Biomedical Engineering Reference
In-Depth Information
mirror-image.substrates..d-peptides.are.resistant.to.degradation.by.proteases,.making.them.
promising. drug. candidates.. d-amino. acids. have. been. computationally. modeled. (Nanda.
and. DeGrado. 2006). and. incorporated. into. l-peptides. to. improve. stability. (Rodriguez-
Granillo.et.al..2011)..Full.proteins.composed.entirely.of.d-amino.acids.could.be.very.useful.
for. the. synthesis. of. enantiomers. and. diastereomers. (Forster. and. Church. 2007),. or. as. a.
safety.mechanism.to.prevent.escaped.synthetic.biological.systems.from.interfering.with.
natural.life.
Natural. proteins. are. composed. of. 20. canonical. amino. acids,. which. among. them.
cover.a.considerable.amount.of.chemical.space..However,.artiicial.proteins.that.include.
noncanonical. amino. acids. could. potentially. perform. an. even. wider. range. of. functions..
Extensive. work. has. been. done. to. enable. the. global. or. site-speciic. incorporation. of.
noncanonical.amino.acids.into.proteins.and.has.been.extensively.reviewed.(e.g.,.Antonczak.
et. al.. 2011).. One. particularly. interesting. project. (Neumann. et. al.. 2010). used. a. modiied.
ribosome. that. recognized. nucleotide. quadruplet. codons. to. synthesize. artiicial. proteins.
containing. noncanonical. amino. acids.. Unlike. earlier. strategies. based. on. suppression. of.
the.amber.stop.codon,.this.method.can.allow.the.incorporation.of.multiple.noncanonical.
amino.acids.into.the.same.protein.
Peptoids,.or.N-substituted.glycines,.are.achiral,.protease-resistant.peptide.analogs..A.key.
advantage. of. peptoids. is. that. they. can. be. polymerized. by. a. convenient. and. economical.
submonomer. synthetic. method. (Burkoth. et. al.. 2003). that. allows. incorporation. of. any. of.
thousands. of. commercially. available. primary. amines.. An. engineered. ribosomal. system.
(Kawakami.et.al..2008b).has.also.been.developed.that.could.enable.selections.for.enzymatic.
peptoids. via. isolation. and. ampliication. of. encoding. mRNA.. Programming. of. polymer.
function.by.sequence-level.design.has.been.demonstrated.with.designed.peptoids..In.one.
example,. a. two-helix. bundle. was. designed. that. selectively. bound. zinc. with. nanomolar.
afinity.(Lee.et.al..2008)..Thiol.and.imidazole.side.chains.(inspired.by.the.cysteines. and.
histidines.used.to.bind.zinc.in.proteins).were.positioned.to.bind.zinc.only.of.the.peptoid.
assumed. the. target. structure.. In. another. study,. two. peptoid. polymers. were. reported. to.
form.two-dimensional.crystalline.sheets.in.aqueous.solution.(Nam.et.al..2010)..When.mixed.
at.a.1:1.ratio,.the.two.36-mers.spontaneously.formed.a.2.7.nm-thick.bilayer..Assembly.was.
driven.by.the.burial.of.hydrophobic.side.chains.and.pairing.of.positively.and.negatively.
charged.side.chains.and.did.not.require.a.phase.interface.as.a.template..Fusing.an.achiral.
small. molecule. catalyst. to. a. structured. peptoid. resulted. in. enantioselective. catalysis,.
which.depended.on.the.handedness.of.the.peptoid.used.(Maayan.et.al..2009).
Another. promising. class. of. foldamers. is. the. β-peptides.. As. opposed. to. standard. α.
amino.acids,.in.which.the.amino.group.is.bonded.to.the.α.carbon,.in.β.amino.acids,.the.
amino. group. is. bonded. to. the. β. carbon.. The. side. chain. can. branch. off. of. the. α. carbon.
(β
2
-peptides).or.the.β.carbon.(β
3
-peptides)..β
3
-peptide.foldamers.have.been.shown.to.adopt.
helical.secondary.structure.(Appella.et.al..1997).and.cooperative.noncovalent.quaternary.
structure.(Qiu.et.al..2006).but.are.more.dificult.than.peptoids.to.synthesize.
Both.β-peptides.(Porter.et.al..2002).and.peptoids.(Chongsiriwatana.et.al..2008).can.mimic.
the.fold.and.function.of.antimicrobial.peptides,.with.greatly.reduced.susceptibility.to.in.
vivo.degradation..Despite.the.lack.of.a.natural.structural.knowledge.base.against.which.
to.it.parameters,.computational.methods.developed.for.protein.structure.prediction.and.
design. are. being. extended. for. use. with. β-peptides. (Shandler. et. al.. 2010). and. peptoids.
(Butterfoss.et.al..2009).to.facilitate.future.designs..Computational.design.was.recently.used.
to.build.a.self-assembling.β-peptide.hexameric.bundle.(Korendovych.et.al..2010).
Enzyme-like. catalysts. are. also. emerging. from. the. ield. of. supramolecular. chemistry,.
which. adopts. the. noncovalent. interaction-based. speciicity. strategy. that. is. so. successful.
