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Article: α-aminoxy acids: New possibilities from foldamers to anion receptors and channels

Titleα-aminoxy acids: New possibilities from foldamers to anion receptors and channels
Authors
Issue Date2008
PublisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/journals/achre4/about.html
Citation
Accounts Of Chemical Research, 2008, v. 41 n. 10, p. 1428-1438 How to Cite?
AbstractNaturally occurring peptides serve important functions as enzyme inhibitors, hormones, neurotransmitters, and immunomodulators in many physiological processes including metabolism, digestion, pain sensitivity, and the immune response. However, due to their conformational flexibility and poor bioavailability, such peptides are not generally viewed as useful therapeutic agents in clinical applications. In an effort to solve these problems, chemists have developed peptidomimetic foldamers, unnatural oligomeric molecules that fold into rigid and well-defined secondary structures mimicking the structures and biological functions of these natural peptides. We have designed peptidomimetic foldamers that give predictable, backbone-controlled secondary structures irrespective of the nature of the side chains. This Account presents our efforts to develop a novel class of peptidomimetic foldamers comprising α-aminoxy acids and explore their applications in the simulation of ion recognition and transport processes in living systems. Peptides constructed from α-aminoxy acids fold according to the following rules: (1) A strong intramolecular eight-membered-ring hydrogen bond forms between adjacent α-aminoxy acid residues (the α N-O turn). The chirality of the α-carbon, not the nature of the side chains, determines the conformation of this chiral N-O turn. (2) While homochiral oligomers of α-aminoxy acids form an extended helical structure (1.88 helix), heterochiral ones adopt a bent reverse turn structure. (3) In peptides of alternating α-amino acids and α-aminoxy acids, the seven-membered-ring intramolecular hydrogen bond, that is, the γ-turn, is initiated by a succeeding α N-O turn. Thus, this type of peptide adopts a novel 7/8 helical structure. In investigating the potential applications of α-aminoxy acids, we have found that the amide NH units of α-aminoxy acids are more acidic than are regular amide NH groups, which makes them better hydrogen bond donors when interacting with anions. This property makes α-aminoxy acids ideal building blocks for the construction of anion receptors. Indeed, we have constructued both cyclic and acyclic anion receptors that have strong affinities and good (enantio-)selectivities toward chloride (Cl-) and chiral carboxylate ions. Taking advantage of these systems' preference for Cl- ions, we have also employed α-aminoxy acid units to construct a synthetic Cl- channel that can mediate the passage of Cl- ions across cell membranes. Continued studies of these peptidomimetic systems built from α-aminoxy acids should lead to a broad range of applications in chemistry, biology, medicine, and materials science. (Chemical Equation Presented). © 2008 American Chemical Society.
Persistent Identifierhttp://hdl.handle.net/10722/168348
ISSN
2015 Impact Factor: 22.003
2015 SCImago Journal Rankings: 11.465
ISI Accession Number ID
References

 

DC FieldValueLanguage
dc.contributor.authorLi, Xen_US
dc.contributor.authorWu, YDen_US
dc.contributor.authorYang, Den_US
dc.date.accessioned2012-10-08T03:17:52Z-
dc.date.available2012-10-08T03:17:52Z-
dc.date.issued2008en_US
dc.identifier.citationAccounts Of Chemical Research, 2008, v. 41 n. 10, p. 1428-1438en_US
dc.identifier.issn0001-4842en_US
dc.identifier.urihttp://hdl.handle.net/10722/168348-
dc.description.abstractNaturally occurring peptides serve important functions as enzyme inhibitors, hormones, neurotransmitters, and immunomodulators in many physiological processes including metabolism, digestion, pain sensitivity, and the immune response. However, due to their conformational flexibility and poor bioavailability, such peptides are not generally viewed as useful therapeutic agents in clinical applications. In an effort to solve these problems, chemists have developed peptidomimetic foldamers, unnatural oligomeric molecules that fold into rigid and well-defined secondary structures mimicking the structures and biological functions of these natural peptides. We have designed peptidomimetic foldamers that give predictable, backbone-controlled secondary structures irrespective of the nature of the side chains. This Account presents our efforts to develop a novel class of peptidomimetic foldamers comprising α-aminoxy acids and explore their applications in the simulation of ion recognition and transport processes in living systems. Peptides constructed from α-aminoxy acids fold according to the following rules: (1) A strong intramolecular eight-membered-ring hydrogen bond forms between adjacent α-aminoxy acid residues (the α N-O turn). The chirality of the α-carbon, not the nature of the side chains, determines the conformation of this chiral N-O turn. (2) While homochiral oligomers of α-aminoxy acids form an extended helical structure (1.88 helix), heterochiral ones adopt a bent reverse turn structure. (3) In peptides of alternating α-amino acids and α-aminoxy acids, the seven-membered-ring intramolecular hydrogen bond, that is, the γ-turn, is initiated by a succeeding α N-O turn. Thus, this type of peptide adopts a novel 7/8 helical structure. In investigating the potential applications of α-aminoxy acids, we have found that the amide NH units of α-aminoxy acids are more acidic than are regular amide NH groups, which makes them better hydrogen bond donors when interacting with anions. This property makes α-aminoxy acids ideal building blocks for the construction of anion receptors. Indeed, we have constructued both cyclic and acyclic anion receptors that have strong affinities and good (enantio-)selectivities toward chloride (Cl-) and chiral carboxylate ions. Taking advantage of these systems' preference for Cl- ions, we have also employed α-aminoxy acid units to construct a synthetic Cl- channel that can mediate the passage of Cl- ions across cell membranes. Continued studies of these peptidomimetic systems built from α-aminoxy acids should lead to a broad range of applications in chemistry, biology, medicine, and materials science. (Chemical Equation Presented). © 2008 American Chemical Society.en_US
dc.languageengen_US
dc.publisherAmerican Chemical Society. The Journal's web site is located at http://pubs.acs.org/journals/achre4/about.htmlen_US
dc.relation.ispartofAccounts of Chemical Researchen_US
dc.subject.meshAcids - Chemistryen_US
dc.subject.meshAmino Acids - Chemistryen_US
dc.subject.meshAnions - Chemistryen_US
dc.subject.meshChloride Channels - Chemistryen_US
dc.subject.meshCircular Dichroismen_US
dc.subject.meshCrystallography, X-Rayen_US
dc.subject.meshMacrocyclic Compounds - Chemistryen_US
dc.subject.meshMagnetic Resonance Spectroscopyen_US
dc.subject.meshModels, Molecularen_US
dc.subject.meshMolecular Structureen_US
dc.subject.meshOxygen - Chemistryen_US
dc.subject.meshPeptides - Chemistryen_US
dc.titleα-aminoxy acids: New possibilities from foldamers to anion receptors and channelsen_US
dc.typeArticleen_US
dc.identifier.emailYang, D:yangdan@hku.hken_US
dc.identifier.authorityYang, D=rp00825en_US
dc.description.naturelink_to_subscribed_fulltexten_US
dc.identifier.doi10.1021/ar8001393en_US
dc.identifier.pmid18785763-
dc.identifier.scopuseid_2-s2.0-57349199922en_US
dc.identifier.hkuros167378-
dc.relation.referenceshttp://www.scopus.com/mlt/select.url?eid=2-s2.0-57349199922&selection=ref&src=s&origin=recordpageen_US
dc.identifier.volume41en_US
dc.identifier.issue10en_US
dc.identifier.spage1428en_US
dc.identifier.epage1438en_US
dc.identifier.isiWOS:000260254300020-
dc.publisher.placeUnited Statesen_US
dc.identifier.scopusauthoridLi, X=36072382700en_US
dc.identifier.scopusauthoridWu, YD=7406892738en_US
dc.identifier.scopusauthoridYang, D=7404800756en_US
dc.identifier.citeulike3251211-

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