片断: Chapter1 IntroductiontoBioorganic Chemistry "llmightbehelpful10rrminiliwrselves rcglariyofthesizcttbleincompletenessof ourunderstanding.notonlyofourselves(ts individualsandusilgroup,hutalsoofNature andtheworldaroundus. N.Hai-kerman Science183.907(1974) 1.1BasicConsiderations AmongthefirstpersonstodevelopbioorientedorganicprojectswasF.H. Westheimer.inthe1950s.Hewasprobabiythefirstphysicalorganic chemisttodoseriousstudiesot'biochemicalreactions.However.itwas onlytwentyvearslaterthatthefieldblossumedtowhatisnowaccepted asbioorganicchemistry. Bioorganicchemistrvisadisciplinethatisessentialtyconcernedwith theapplicationofthetoolsot'chemistrytotheunderstandingolbio- chemicalprocesses.Suchanunderstandingisot'tenachievedwiththeaid ot'moleculurmodelschemicallysynthesizedinthelaboratory.Thisallows a"sortingout"ofthemanyvariableparameterssimultaneouslyoperative withinthebiologicalsystem. Forexample.howdoesabiologicatmembranework?Onebuildsa simplemodelofknowncompositionsandstudiesasinglebehavior,such asaniontransportproperty.Howdoesthebrainwork?Thisisbyfarz, morecomplicatedsystemthanthepreviouscxample.Againonestudies singlesynapsesandsinglesynaptieconstituentsandthenasesthe observationstoconstructamodel. Organicchemistsdevelopsyntheticmethodologytobetterunderstand organicmechanismsandcreatenewcompounds.Ontheotherhand, biochemistsstudylifeprocessesbymeansofbiochemicalmethodology: enzymepurificationandassay,radioisotopictracerstudiesininvivo systems.Theformerpossessthemethodologytosynthesizebiological analogsbutoftenfailtoappreciatewhichsynthesiswouldberelevant. Thelatterpossessanappreciationofwhatwouldbeusefultosynthesize inthelaboratorybutnottheexpertisetopursuetheproblem.Theneed forthemultidisciplinaryapproachbecomesobvious,andthebioorganic chemistwilloftenhavetwolaboratories:oneforsynthesisandanother forbiologicalstudy.Anewdimensionresultsfromthiscombinationof chemicalandbiologicalsciences,thatis,theconceptofmodelbuildingto studyandsortoutthevariousparametersofacomplexbiologicalprocess. Bymeansofsimpleorganicmodels,manybiologicalreactionsaswell asthespecificityandefficiencyoftheenzymesinvolvedhavebeenrepro- ducedinthetesttube.Thesuccessofmanyofthesemodelsindicatesthe progressthathasbeenmadeinunderstandingthechemistryoperativein biologicalsystems.Extrapolationofthismultidisciplmarysciencetothe pathologicalstateisamajorthemeofthepharmaceuticalindustry- organicchemistsandpharmacologistsworking"sidebyside,"sothat bioorganicchemistryistobiochemistryandmedicinalchemistryisto pharmacology. Whatarethetoolsneededforbioorganicmodelstudies?Organicand physicalorganicchemicalprincipleswillprovide.bytheirverynature,the bestopportunitiesformodelbuilding-modelingmoleculareventsthat formthebasisoflife.Alargeportionoforganicchemistryhasbeen classicallydevotedtonaturalproducts.Manyofthoseresultshaveturned outtobewonderfultoolsforthediscoveryandcharacterizationofspecific moleculareventsinlivingsystems.Think,forinstance,ofthedevelop- mentofantibiotics,certainalkaloids,andthedesignofnewdrugsforthe medicineot'todayandtomorrow. Alllivingprocessesrequireenergy,whichisobtainedbyperforming chemicalreactionsinsidecells.Thesebiochemicalprocessesarebasedon chemicaldynamicsandinvolvereductionsandoxidations.Biological oxidationsarethusthemainsourceofenergytodriveanumberof endergonicbiologicaltransformations. Manyofthereactionsinvolvecombustionoffoodssuchassugarsand lipidstoproduceenergythatisusedforavarietyofessentialfunctions suchasgrowth,replication,maintenance,muscularwork.andheatpro- duction.Thesetransformationsarealsorelatedtooxygenuptake; breathingisabiochemicalprocessbywhichmolecularoxygenisreduced towater.Throughoutthesepathways,energyisstoredintheformof adenosnetriphosphate(ATP),anenergy-richcompoundknownasthe universalproductofenergetictr
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