Amino acids, L-, D-, and

Fig. 3. (a) Chemical stmcture of a synthetic cycHc peptide composed of an alternating sequence of D- and L-amino acids. The side chains of the amino acids have been chosen such that the peripheral functional groups of the dat rings are hydrophobic and allow insertion into Hpid bilayers, (b) Proposed stmcture of a self-assembled transmembrane pore comprised of hydrogen bonded cycHc peptides. The channel is stabilized by hydrogen bonds between the peptide backbones of the individual molecules. These synthetic pores have been demonstrated to form ion channels in Hpid bilayers (71). 

Enzymatic hydrolysis is also used for the preparation of L-amino acids. Racemic D- and L-amino acids and their acyl-derivatives obtained chemically can be resolved enzymatically to yield their natural L-forms. Aminoacylases such as that from Pispergillus OTj e specifically hydrolyze L-enantiomers of acyl-DL-amino acids. The resulting L-amino acid can be separated readily from the unchanged acyl-D form which is racemized and subjected to further hydrolysis. Several L-amino acids, eg, methionine [63-68-3], phenylalanine [63-91-2], tryptophan [73-22-3], and valine [72-18-4] have been manufactured by this process in Japan and production costs have been reduced by 40% through the appHcation of immobilized cell technology (75). Cyclohexane chloride, which is a by-product in nylon manufacture, is chemically converted to DL-amino-S-caprolactam [105-60-2] (23) which is resolved and/or racemized to (24)... 

D- or L-amino acids, but a given helix must be composed entirely of amino acids of one configuration. a-Helices cannot be formed from a mixed copolymer of D- and L-amino acids. An a-helix composed of D-amino acids is left-handed. 

D. Mass Spectra of 1V-PFP Isopropyl Esters of D and L Amino Acids The molecular ion is usually not observed but can be deduced by adding 87 (COOC3H7) Daltons to the most abundant, high-mass ion. Masses 69 (CF3) and 119 (C2F5) may also be observed.2... 

Cyclic artificial polypeptides comprised of alternating d and l amino acids were recently synthesized and self-assembled into nanotubes exhibiting lengths of 1000-1500 A, formed at an air-water interface [34,35],... 

El, Ed electrophilic peptide fragments consisting of 17 D- and L-amino acid residues T condensation product formed from E and N TlL, Tdd peptide containing only L- or D-amino acid sequences Tdl peptide containing both amino acid species... 

The topical homochirality problem is presently being investigated in several research laboratories across the world. One new object of study is systems with eutectic mixtures. The addition of chiral dicarboxylic acids that co-crystallise with chiral amino acids to aqueous mixtures of d- and L-amino acids allows tuning of the eutectic composition of the amino acids in several cases, these systems yield new eutectic compositions of 98% ee or higher. Thus, solid mixed crystals with a ratio... 

JM Manning. Determination of D- and L-amino acid residues in peptides. Use of tritiated hydrochloric acid to correct for racemization during acid hydrolysis. J Am Chem Soc 92, 7449, 1970. 

PE Hare, E Gil-Av. Separation of d- and l- amino acids by liquid chromatography use of chiral eluants. Science 204, 1226, 1979. 

JM Manning, S Moore. Determination of d- and L-amino acids by ion-exchange chromatography as l-d and l-l- dipeptides. J Biol Chern 243, 5591, 1968. 

AR Mitchell, SBH Kent, IC Chu, RB Merrifield. Quantitative determination of d-and L-amino acids by reaction with ferf-butoxycarbonyl-L-leucine A-hydroxysuccin-imide ester and chomatographic separation as d,l and l,l dipeptides. Anal Chern 50, 637, 1978. 

Amino acids D- and L-amino acid oxidases Hydrogen peroxide Platinum... 

D-Amino acid oxidase (EC 1.4.3.3) extracted from sheep kidney possesses low selectivity and at pH 8-9 will oxidise many D amino acids, whereas L-amino acid oxidase (EC 1.4.3.2) from snake venom (Crotalus adaman-teus) at pH 8-9 catalyses the oxidation of many L amino acids. However, as these enzymes show different reactivity towards different amino acids, the results for a sample that contains several D and L amino acids may be difficult to interpret. The use of these enzymes is therefore only recommended for the measurement of one isomer of an isolated amino acid. They may also be used to remove an unwanted isomer from a sample containing both to allow subsequent measurement of the other. 

Amperometric biosensors incorporating certain enzymes on the electrode for the determination of D- and L-amino acids were investigated. The parameters included enzyme immobilization procedure, composition of the immobilizing matrix, amount of enzyme,... 

OPA in combination with chiral thiols is one method used to determine amino acid enantiomers. A highly fluorescent diastereomeric isoindole is formed and can be separated on a reverse-phase column. Some of these chiral thiols include N-acetyl-L-cysteine (NAC), N-tert-butyloxy-carbonyl- L-cysteine (Boc-L-Cys), N-isobutyryl- L-cysteine (IBLC), and N-isobutyryl- D -cysteine (IBDC). Replacing OPA-IBLC with OPA-IBDC causes a reversal in the elution order of the derivatives of D- and L-amino acids on an ODS column (Hamase et al., 2002). Nimura and colleagues (2003) developed a novel, optically active thiol compound, N-(tert-butylthiocarbamoyl)- L-cysteine ethyl ester (BTCC). This reagent was applied to the measurement of D-Asp with a detection limit of approximately 1 pmol, even in the presence of large quantities of L-ASP. 

CSPs and chiral mobile phase additives have also been used in the separation of amino acid enantiomers. Another technique that should be mentioned is an analysis system employing column-switching. D-and L- amino acids are first isolated as the racemic mixture by reverse-phase HPLC. The isolated fractions are introduced to a second column (a CSP or a mobile phase containing a chiral selector) for separation of enantiomers. Long et al. (2001) applied this technique to the determination of D- and L-Asp in cell culture medium, within cells and in rat blood. 

TAT liposomes remain intact within one hour of translocation and slowly migrate through the cell, bypassing the endocytic pathway, to the perinuclear zone where they disintegrate (95). The mechanism utilized by TAT to migrate across the membrane was thought to be energy independent because it operates at similar rates at both 4°C and 37°C (95,96). Cell entry by TAT is also unhindered by metabolic inhibitors such as sodium azide or iodoacetamide (97). Peptides constructed of both the d and l amino acids of Antp can be detected intracellularly, the inference of which is that no specific receptor was required because both isomers had equal potential (98,99). 

Resolution of d- and L-Amino Acid Derivatives 5.03.5.4.1 Resolution of racemic amino acid esters... 

Here is an important point almost all chiral amino acids that occur naturally in proteins throughout all of nature have L-stereochemistry. Why has nature uniquely selected L-amino acids for the construction of proteins No one knows for sure. In passing, we note that D-amino acids do occur in some living systems. The cell walls of bacteria possess both d- and L-amino acids, for example. However, these are introduced in a manner distinct from that employed to synthesize proteins. 

Natural product HDAC inhibitor Helminthosporium carbonum (HC)-toxin (Fig. 14) is produced from filamentous fungus Cochliobolus carbonum Like chlamydocin, this compound is a cyclic peptide that contains both D- and L-amino acids to relieve ring strain. The epoxy group... 

There is a correlation between d- and L-glyceraldehyde and D- and L-amino acids, in that it is possible to convert one system chemically into another without affecting... 

There are two major approaches to achieve enantiomeric separation of d- and L-amino acids. The first involves precolumn derivatization with a chiral reagent, followed by RP-HPLC [226], while the second involves direct separation of underivatized enantiomers on a chiral bonded phase [227], Weiss et al. [209] determined d- and L-form of amino acids by applying derivatization with OPA and chiral /V-isobutyryl-L-cysteine. 

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