作者：H.Dugas 日期：2019-06-17 15:00:49
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