Download Proteins – Amides from Amino Acids

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Chapter 26 and Chapter 28
Proteins – Amides from Amino Acids
• Aminoacidscontainabasicaminogroupand
anacidiccarboxylgroup
• Joinedasamidesbetweenthe¾NH2 ofone
aminoacidandthe¾CO2Htothenextamino
acid
• Chainswithfewerthan50unitsarecalled
peptides
• Protein:largechainsthathavestructuralor
catalyticfunctionsinbiology
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Proteins – Amides from Amino Acids
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Why this Chapter?
• Aminoacidsarethefundamentalbuilding
blocksofproteins
• Toseehowaminoacidsareincorporatedinto
proteinsandthestructuresofproteins
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26.1 Structures of Amino Acids
• Inneutralsolution,theCOOHisionizedand
theNH2 isprotonated
• Theresultingstructureshave“+”and“-”
charges(adipolarion,orzwitterion)
• Theyarelikeionicsaltsinsolution
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Chirality of Amino Acids
• Glycine,2-amino-aceticacid,isachiral
• Inalltheothers,thea carbonsoftheamino
acidsarecentersofchirality
• Thestereochemicalreferenceforaminoacids
istheFischerprojectionofL-serine
• ProteinsarederivedexclusivelyfromL-amino
acids
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Types of side chains
• Neutral:Fifteenofthetwentyhaveneutral
sidechains
• AspandGlu haveasecondCOOHandare
acidic
• Lys,Arg,Hishaveadditionalbasicamino
groupssidechains(theNintryptophanisa
veryweakbase)
• Cys,Ser,Tyr(OHandSH)areweakacidsthat
aregoodnucleophiles
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Histidine
• Containsanimidazoleringthatispartially
protonatedinneutralsolution
• Onlythepyridine-like,doublybonded
nitrogeninhistidineisbasic.Thepyrrole-like
singlybondednitrogenisnonbasicbecauseits
lonepairofelectronsispartofthe6p
electronaromaticimidazolering.
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Histidine
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Essential Amino Acids
• All20oftheaminoacidsarenecessaryfor
proteinsynthesis
• Humanscansynthesizeonly10ofthe20
• Theother10mustbeobtainedfromfood
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26.2 Amino Acids, the Henderson
Hasselbalch Equation, and Isoelectric Points
• Inacidicsolution,thecarboxylateandamine
areintheirconjugateacidforms,anoverall
cation
• Inbasicsolution,thegroupsareintheirbase
forms,anoverallanion
• Inneutralsolutioncationandanionformsare
present
• ThispHwheretheoverallchargeis0isthe
isoelectricpoint,pI
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26.2 Amino Acids, the Henderson
Hasselbalch Equation, and Isoelectric Points
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Titration Curves of Amino Acids
• IfpKa valuesforanaminoacidareknownthe
fractionsofeachprotonationstatecanbe
calculated(Henderson-Hasselbach Equation)
• pH=pKa +log[A-]/[HA]
• Thispermitsatitrationcurvetobecalculated
orpKa tobedeterminedfromatitrationcurve
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Titration Curves of Amino Acids
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26.4 Peptides and Proteins
• Proteinsandpeptidesareaminoacid
polymersinwhichtheindividualaminoacid
units,calledresidues,arelinkedtogetherby
amidebonds,orpeptidebonds
• Anaminogroupfromoneresidueformsan
amidebondwiththecarboxylofasecond
residue
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26.4 Peptides and Proteins
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Peptide Linkages
• Twodipeptidescanresultfromreactionbetween
AandS,dependingonwhichCOOHreactswith
whichNH2 wegetASorSA
• Thelong,repetitivesequenceof
¾N¾CH¾CO¾ atomsthatmakeupa
continuouschainiscalledtheprotein’sbackbone
• PeptidesarealwayswrittenwiththeN-terminal
aminoacid(theonewiththefree¾NH2 group)
ontheleftandtheC-terminalaminoacid(the
onewiththefree¾CO2Hgroup)ontheright
• Alanylserine isabbreviatedAla-Ser (orA-S),and
serylalanine isabbreviatedSer-Ala (orS-A)
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Peptide Linkages
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26.7 Peptide Synthesis
• Peptidesynthesisrequiresthatdifferent
amidebondsmustbeformedinadesired
sequence
• Thegrowingchainisprotectedatthecarboxyl
terminalandaddedaminoacidsareNprotected
• Afterpeptidebondformation,N-protectionis
removed
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26.7 Peptide Synthesis
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Carboxyl Protecting Groups
• Usuallyconvertedintomethylorbenzylesters
• Removedbymildhydrolysiswithaqueous
NaOH
• Benzylestersarecleavedbycatalytic
hydrogenolysisoftheweakbenzylicC–Obond
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Carboxyl Protecting Groups
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Amino Group Protection
• Anamidethatislessstablethantheprotein
amideisformedandthenremoved
• Thetert-butoxycarbonylamide(BOC)
protectinggroupisintroducedwithdi-tertbutyldicarbonate
• Removedbybrieftreatmentwith
trifluoroaceticacid
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Amino Group Protection
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Peptide Coupling
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26.9 Protein Structure
• Theprimarystructureofaproteinissimplythe
aminoacidsequence.
• Thesecondarystructureofaproteindescribes
howsegmentsofthepeptidebackboneorient
intoaregularpattern.
• Thetertiarystructuredescribeshowtheentire
proteinmoleculecoilsintoanoverallthreedimensionalshape.
• Thequaternarystructuredescribeshowdifferent
proteinmoleculescometogethertoyieldlarge
aggregatestructures
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a-Helix
• a-helixstabilizedbyH-bondsbetweenamide
N–HgroupsandC=Ogroupsfourresidues
awaya-helicalsegmentsintheirchains
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b-Pleated Sheet
• b-pleatedsheetsecondarystructureis
exhibitedbypolypeptidechainslinedupina
parallelarrangement,andheldtogetherby
hydrogenbondsbetweenchains
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Denaturation of Proteins
• Thetertiarystructureofaglobularproteinis
theresultofmanyintramolecularattractions
thatcanbedisruptedbyachangeofthe
environment,causingtheproteintobecome
denatured
• Solubilityisdrasticallydecreasedasinheating
eggwhite,wherethealbuminsunfoldand
coagulate
• Enzymesalsoloseallcatalyticactivitywhen
denatured
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Denaturation of Proteins
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Summary
• Wecoveredaminoacidsandtheirstructureatdifferent
pH’sbasedontheHenderson-HasselbalchEquation(26.126.2).
• Notresponsibleforsynthesisofaminoacids(26.3).
• Wediscussedthestructureofpeptidesandtheirlinkages
(26.4).
• Notresponsibleforaminoacidanalysisofpeptides(26.5)
orpeptidesequencing(26.6).
• Welearnedaboutpeptidesynthesis(26.7).
• Notresponsibleforautomatedpeptidesynthesis(26.8).
• Wediscussedproteinstructure(26.9).
• Notresponsibleforenzymesandcoenzymes(26.10).
• Forthefinalexampracticeproblemsfromtextbook:1-4,8,
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28.1 Nucleic acids
• Deoxyribonucleicacid(DNA)andribonucleic
acid(RNA)arechemicalcarriersofacell’s
geneticinformation
• Codedinacell’sDNAistheinformationthat
determinesthenatureofthecell,controlscell
growth,anddivision
• Nucleicacidderivativesareinvolvedas
phosphorylatingagentsinbiochemical
pathways
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Nucleotides and Nucleic acids
• Nucleicacidsarebiopolymersmadeof
nucleotides,whicharemadeofnucleosides
• Nucleosides are made of aldopentoses linked
to a purine or pyrimidine base
Heterocycles in DNA and RNA
• Adenine,guanine,cytosine,andthymineare
thefouraminespresentinDNA
• RNAcontainsuracilratherthanthymine
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Figure 28.1 - Structures of the Four deoxyribonucleotides and the Four
Ribonucleotides
Phosphodiester bonds
• Theylinknucleotidestogether
• Found between the 5’-hydroxyl group (5’ end)
on one nucleoside and the 3’-hydroxyl group
(3’ end) on the other side
• Nucleotidesinachainaresequenced
beginningatthe5’end
• Bases are identified in their order of
occurrence
• Abbreviations used are G,C,A,T (or U for
RNA)
• DNA sequence generally looks like TAGGCT
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Phosphodiester bonds
Base pairing in DNA
• In1953WatsonandCricknotedthatDNA
consistsoftwopolynucleotidestrands,
runninginoppositedirectionsandcoiled
aroundeachotherinadouble helix
• Strandsareheldtogetherbyhydrogenbonds
betweenspecificpairsofbases
• WheneveraGbaseoccursinonestrand,aC
baseoccursoppositeitintheotherstrand
• WhenanAbaseoccursinonestrand,aTbase
occursintheotherstrand
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Hydrogen bonding between base pairs in
the DNA double helix
Summary
• Onlycovered28.1and28.1.
• Forthefinalexampracticeproblemsfrom
textbook:1-3
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