abstraction of H3′ from 1 by a primary aliphatic thiyl radical to generate 2 has aroused debate, 2e owing to the absence of an appropriate chemical precedent. We have shown that aminyl or oxyl radicals at C6 of hexofuranosyl models abstract H3 by a [1,5]-hydrogen shift. 1,6 Treatment (Bu 3 SnD/AIBN/benzene/∆) of 6-azido or 6-O-nitro precursors produces C3 radicals that undergo deuterium transfer from the stannane to give 3-[ 2 H] product(s). The absence of (H f D) exchange at C3 with a 6-S• radical in models that operate with 6-O• (60-80%) or 6-N• (∼20%) radicals was troubling. 1 However, RDPR executes abstraction of H3′ and a [1,2]-electron shift coupled with hydrogen transfer from O3′ to O2′ and "irreversible" loss of water from C2′ to give the stabilized oxallyl radical 3 (Scheme 1). 3 We now have synthesized thioether 5 (and control nitrate ester 11) with a phenylsulfinyl radical leaving group 7 at C2 to more closely model the enzyme process.
ABSTRACT The biosynthesis of insect juvenile hormone (JH) is due, in part, to the precise head-to... more ABSTRACT The biosynthesis of insect juvenile hormone (JH) is due, in part, to the precise head-to-tail coupling of allylic and homoallylic diphosphate substrates, as catalyzed by one or more prenyltransferases. To better understand this enzyme's role in JH production, homodimethylallyl diphosphate and both the natural and unnatural homologs of geranyl diphosphate have been prepared as potential substrates for insect prenyltransferase. These latter materials were constructed in a convergent manner by olefination of the corresponding trisnoraldehydes obtained from either terminal oxidative cleavage of geraniol or higher-order cuprate conjugate addition to acrolein. To aid in characterizing the nature of the terpenoid skeletons formed from our in vitro studies, homologous derivatives of farnesol were also prepared by anion coupling of the geranyl derivatives to either C5 or C6 allylic bromides. The preparation of these materials and the results of incubations with larval corpora allata homogenates of the lepidopteran Manduca sexta are described.
Treatment of homoadenosine [9-(5-deoxy-beta-D-ribo-hexofuranosyl)adenine] with thionyl chloride a... more Treatment of homoadenosine [9-(5-deoxy-beta-D-ribo-hexofuranosyl)adenine] with thionyl chloride and pyridine in acetonitrile gave 6'-chloro-6'-deoxyhomoadenosine, which underwent nucleophilic displacement with L-cysteine or L-homocysteine to give homologated analogues of S-adenosyl-L-homocysteine. Each amino acid in aqueous sodium hydroxide at 60 degrees C gave excellent conversion from the chloronucleoside, and adsorption on Amberlite XAD-4 resin provided more convenient isolation than prior methods. Weak binding of these non-hydrolyzed analogues to S-adenosyl-L-homocysteine hydrolase was observed.
The prenyl transferase, farnesyl pyrophosphate (FPP) synthase, which catalyzes the head-to-tail c... more The prenyl transferase, farnesyl pyrophosphate (FPP) synthase, which catalyzes the head-to-tail couplings of dimethylallyl pyrophosphate (DMAPP) and geranyl pyrophosphate (GPP) with isopentenyl pyrophosphate (IPP), is a key enzyme in juvenile hormone (JH) ...
The Woods Hole air/space oceanographic program for 1969 is discussed. Studies included: (1) monit... more The Woods Hole air/space oceanographic program for 1969 is discussed. Studies included: (1) monitoring the sharp temperature boundary of the Gulf Stream by microwave and infrared observation, (2) spectrophotometry of the Gulf Stream and the adjacent continental slope and shelf water over Georges Bank, (3) interpretation of cloud and other meteorological data in terms of the effects of wind and sun on the upper ocean, (4) a sea state test plan, (5) systems research, and (6) ocean data recovery by aircraft and satellite.
Juvenile hormone (JH) is vital to normal insect growth and development. In the lepidopteran speci... more Juvenile hormone (JH) is vital to normal insect growth and development. In the lepidopteran species of Manduca Sexta, JH consists of five different methyl epoxy-farnesoate homologs, which are produced via the terpenoid biosynthetic pathway. Prenyltransferase, which catalyzes the formation of the JH carbon backbone, is a key enzyme of this pathway since it may be partially responsible for control of JH homolog production. This research was concerned with the optimization and characterization of lepidopteran prenyltransferase activity in M. Sexta larval corpora allata. Substrate specificity studies were performed that involved the examination of all possible natural and unnatural methyl/ethyl coupling patterns of dimethylallyl diphosphate and geranyl diphosphate. This required the synthesis of all possible natural and unnatural methyl/ethyl homologs of dimethylallyl diphosphate and geranyl diphosphate, as well as those of farnesol. Optimum prenyltransferase activity was obtained with corpora allata homogenates containing 2% Triton X-100, 0.15% BSA, 25% glycerol (all w/v), 2.5 mM MgCl$\sb2$, 10 mM KF, and 0.5 mM mercaptoethanol. Detergents usually do not increase short-chained prenyltransferase activity; however, this system displayed significant enhancement of enzymatic activity in the presence of non-ionic detergents. M. Sexta prenyltransferase activity required divalent cations and had a broad pH maxima. Enzyme localization studies determined that the protein is cytosolic. K$\sb{\rm M}$ values of 6.2 and 3.0 $\mu$M were determined for GPP and IPP, respectively. Enzymatic activity was inhibited by phosphate, diphosphate, NEM, and GGPP. The homologs of geranyl diphosphate were constructed in a convergent manner, by olefination of the corresponding trisnoraldehydes, obtained from terminal oxidative cleavage of geraniol, higher-order vinyl cuprate conjugate addition to acrolein, or cuprate conjugate addition to ethyl 2-pentynoate. To serve as authentic standards, farnesol homologs were prepared by barium-stabilized allylic coupling of the geranyl derivatives to either C-5 or C-6 allylic bromides. Substrate specificity studies using the prepared DMAPP and GPP homologs found that lepidopteran prenyltransferase differs from other short-chain prenyltransferases since it readily accepts ethyl-containing homologs while other enzymes do not
DNA Surveillance is a Web-based application that assists in the identification of the species and... more DNA Surveillance is a Web-based application that assists in the identification of the species and population of unknown specimens by aligning user-submitted DNA sequences with a validated and curated data set of reference sequences. Phylogenetic analyses are performed and results are returned in tree and table format summarizing the evolutionary distances between the query and reference sequences. DNA Surveillance is implemented with mitochondrial DNA (mtDNA) control region sequences representing the majority of recognized cetacean species. Extensions of the system to include other gene loci and taxa are planned. The service, including instructions and sample data, is available at
In discrete event steady-state simulation, deletion the initial transient phase of the simulation... more In discrete event steady-state simulation, deletion the initial transient phase of the simulation is usually recommended in order to reduce. Various heuristics and tests have been proposed to aid with this. The plummeting cost of simulation, combined with uncertainties about the overall reliability of transient methods, suggest revisiting the notion that deletion is essential, especially for longer simulations. We consider this in a sequential simulation framework. The results show, that for run lengths giving commonly used relative precisions of the results, there is no substantial difference in point or interval estimates of means due to deleting the initial transient. However in sequential simulation, deleting the initial transient turns out to have considerable value in reducing the chance of premature stopping, thus ensuring that the accuracy of the final results is closer to that specified.
Monolayer physisorbed CO on NaCl(100) single crystal surfaces has been investigated with polarize... more Monolayer physisorbed CO on NaCl(100) single crystal surfaces has been investigated with polarized Fourier transform infrared (FTIR) spectroscopy at 5 K. While the fundamental (v = 1 ←v = 0) transition of the monolayer has been studied previously, we report for the first time the overtone (v = 2 ←v = 0) transition. Its integrated absorbance is very weak, being only 0.5% of the fundamental. Comparisons of the transition frequencies, the bandwidths and absorbances for these two transitions together with those of dilute isotopes allow us to isolate the contribution of dynamic and static coupling effects of molecules within the monolayer. We can also distinguish homogeneous and heterogeneous effects from band profiles of these various transitions. The method of analysis of these data is the exciton model appropriate to treating the coupling of the electric multipoles of molecules within the adlayer.
Yvonne Freer, Neil McIntosh, Lindsey Ferguson, Gary Ewing, Robert Logie, Jim Hunter, Sue Rudkin. ... more Yvonne Freer, Neil McIntosh, Lindsey Ferguson, Gary Ewing, Robert Logie, Jim Hunter, Sue Rudkin. Simpson Centre for Reproductive Health, Edinburgh. Background: In a complex environment such as the NICU, decision support aids need to take account of the optimal performance ability of decision-makers of varying types and levels of responsibility. Card sorting experiments were performed as part of the initial phase of a project, called NEONATE, with the aim to elicit these differences prior to developing decision support tools. They were performed using “patient descriptor” and “clinical action” words. Methods: 32 staff (8 each of senior and junior doctors and nurses) participated in the experiments. The cardsorts data were analysed using conventional cluster analysis to produce dendrograms. Results: The patterns that emerged were remarkably similar between the various groups of staff excepting junior doctors in “descriptor” sorts and junior nurses in “action” sorts. In the former there appeared to be little discernment in the elements of elimination, infant posture, tone and movement and sleep wake states. In the latter, junior nurses were unable to separate out the various components of assessment from delivery of care. More subtle differences in a group content were principally associated with refinement of a descriptor/action or perceived linkage between 2 or more features (table 1). Conclusions: The differences in practitioner experience as well as role and expected performance were demonstrated by these card sort experiments. How this affects infant outcome needs to be assessed and decision support aids developed accordingly.
Generation of 6-oxyl radicals from homoribofuranose (5-deoxy-D-ribo-hexofuranose) 6-O-nitro ester... more Generation of 6-oxyl radicals from homoribofuranose (5-deoxy-D-ribo-hexofuranose) 6-O-nitro esters with Bu3SnDIAIBNIbenzenelA resulted in abstraction of H3 by a [I,5]-hydrogen atom shift. Transfer of 2H from the stannane to eC3 effected incorporation of deuterium at C3. Analogous treatment of 6-azido-6-deoxy-D-ribohexofuranose derivatives gave C3-deuterated aminosugars. In contrast, no deuterium incorporation was detected upon parallel treatment of 6-thio-D-ribo-hexofuranose derivatives. Abstraction of H3' by a thiyl radical (oSCys) is the postulated first step in reactions that are utilized by ribonucleotide reductases to convert ribonucleotides into 2'-deoxynucleotides. Results are discussed relative to the enzyme reaction cascade that couples abstraction of H3' with irreversible loss of water from C2'.
Ion mobility spectrometry has become the most successful and widely used technology for the detec... more Ion mobility spectrometry has become the most successful and widely used technology for the detection of trace levels of nitro-organic explosives on handbags and carry on-luggage in airports throughout the US. The low detection limits are provided by the efficient ionization process, namely, atmospheric pressure chemical ionization (APCI) reactions in negative polarity. An additional level of confidence in a measurement is imparted by characterization of ions for mobilities in weak electric fields of a drift tube at ambient pressure. Findings from over 30 years of investigations into IMS response to these explosives have been collected and assessed to allow a comprehensive view of the APCI reactions characteristic of nitro-organic explosives. Also, the drift tube conditions needed to obtain particular mobility spectra have been summarized. During the past decade, improvements have occurred in IMS on the understanding of reagent gas chemistries, the influence of temperature on ion stability, and sampling methods. In addition, commercial instruments have been refined to provide fast and reliable measurements for on-site detection of explosives. The gas phase ion chemistry of most explosives is mediated by the fragile C ONO 2 bonds or the acidity of protons. Thus, M − or M•Cl − species are found with only a few explosives and loss of NO 2 , NO 3 and proton abstraction reactions are common and complicating pathways. However, once ions are formed, they appear to have stabilities on time scales equal to or longer than ion drift times from 5-20 ms. As such, peak shapes in IMS are suitable for high selectivity and sensitivity.
Treatment of 1,2-O-isopropylidenefuranose derivatives with triethylsilane/boron trifluoride ether... more Treatment of 1,2-O-isopropylidenefuranose derivatives with triethylsilane/boron trifluoride etherate results in generation of the corresponding tetrahydrofurans. This one-stage process removes the 1,2-O-isopropylidene group with accompanying deoxygenation at the anomeric position and is compatible with several hydroxyl protecting groups.
We have obtained the first conclusiVe chemical evidence consistent with the controversial first t... more We have obtained the first conclusiVe chemical evidence consistent with the controversial first two steps in the mechanism postulated to occur during reductive deoxygenation at the active site of ribonucleotide reductases. 2,3 Generation of a proximal primary aliphatic thiyl radical in a tetrahydrofuran model substituted at C2 with a radical leaving group results in abstraction of H3 and elimination of phenylsulfinyl from C2. Ribonucleotide reductases catalyze the deoxygenative reduction of ribonucleoside 5′-(di or tri)phosphates to 2′-deoxynucleotides and provide the only de novo source of DNA components. The ribonucleoside 5′-diphosphate reductase (RDPR) from Escherichia coli has been studied extensively. 4 Its R1 homodimer subunit contains substrate and allosteric binding sites and cysteine residues required for catalysis. The R2 homodimer contains a diiron chelate and an essential tyrosyl free radical. 2-5 Mammalian and certain viral-encoded RDPRs are similar. A postulated radical-cascade mechanism for substrate reduction invokes long-range electron transfer between •OTyr122 (in R2) and Cys439 (in R1) at the active site interface. The •SCys439 radical generated in proximity with the face of the substrate is proposed 2,3 to abstract the 3′hydrogen atom as the first substrate-activation step (Scheme 1 3). Abstraction of H3′ from 1 by a primary aliphatic thiyl radical to generate 2 has aroused debate, 2e owing to the absence of an appropriate chemical precedent. We have shown that aminyl or oxyl radicals at C6 of hexofuranosyl models abstract H3 by a [1,5]-hydrogen shift. 1,6 Treatment (Bu 3 SnD/AIBN/benzene/∆) of 6-azido or 6-O-nitro precursors produces C3 radicals that undergo deuterium transfer from the stannane to give 3-[ 2 H] product(s). The absence of (H f D) exchange at C3 with a 6-S• radical in models that operate with 6-O• (60-80%) or 6-N• (∼20%) radicals was troubling. 1 However, RDPR executes abstraction of H3′ and a [1,2]-electron shift coupled with hydrogen transfer from O3′ to O2′ and "irreversible" loss of water from C2′ to give the stabilized oxallyl radical 3 (Scheme 1). 3 We now have synthesized thioether 5 (and control nitrate ester 11) with a phenylsulfinyl radical leaving group 7 at C2 to more closely model the enzyme process.
ABSTRACT The biosynthesis of insect juvenile hormone (JH) is due, in part, to the precise head-to... more ABSTRACT The biosynthesis of insect juvenile hormone (JH) is due, in part, to the precise head-to-tail coupling of allylic and homoallylic diphosphate substrates, as catalyzed by one or more prenyltransferases. To better understand this enzyme's role in JH production, homodimethylallyl diphosphate and both the natural and unnatural homologs of geranyl diphosphate have been prepared as potential substrates for insect prenyltransferase. These latter materials were constructed in a convergent manner by olefination of the corresponding trisnoraldehydes obtained from either terminal oxidative cleavage of geraniol or higher-order cuprate conjugate addition to acrolein. To aid in characterizing the nature of the terpenoid skeletons formed from our in vitro studies, homologous derivatives of farnesol were also prepared by anion coupling of the geranyl derivatives to either C5 or C6 allylic bromides. The preparation of these materials and the results of incubations with larval corpora allata homogenates of the lepidopteran Manduca sexta are described.
Treatment of homoadenosine [9-(5-deoxy-beta-D-ribo-hexofuranosyl)adenine] with thionyl chloride a... more Treatment of homoadenosine [9-(5-deoxy-beta-D-ribo-hexofuranosyl)adenine] with thionyl chloride and pyridine in acetonitrile gave 6'-chloro-6'-deoxyhomoadenosine, which underwent nucleophilic displacement with L-cysteine or L-homocysteine to give homologated analogues of S-adenosyl-L-homocysteine. Each amino acid in aqueous sodium hydroxide at 60 degrees C gave excellent conversion from the chloronucleoside, and adsorption on Amberlite XAD-4 resin provided more convenient isolation than prior methods. Weak binding of these non-hydrolyzed analogues to S-adenosyl-L-homocysteine hydrolase was observed.
The prenyl transferase, farnesyl pyrophosphate (FPP) synthase, which catalyzes the head-to-tail c... more The prenyl transferase, farnesyl pyrophosphate (FPP) synthase, which catalyzes the head-to-tail couplings of dimethylallyl pyrophosphate (DMAPP) and geranyl pyrophosphate (GPP) with isopentenyl pyrophosphate (IPP), is a key enzyme in juvenile hormone (JH) ...
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Papers by Gregory Ewing