Linked Life Data

18785763

Source:http://linkedlifedata.com/resource/pubmed/id/18785763

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
10
pubmed:dateCreated
2008-10-21
pubmed:abstractText
Naturally 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 alpha-aminoxy acids and explore their applications in the simulation of ion recognition and transport processes in living systems. Peptides constructed from alpha-aminoxy acids fold according to the following rules: (1) A strong intramolecular eight-membered-ring hydrogen bond forms between adjacent alpha-aminoxy acid residues (the alpha N-O turn). The chirality of the alpha-carbon, not the nature of the side chains, determines the conformation of this chiral N-O turn. (2) While homochiral oligomers of alpha-aminoxy acids form an extended helical structure (1.8 8 helix), heterochiral ones adopt a bent reverse turn structure. (3) In peptides of alternating alpha-amino acids and alpha-aminoxy acids, the seven-membered-ring intramolecular hydrogen bond, that is, the gamma-turn, is initiated by a succeeding alpha N-O turn. Thus, this type of peptide adopts a novel 7/8 helical structure. In investigating the potential applications of alpha-aminoxy acids, we have found that the amide NH units of alpha-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 alpha-aminoxy acids ideal building blocks for the construction of anion receptors. Indeed, we have constructed 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 alpha-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 alpha-aminoxy acids should lead to a broad range of applications in chemistry, biology, medicine, and materials science.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1520-4898
pubmed:author
pubmed:issnType
Electronic
pubmed:volume
41
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1428-38
pubmed:meshHeading
pubmed:year
2008
pubmed:articleTitle
Alpha-aminoxy acids: new possibilities from foldamers to anion receptors and channels.
pubmed:affiliation
Department of Chemistry, The University of Hong Kong, Pokfulam Road, Hong Kong, China.
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't