A Leucyl-tRNA Synthetase Urzyme: Authenticity of tRNA Synthetase Catalytic Activities and Promiscuous Phosphorylation of Leucyl-5′AMP

Aminoacyl-tRNA synthetase (aaRS)/tRNA cognate pairs translate the genetic code by synthesizing specific aminoacyl-tRNAs that are assembled on messenger RNA by the ribosome. Deconstruction of the two distinct aaRS superfamilies (Classes) has provided conceptual and experimental models for their early evolution. Urzymes, containing ~120–130 amino acids excerpted from regions where genetic coding sequence complementarities have been identified, are key experimental models motivated by the proposal of a single bidirectional ancestral gene. Previous reports that Class I and Class II urzymes accelerate both amino acid activation and tRNA aminoacylation have not been extended to other synthetases. We describe a third urzyme (LeuAC) prepared from the Class IA Pyrococcus horikoshii leucyl-tRNA synthetase. We adduce multiple lines of evidence for the authenticity of its catalysis of both canonical reactions, amino acid activation and tRNA^Leu aminoacylation. Mutation of the three active-site lysine residues to alanine causes significant, but modest reduction in both amino acid activation and aminoacylation. LeuAC also catalyzes production of ADP, a non-canonical enzymatic function that has been overlooked since it first was described for several full-length aaRS in the 1970s. Structural data suggest that the LeuAC active site accommodates two ATP conformations that are prominent in water but rarely seen bound to proteins, accounting for successive, in situ phosphorylation of the bound leucyl-5′AMP phosphate, accounting for ADP production. This unusual ATP consumption regenerates the transition state for amino acid activation and suggests, in turn, that in the absence of the editing and anticodon-binding domains, LeuAC releases leu-5′AMP unusually slowly, relative to the two phosphorylation reactions.     

RNA Aminoacylation Mediated by Sequential Action of Two Ribozymes and a Nonactivated Amino Acid

In the transition from the RNA world to the modern DNA/protein world, RNA‐catalyzed aminoacylation might have been a key step towards early translation. A number of ribozymes capable of aminoacylating their own 3′ termini have been developed by in vitro selection. However, all of those catalysts require a previously activated amino acid—typically an aminoacyl‐AMP—as substrate. Here we present two ribozymes connected by intermolecular base pairing and carrying out the two steps of aminoacylation: ribozyme 1 loads nonactivated phenylalanine onto its phosphorylated 5′ terminus, thereby forming a high‐energy mixed anhydride. Thereafter, a complex of ribozymes 1 and 2 is formed by intermolecular base pairing, and the “activated” phenylalanine is transferred from the 5′ terminus of ribozyme 1 to the 3′ terminus of ribozyme 2. This kind of simple RNA aminoacylase complex was engineered from previously selected ribozymes possessing the two required activities. RNA aminoacylation with a nonactivated amino acid as described here is advantageous to RNA world scenarios because initial amino acid activation by an additional reagent (in most cases, ATP) and an additional ribozyme would not be necessary.     

A new strategy for the synthesis of dinucleotides loaded with glycosylated amino acids--investigations on in vitro non-natural amino acid mutagenesis for glycoprotein synthesis

The in vitro non-natural amino acid mutagenesis method provides the opportunity to introduce non-natural amino acids site-specifically into proteins. To this end, a chemically synthesised aminoacylated dinucleotide is enzymatically ligated to a truncated suppressor transfer RNA. The loaded suppressor tRNA is then used in translation reactions to read an internal stop codon. Here we report an advanced and general strategy for the synthesis of the aminoacyl dinucleotide. The protecting group pattern developed for the dinucleotide facilitates highly efficient aminoacylation, followed by one-step global deprotection. The strategy was applied to the synthesis of dinucleotides loaded with 2-acetamido-2-deoxy-glycosylated amino acids, including N- and O-beta-glycosides and O- and C-alpha-glycosides of amino acids, thus enabling the extension of in vitro non-natural amino acid mutagenesis towards the synthesis of natural glycoproteins of high biological interest. We demonstrate the incorporation of the glycosylamino acids--although with low suppression efficiency--into the human interleukin granulocyte-colony stimulating factor (hG-CSF), as verified by the ELISA technique.     

The introduction of alkyl,ester, carboxylate,amino, hydroxyl,and phosphate functional groups to the surface of polyethylene

The surface of polyethylene was derivatized with ester, carboxylate, amino, hydroxyl, and phosphate functional groups. α, ω bifunctional alkanes, containing on one end a primary amine, were coupled to oxidized polyethylene through an amide linkage. Polyethylene was first oxidized with chromic acid, the carboxylate groups were converted to the acyl chloride with phosphorus pentachloride, and then reacted with a primary amine to give the covalently bound amide. The copposing ends of the bifunctional alkanes were the methyl, tertiary amine, ester, and hydroxyl groups. The ester was converted to the carboxylate by acid cleavage and the hydroxyl group converted to the phosphate by treatment first with phosphorus oxychloride and then aqueous base. Attenuated total reflection FTIR, XPS, and pH-dependent contact angle wetting were used to characterize the surfaces. The FTIR data were used to confirm the formation of the amide and to detect an undesired carboxylate/ammonium ion complex formed in the presence of trace amounts of water. XPS data were used to confirm expected changes in elemental composition and to provide quantitative estimates of the yields. Oxidation of the polyethylene introduced 5 × 10¹⁴ carboxylate groups/cm² in the 25 Å XPS sampling depth. Of these, up to 98% could be converted to the amide. The advancing contact angle data confirmed the acid/base behavior of the functional groups.     

Cloning of Flax Oleic Fatty Acid Desaturase and Its Expression in Yeast

Fatty acid desaturases dehydrogenate acyl chains, which results in the formation of a double bond. Using PCR on flax genomic DNA, we cloned a putative Δ12 fatty acid desaturase (Fad2) gene encoding a 378 amino acid protein. Heterologous expression of this protein in yeast as an N-terminal fusion to GFP showed its localization within endoplasmic reticulum. Analysis of membrane lipids revealed the production of dienoic fatty acids, decreased levels of FAD2 substrates and an increased concentration of longer fatty acids. Higher peroxidation of lipids in FAD2-containing strains is not reflected by any visible phenotype in YPD medium. However, FAD2-containing strains with deleted superoxide dismutase genes exhibited significant growth reductions under oxidative stress.     

Can Phosphate‐Branched RNA Persist under Physiological Conditions?

A 2′‐O‐methyl‐RNA oligonucleotide containing a single free 2′‐OH group flanking a branching phosphotriester linkage was prepared as a model for phosphate‐branched RNA by using an orthogonally protected dimeric phosphoramidite building block in solid‐phase synthesis. The strategy allows the synthesis of phosphate‐branched oligonucleotides, the three branches of which may be of any desired sequence. Hydrolytic reactions of the phosphotriester linkages in such oligonucleotides were studied at physiological pH in the presence (and absence) of various complementary oligonucleotides. The fully hybridized oligonucleotide model is an order of magnitude more stable than its single‐stranded counterpart, which, in turn, is an order of magnitude more stable than its trinucleoside phosphotriester core lacking any oligonucleotide arms. Furthermore, kinked structures obtained by hybridizing the phosphate‐branched oligonucleotide with partially complementary oligonucleotides are three to five times more stable than fully double‐stranded ones and only approximately three times less stable than the so‐called RNA X structure, which has been postulated to incorporate an RNA phosphotriester linkage. The results indicate that when the intrinsically unstable RNA phosphotriester linkage is embedded in an oligonucleotide of appropriate tertiary structure, its half‐life can be at least several hours.     

Triplex-Forming Peptide Nucleic Acids with Extended Backbones

Peptide nucleic acid (PNA) forms a triple helix with double-stranded RNA (dsRNA) stabilized by a hydrogen-bonding zipper formed by PNA's backbone amides (N−H) interacting with RNA phosphate oxygens. This hydrogen-bonding pattern is enabled by the matching ∼5.7 Å spacing (typical for A-form dsRNA) between PNA's backbone amides and RNA phosphate oxygens. We hypothesized that extending the PNA's backbone by one −CH₂− group might bring the distance between PNA amide groups closer to 7 Å, which is favourable for hydrogen bonding to the B-form dsDNA phosphate oxygens. Extension of the PNA backbone was expected to selectively stabilize PNA-DNA triplexes compared to PNA-RNA. To test this hypothesis, we synthesized triplex-forming PNAs that had the pseudopeptide backbones extended by an additional −CH₂− group in three different positions. Isothermal titration calorimetry measurements of the binding affinity of these extended PNA analogues for the matched dsDNA and dsRNA showed that, contrary to our structural reasoning, extending the PNA backbone at any position had a strong negative effect on triplex stability. Our results suggest that PNAs might have an inherent preference for A-form-like conformations when binding double-stranded nucleic acids. It appears that the original six-atom-long PNA backbone is an almost perfect fit for binding to A-form nucleic acids.     

光学纯氨基酸的研究进展

氨基酸能参与多种多样的生命活动，此外它还是合成多种药物的重要中间体。大多数氨基酸都有一个或一个以上的手性中心，手性不同其生物活性也不同。因为生命活动对不同的氨基酸会有立体选择性，所以光学纯氨基酸在制药与食品行业有着非常重要的应用。本文综述了近些年国内外光学纯氨基酸的研究进展。     

Fluorobenzene Nucleobase Analogues for Triplex-Forming Peptide Nucleic Acids

2,4-Difluorotoluene is a nonpolar isostere of thymidine that has been used as a powerful mechanistic probe to study the role of hydrogen bonding in nucleic acid recognition and interactions with polymerases. In the present study, we evaluated five fluorinated benzenes as nucleobase analogues in peptide nucleic acids designed for triple helical recognition of double helical RNA. We found that analogues having para and ortho fluorine substitution patterns (as in 2,4-difluorotoluene) selectively stabilized Hoogsteen triplets with U−A base pairs. The results were consistent with attractive electrostatic interactions akin to non-canonical F to H−N and C−H to N hydrogen bonding. The fluorinated nucleobases were not able to stabilize Hoogsteen-like triplets with pyrimidines in either G−C or A−U base pairs. Our results illustrate the ability of fluorine to engage in non-canonical base pairing and provide insights into triple helical recognition of RNA.     

Flexizymes: their evolutionary history and the origin of catalytic function

Transfer RNA (tRNA) is an essential component of the cell's translation apparatus. These RNA strands contain the anticodon for a given amino acid, and when "charged" with that amino acid are termed aminoacyl-tRNA. Aminoacylation, which occurs exclusively at one of the 3'-terminal hydroxyl groups of tRNA, is catalyzed by a family of enzymes called aminoacyl-tRNA synthetases (ARSs). In a primitive translation system, before the advent of sophisticated protein-based enzymes, this chemical event could conceivably have been catalyzed solely by RNA enzymes. Given the evolutionary implications, our group attempted in vitro selection of artificial ARS-like ribozymes, successfully uncovering a functional ribozyme (r24) from an RNA pool of random sequences attached to the 5'-leader region of tRNA. This ribozyme preferentially charges aromatic amino acids (such as phenylalanine) activated with cyanomethyl ester (CME) onto specific kinds of tRNA. During the course of our studies, we became interested in developing a versatile, rather than a specific, aminoacylation catalyst. Such a ribozyme could facilitate the preparation of intentionally misacylated tRNAs and thus serve a convenient tool for manipulating the genetic code. On the basis of biochemical studies of r24, we constructed a truncated version of r24 (r24mini) that was 57 nucleotides long. This r24mini was then further shortened to 45 nucleotides. This ribozyme could charge various tRNAs through very simple three-base-pair interactions between the ribozyme's 3'-end and the tRNA's 3'-end. We termed this ribozyme a "flexizyme" (Fx3 for this particular construct) owing to its flexibility in addressing tRNAs. To devise an even more flexible tool for tRNA acylation, we attempted to eliminate the amino acid specificity from Fx3. This attempt yielded an Fx3 variant, termed dFx, which accepts amino acid substrates having 3,5-dinitrobenzyl ester instead of CME as a leaving group. Similar selection attempts with the original phenylalanine-CME and a substrate activated by (2-aminoethyl)amidocarboxybenzyl thioester yielded the variants eFx and aFx (e and a denote enhanced and amino, respectively). In this Account, we describe the history and development of these flexizymes and their appropriate substrates, which provide a versatile and easy-to-use tRNA acylation system. Their use permits the synthesis of a wide array of acyl-tRNAs charged with artificial amino and hydroxy acids. In parallel to these efforts, we initiated a crystallization study of Fx3 covalently conjugated to a microhelix RNA, which is an analogue of tRNA. The X-ray crystal structure, solved as a co-complex with phenylalanine ethyl ester and U1A-binding protein, revealed the structural basis of this enzyme. Most importantly, many biochemical observations were consistent with the crystal structure. Along with the predicted three regular-helix regions, however, the flexizyme has a unique irregular helix that was unexpected. This irregular helix constitutes a recognition pocket for the aromatic ring of the amino acid side chain and precisely brings the carbonyl group to the 3'-hydroxyl group of the tRNA 3'-end. This study has clearly defined the molecular interactions between Fx3, tRNA, and the amino acid substrate, revealing the fundamental basis of this unique catalytic system.     

微波辅助法合成手性β-氨基酸

手性β-氨基酸是一类在药物开发和生物研究中具有广泛应用的中间体,尝试了以L-天冬氨酸为手性源合成手性β-氨基酸的研究,其合成方法：首先对天冬氨酸进行氨基保护,然后利用微波,高效地合成（ S）-N-保护的丝氨酸-γ-内酯,最后通过傅克反应,合成具有芳香性的手性β氨基酸。具有路线短、操作方便、绿色经济等优点,适合工业化大生产。     

Fatty Acyl Synthetases and Thioesterases in Plant Lipid Metabolism: Diverse Functions and Biotechnological Applications

Plants use fatty acids to synthesize acyl lipids for many different cellular, physiological, and defensive roles. These roles include the synthesis of essential membrane, storage, or surface lipids, as well as the production of various fatty acid-derived metabolites used for signaling or defense. Fatty acids are activated for metabolic processing via a thioester linkage to either coenzyme A or acyl carrier protein. Acyl synthetases metabolically activate fatty acids to their thioester forms, and acyl thioesterases deactivate fatty acyl thioesters to free fatty acids by hydrolysis. These two enzyme classes therefore play critical roles in lipid metabolism. This review highlights the surprisingly complex and varying roles of fatty acyl synthetases in plant lipid metabolism, including roles in the intracellular trafficking of fatty acids. This review also surveys the many specialized fatty acyl thioesterases characterized to date in plants, which produce a great diversity of fatty acid products in a tissue-specific manner. While some acyl thioesterases produce fatty acids that clearly play roles in plant-insect or plant-microbial interactions, most plant acyl thioesterases have yet to be fully characterized both in terms of their substrate specificities and their functions. The biotechnological applications of plant acyl thioesterases and synthetases are also discussed, as there is significant interest in these enzymes as catalysts for the sustainable production of fatty acids and their derivatives for industrial uses.     

Amino acid oxidase‐catalysed resolution and Pictet–Spengler reaction towards chiral and rigid unnatural amino acids

BACKGROUND: The biosynthesis of structurally complex isoquinoline alkaloids and other natural products occurs via aromatic amino acids such as tyrosine, and chiral and rigid amino acids. These structures are also key building blocks of many active pharmaceutical ingredients. The aim of this work was the exploration of a rapid and straightforward route to chiral 6‐hydroxy‐1,2,3,4‐tetrahydroisoquinoline‐3‐carboxylic acid. RESULTS: The preparation of (S)‐meta‐tyrosine from racemic meta‐tyro‐ sine with aminoacidoxidase has been developed with ee > 99% and 88% yield. The combination of this resolution with a subsequent Pictet–Spengler reaction enables straightforward and versatile access to chiral (S)‐6‐hydroxy‐1,2,3,4‐tetrahydroisoquinoline‐3‐carboxylic acid in 30% yield. CONCLUSIONS: This new short chemoenzymatic route to (S)‐6‐hydroxy‐1,2,3,4‐tetrahydroisoquinoline‐3‐carboxylic acid from commercially available DL‐m‐tyrosine is more convenient than other chemical procedures and establishes a new link between the pool of easily accessible racemic aromatic amino acids and the corresponding chiral rigidified amino acids, which are of interest as structural elements of many active pharmaceutical ingredients. These results facilitate synthetic access to a range of active pharmaceutical ingredients and metabolites in chiral form from the oxidation of amino acids. This advances the opportunities to study the molecular interactions with enzymes, receptors and effectors more precisely than with the racemic forms. Copyright © 2007 Society of Chemical Industry     

Preparation and properties of high‐performance recyclable ethylene propylene diene rubber

To obtain high‐performance recyclable ethylene propylene diene rubber (EPDM), EPDM was chemically functionalized as follows: EPDM was grafted with citraconic acid (CCA) by radical melt polymerization to produce a grafted EPDM (EPDM‐g‐CCA), and EPDM‐g‐CCA was reacted with various amino acids by melt condensation reaction to give amidated copolymers (EPDM‐g‐CCA‐2‐Am, EPDM‐g‐CCA‐7‐Am, and EPDM‐g‐CCA‐12‐Am, where the n indicates the carbon number of amino acid), and then ionomers (EPDM‐g‐CCA/n‐Am/Io) were prepared by melt reaction of EPDM‐g‐CCA/n‐Ams with Zinc oxide (ZnO)/zinc stearate (ZnSt). The mechanical properties/compression set (CS) resistance (elasticity)/recyclability of pristine EPDM, EPDM‐g‐CCA, EPDM‐g‐CCA/n‐Am, and ionomers sheet samples were compared. The tensile strength/modulus, tear strength, and elasticity of samples were mostly increased in the order of ionomers>EPDM‐g‐CCA/n‐Ams>EPDM‐g‐CCA>pristine EPDM. The properties of ionomers increased significantly with increasing the carbon number in amino acid up to seven, and then levelled off or decreased a little. The tensile strength/elasticity (compression set resistance) of recyclable ionomer (EPDM‐g‐CCA/7‐Am/Io) was found to be ～9.42/～2.31 times of pristine EPDM, respectively. © 2015 Wiley Periodicals, Inc. J. Appl. Polym. Sci. 2015 , 132, 42718.     

Enhanced stability of recombinant keratinocyte growth factor by mutagenesis

Native sequence keratinocyte growth factor (KGF) is fairly unstable, as manifested by the loss of the monomeric native protein accompanied by the accumulation of aggregated species during storage at moderate temperatures. Several different types of analogs were generated and the storage stability of the protein assessed. In the first type of analog one or more of the five cysteinyl residues in KGF were replaced; in the second class the N-terminal residues that included the first disulfide bond were deleted. Both of these types of analogs involved removal of the disulfide bond between cysteines 1 and 15. The third group involved mutating one of the basic amino acids located in a cluster of positive charges (involved in heparin binding) around Arg144 to a neutral or acidic amino acyl residue. Among the cysteine replacement analogs, the double mutation of Cys1 and 15 to Ser resulted in significantly increased stability without compromising the mitogenic activity, while Cys to Ser mutations at other positions were either destabilizing or had no effect. Deletion of the 15, 23 or 27 N-terminal amino acyl residues also increased the stability of the protein. The activity of the analogs was not affected by the deletion of 15 or 23 amino acids, but it was significantly decreased upon removal of the 27 N-terminal amino acyl residues. Much greater stability was achieved by mutation of the basic amino acids, especially Arg144, to Glu or Gln, but this increase in stability was accompanied by large decrease in activity. The analog with the 23 N-terminal amino acyl residues deleted represents one of the best compromises between increased stability and retention of activity.     

Helix-sense-selective polymerization of achiral substituted acetylene in chiral micelles for preparing optically active polymer nanoparticles: Effects of chiral emulsifiers

This paper reports helix-sense-selective polymerizations (HSSPs) of achiral acetylene monomer performed in chiral micelles, by which optically active helical polymer emulsions were directly obtained. The chiral micelles were constructed by chiral emulsifiers, in which achiral acetylene underwent HSSPs in the presence of catalyst [(nbd)RhCl]₂. The chiral emulsifiers possessed different alkyl chain lengths and different amino acid groups, and their effects on HSSPs were investigated in detail. The obtained polymer emulsions were characterized by TEM, circular dichroism and UV–vis absorption spectroscopy techniques. It is demonstrated that the polymer chains constructing the emulsions adopted helical structures of predominantly one-handed screw sense, from which the emulsions exhibited remarkable optical activity.     

Altered acyl chain length specificity of Rhizopus delemar lipase through mutagenesis and molecular modeling

The acyl binding site of Rhizopus delemar prolipase and mature lipase was altered through site-directed mutagenesis to improve lipase specificity for short-or medium-chain length fatty acids. Computer-generated structural models of R. delemar lipase were used in mutant protein design and in the interpretation of the catalytic properties of the resulting recombinant enzymes. Molecular dynamics simulations of the double mutant, val209trp+phe112trp, predicted that the introduction of trp112 and trp209 in the acyl binding groove would sterically hinder the docking of fatty acids longer than butyric acid. Assayed against a mixture of triacylglycerol substrates, the val209trp+phe112trp mature lipase mutant showed an 80-fold increase in the hydrolysis of tributyrin relative to the hydrolysis of tricaprylin while no triolein hydrolysis was detected. By comparison, the val94Trp mutant, predicted to pose steric or geometric constraints for docking fatty acids longer than caprylic acid in the acyl binding groove, resulted in a modest 1.4-fold increase in tricaprylin hydrolysis relative to the hydrolysis of tributyrin. Molecular models of the double mutant phe95asp+phe214arg indicated the creation of a salt bridge between asp95 and arg214 across the distal end of the acyl binding groove. When challenged with a mixture of triacylglycerols, the phe95asp+phe214arg substitutions resulted in an enzyme with 3-fold enhanced relative activity for tricaprylin compared to triolein, suggesting that structural determinants for medium-chain length specificity may reside in the distal end of the acyl binding groove. Attempts to introduce a salt bridge within 8 Å of the active site by the double mutation leu146lys+ser115asp destroyed catalytic activity entirely. Similarly, the substitution of polar Gln at the rim of the acyl binding groove for phe 112 largely eliminated catalytic activity of the lipase.     

A mutant D-amino acid aminotransferase with broad substrate specificity: construction by replacement of the interdomain loop Pro119- Arg120-Pro121 by Gly-Gly-Gly

D-amino acid aminotransferase (EC 2.6.1.21) catalyzes the interconversion of various D-amino acids and 2-oxo acids. Each homodimer subunit consists of two domains, which are connected by a single loop, Asn118-Pro119-Arg120-Pro121. The loop has no direct contact with the active site region or the cofactor, pyridoxal 5'- phosphate. We attempted to increase the conformational flexibility of this loop through a triple glycine substitution. The resultant mutant P119G-R120G-P121G has features clearly different from the wild-type enzyme under overall as well as half-reaction conditions. The pre- steady-state kinetic analyses of half reactions showed that the mutant enzyme has kmax values higher than the wild-type enzyme towards most D- amino acids examined. A concomitant decrease in substrate affinity (1/Kd), particularly for acidic amino acids, was also observed. A putative binding site for the distal carboxyl group of acidic amino acids in the wild-type enzyme was incidentally displaced by the loop mutation, indicating a functional linkage between the interdomain loop and the active site region. This study has exemplified the usefulness of engineering relatively distant loops as a means to modify substrate specificity of an enzyme.      

Alpha-aminoxy acids: new possibilities from foldamers to anion receptors and channels

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.