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RESEARCH
Building Blocks Synthesized Chemists can n o w make simple f r a g ments o f nucleic acids V ^ H E M I S T S h a v e passed three m o r e milestones marking the p a t h toward eiiemical u n d e r s t a n d i n g of t h e nucleie a c i d s . Researchers a t British Columbia Research Council (Vancouver, B. C.) c a n now synthesize polymers ( u p t o 1 1 units) of simple nucleotides, separ a t e them into p u r e fractions, a n d d e g r a d e them from either e n d b y choice o f enzyme. These successes» though, still leave chemists a long way from t h e s e goals: • Knowing in w h a t order nucleotides o c c u r in n a t u r a l nucleic acid. • H o w t o build a replica of a n a t „.~11~. ~. _ ,
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But this new work points t h e w a y t o w a r d doing just tiiose things. A n d , b y providing a w a y of m a k i n g polynucleotides of k n o w n composition a n d c h a i n length, it also is a w a y to study t h e action of enzymes in nucleotide metabolism. Scientists k n o w already that nucleie acids D N A a n d RINFA are concerned intimately with life—that RNA is inv o l v e d in p r o t e i n synthesis, D N A with t h e transfer of hereditary characteristics. While some groups study these biological e v e n t s a n d others seek t o unravel t h e physical and chemical structures of D N A and R N A , a team o f chemists in British Columbia, headed l>y H . G. Khorana, plans to get at t h e problem b y making Icnown polynucleotides, finding enzymes with specificactivities for specific nucleotide bonds, a n d then applying this knowledge t o n a t u r a l nucleic a c i d s . • M a k i n g Polynucleotides. Khora n a , G. M . T e n e r , a n d coworkers start directly with unprotected mononucleot i d e s ; for example, thymidine-5' phos-
phate. T h e y then activate this w i t h dicyclohexylcarbodiimide ( D C C ) in pyridine at room t e m p e r a t u r e . T h e y get a Oxike's mixture of polymers, in-
cluding t h e dinueleotide, the trinucleotide, and longer members of this series up to 11 units. And, b e c a u s e these polymers h a v e reactive radicals a t each SEPT.
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end, tlicy also get a corresponding cyclic series up to a chain length of five. After that the two ends are too far apart to cyelize. Ρ Separating Them. They isolate these pohiners by passing them tlirougii a chromatographic column of diethylaminoethyl cellulose o r similar alkylarriino-substituted celluloses. So far, tlvey have isolated and character· ized tlie 2, 3 , 4, and 5-membered poly mers, both linear and cyclic. They have e-luted! higher members of the series from the cellulose columns but ' have mot yet investigated them. • Making; Mixed Polynucleotides» They tiave also adapted these methods to make di- and trinucleotides having different purine and pyridine bases o n the ribose structure. The secret is t o block t h e phosphate group on the nucleoside containing one base and the hyclroxyl group on the component con taining; the other base. Then react* hydrolyzc, and you have a mixed dinueleotide. With these methods, Khorana says you can build u p in a stepwise and specific fashion higher polynucleo tides. And all these synthetic com pounds contain the typical naturallyoccurring C;{—G.-; internucleotide bonds. • Enzyme Degradation. When you know the exact composition of the polynucleotide, Khorana says, you can determine the mode of action of various enzymes such as nucleases and phos phodiesterases. Once you know that, you then can lise the enzymes with known modes of action on nucleic acids of unknown structures in much the same way that protein chemists have used proteolytic enzymes t o find the sequence of amino acids proteins. Khor ana points out. Khorana and his coworkers have already started this enzyme work us ing t h e well-characterized individual polynucleotides they have made b y the O C C activation technique. They have found, for example, that a snake venom diesterase degrades nucleotide polymers from the end having a free 3'-hydroxyl group and releases nucleoside-o* phosphates successively. Tfciey also have found an enzyme which degrades from the other end— the end having a free o'-hydroxyl and releases nudeoside-3' phosphates. T h e enzyme: a spleen diesterase. Thus, by identifying the nucleoside phos phates, chemists can determine nucleo side sequence in a particular polynu cleotide.
Add ing Liquids Reduce Power Costs τ—r τ—ι—ι—ι—ι— _£tu
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Toward Lower Pressure Drop Theoretical study of two-fluid system offers hope of reducing pumping costs on long distance pipelines XXJECTXXG water înio oil pipelines may lead to substantial savings in pumping costs, according to the results of a theoretical study in fluid dynamics at Research Council of Alberta, Edmonton, Alberta, Canada. A film of water next to the wail of a pipe can reduce pressure drop per foot as much a s one five hundredths, t h e study predicts. No one has been able to come even close to this potential achievement ( a factor of one twelfth is the best yet reported). But better control o f the location of the interface between water and oil and more complete wetting of the pipe wall by the water p h a s e may be major factors in approaching it, says G. W. Hodgson, head of petroleum research at the Council. Research in his group reveals that using the less viscous water in the area of maximum factional losses—at the pipe wall—should have the same effect as pumping the oil through a pipe moving in the same direction as the oil. Hence, energy loss at the walls should be greatly reduced; less driving force would b e needed to push the oil along at a given
flow rate, Hodgson nninAs o u t Hodgson, along with T. W. p . Russell (now with Union Carbide in Nffontreal) and M. E. Charles, analyzed "~the case of two immiscible fluids flowing concentrically in a circular pipe.** First they had to make several assumptions to handle the mathematics. For example, both fluids have the same density; viscosity of one is mucia greater than that of the other. Also, o i l in the pipe flows at the same volume rate with or without the water. Flow i s laminar, and the fluids are incompressible and Newtonian; the interface is sfcaarp with no mixing of phases. Although reduction in pressure drop should occur under these conditions, no one- has observed them, Hodgson points out. Nonetheless, he feels that th*e biggest problem is the physical one o f getting the two flows concentric. • Big Potential. Admittedly, this work is still theoretical, Hodgson says. But should it lead to a way to get lower pumping costs for heavy crude oils such as are in Alberta's tar sands. It could mean a lot to Canada's econ-
