The crystal structure of Z‐(Aib)10‐OH at 0.65 Å resolution: three complete turns of 310‐helix

The synthetic peptide Z‐(Aib)₁₀‐OH was crystallized from hot methanol by slow evaporation. The crystal used for data collection reflected synchrotron radiation to sub‐atomic resolution, where the bonding electron density becomes visible between the non‐hydrogen atoms. Crystals belong to the centrosymmetric space group P . Both molecules in the asymmetric unit form regular 3₁₀‐helices. All residues in each molecule possess the same handedness, which is in contrast to all other crystal structure determined to date of longer Aib‐homopeptides. These other peptides are C‐terminal protected by OtBu or OMe. In these cases, because of the missing ability of the C‐terminal protection group to form a hydrogen bond to the residue i‐3, the sense of the helix is reversed in the last residue. Here, the C‐terminal OH‐groups form hydrogen bonds to the residues i‐3, in part mediated by water molecules. This makes Z‐(Aib)₁₀‐OH an Aib‐homopeptide with three complete 3₁₀‐helical turns in spite of the shorter length it has compared with Z‐(Aib)₁₁‐OtBu, the only homopeptide to date with three complete turns.     

Identification and Biological Activities of Long‐Chain Peptaibols Produced by a Marine‐Derived Strain of Trichoderma longibrachiatum

Six long‐chain peptaibols, 1  –  6 , were identified from agar cultures of a marine‐derived Trichoderma longibrachiatum Rifai strain (MMS151) isolated from blue mussels. The structure elucidation was carried out using electrospray ionization ion trap mass spectrometry (ESI‐IT‐MS) and GC/EI‐MS. The long‐chain peptaibols exhibited the general building scheme Ac‐Aib‐Ala‐Aib‐Ala‐Aib‐XXX‐Gln‐Aib‐Vxx‐Aib‐Gly‐XXX‐Aib‐Pro‐Vxx‐Aib‐XXX‐Gln‐Gln‐Pheol and were similar or identical to recurrent 20‐residue peptaibols produced by Trichoderma spp. Three new sequences were identified and were called longibrachins A‐0, A‐II‐a, and A‐IV‐b. The isolated peptaibols were assayed for cytotoxic, antibacterial, and antifungal activities, and acute toxicity on Dipteran larvae.     

Characterization of a type of β‐bend ribbon spiral generated by the repeating (Xaa–Yaa–Aib–Pro) motif: The solution structure of harzianin HC IX,a 14‐residue peptaibol forming voltage‐dependent ion channels

The three‐dimensional solution structure of harzianin HC IX, a peptaibol antibiotic isolated from the fungus Trichoderma harzianum, was determined using CD, homonuclear, and heteronuclear two‐dimensional nmr spectroscopy combined with molecular modeling. This 14‐residue peptide, Ac Aib¹ Asn² Leu³ Aib⁴ Pro⁵ Ala⁶ Ile⁷ Aib⁸ Pro⁹ Iva¹⁰ Leu¹¹ Aib¹² Pro¹³ Leuol¹⁴ (Aib, α‐aminoisobutyric acid; Iva, isovaline; Leuol, leucinol), is a main representative of a short‐sequence peptaibol class characterized by an acetylated N‐terminus, a C‐terminal amino alcohol, and the presence of three Aib‐L ‐Pro motifs at positions 4–5, 8–9, and 12–13, separated by two dipeptide units. In spite of a lower number of residues, compared to the 18/20‐residue peptaibols such as alamethicin, harzianin HC IX exhibits remarkable membrane‐perturbing properties. It interacts with phospholipid bilayers, increasing their permeability and forming voltage‐gated ion channels through a mechanism slightly differing from that proposed for alamethicin. Sequence‐specific ¹H‐ and ¹³C‐nmr assignments and conformational nmr parameters (³J_NHCαH coupling constants, quantitative nuclear Overhauser enhancement data, temperature coefficients of amide and carbonyl groups, NH–ND exchange rates) were obtained in methanol solution. Sixty structures were calculated based on 98 interproton distance restraints and 6 Φ dihedral angle restraints, using high temperature restrained molecular dynamics and energy minimization. Thirty‐seven out of the sixty generated structures were consistent with the nmr data and were convergent. The peptide backbone consists in a ribbon of overlapping β‐turns twisted into a continuous spiral from Asn² to Leuol¹⁴ and forming a 26 Å long helix‐like structure. This structure is slightly amphipathic, with the three Aib–Pro motifs aligned on the less hydrophobic face of the spiral where the Asn² side chain is also present, while the more hydrophobic bulky side chains of leucines, isoleucine, isovaline, and leucinol are located on the concave side. The repetitive (Xaa–Yaa–Aib–Pro) tetrapeptide subunit, making up the peptide sequence, is characterized by four sets of (Φ,Ψ) torsional angles, with the following mean values: Φ_i = −90°, Ψ_i = −27°; Φ_i+1 = −98°, Ψ_i+1 = −17°; Φ_i+2 = −49°, Ψ_i+2 = −50°; Φ_i+3 = −78°, Ψ_i+3 = +3°. We term this particular structure, specifically occurring in the case of (Xaa–Yaa–Aib–Pro)_n sequences, the (Xaa–Yaa–Aib–Pro)‐β‐bend ribbon spiral. It is stabilized by 4 → 1 intramolecular hydrogen bonds and differs from both the canonical 3₁₀‐helix made of a succession of type III β‐turns and from the β‐bend ribbon spiral that has been described in the case of (Aib–Pro)n peptide segments. © 1999 John Wiley & Sons, Inc. Biopoly 50: 71–85, 1999     

Solution phase synthesis of the 14-residue peptaibol antibiotic trichovirin I

Summary.  The 14-residue peptaibol antibiotic trichovirin I 4A of the structure Ac-Aib-L-Asn-L-Leu-Aib-L-Pro-L-Ala-L-Val-Aib-L-Pro-Aib-L-Leu-Aib-L-Pro-L-Leuol (Aib = α-aminoisobutyric acid, Leuol = leucinol) was synthesized by stepwise conventional solution phase synthesis using the Z/OtBu(OMe) strategy and HOBt/EDC as coupling reagents. Intermediates were fully characterized and the identity of the synthetic peptide with the component 4A of the natural, microheterogeneous peptide mixture was proven by electrospray mass spectrometry, HPLC, and bioassay. Received March 25, 2002 Accepted June 14, 2002 Published online December 18, 2002 RID="*" ID="*"  Dedicated to Prof. Dr. Günther Jung. Tübingen University, on the occasion of his 65^th anniversary. Authors' address: Prof. Dr. Hans Brückner, Interdisciplinary Research Center, Institute of Nutritional Science, Department of Food Sciences, Justus-Liebig-University of Giessen, Heinrich-Buff-Ring 26, D-35392 Giessen, Germany, Fax: +49-641-99-39149, E-mail: hans.brueckner@ernaehrung.uni-giessen.de Abbreviations: Amino acids are abbreviated according to three-letter-nomenclature; Aib, α-aminoisobutyric acid (2-methylalanine); Iva (isovaline, 2-ethylalanine); Leuol, L-leucinol [(S)-2-amino-4-methyl-1-pentanol]; AAA, amino acid analysis; EI-MS, electron impact mass spectrometry; ESI-MS, electrospray ionization mass spectrometry; HPLC, high performance liquid chromatography; Z, benzyloxycarbonyl; Fmoc, 9-fluorenylmethyoxycarbonyl; OtBu, tertiary butoxy (tert-butylester); OMe, methoxy (methyl ester); OBzl, benzyloxy (benzyl ester); TDM, N,N,N′,N′-tetramethyl-4,4′-diamino-diphenylmethane (Arnold's base); for other abbreviations see Experimental.     

Conformations of helical Aib peptides containing a pair of l‐amino acid and d‐amino acid

A pair of l ‐leucine (l ‐Leu) and d ‐leucine (d ‐Leu) was incorporated into α‐aminoisobutyric acid (Aib) peptide segments. The dominant conformations of four hexapeptides, Boc‐l ‐Leu‐Aib‐Aib‐Aib‐Aib‐l ‐Leu‐OMe (1a), Boc‐d ‐Leu‐Aib‐Aib‐Aib‐Aib‐l ‐Leu‐OMe (1b), Boc‐Aib‐Aib‐l ‐Leu‐l ‐Leu‐Aib‐Aib‐OMe (2a), and Boc‐Aib‐Aib‐d ‐Leu‐l ‐Leu‐Aib‐Aib‐OMe (2b), were investigated by IR, ¹H NMR, CD spectra, and X‐ray crystallographic analysis. All peptides 1a,b and 2a,b formed 3₁₀‐helical structures in solution. X‐ray crystallographic analysis revealed that right‐handed (P) 3₁₀‐helices were present in 1a and 1b and a mixture of right‐handed (P) and left‐handed (M) 3₁₀‐helices was present in 2b in their crystalline states. Copyright © 2012 European Peptide Society and John Wiley & Sons, Ltd.     

Conformations of peptides containing a chiral cyclic α, α‐disubstituted α‐amino acid within the sequence of Aib residues

A single chiral cyclic α,α‐disubstituted amino acid, (3S,4S)‐1‐amino‐(3,4‐dimethoxy)cyclopentanecarboxylic acid [(S,S)‐Ac₅c^dOM], was placed at the N‐terminal or C‐terminal positions of achiral α‐aminoisobutyric acid (Aib) peptide segments. The IR and ¹H NMR spectra indicated that the dominant conformations of two peptides Cbz‐[(S,S)‐Ac₅c^dOM]‐(Aib)₄‐OEt ( 1) and Cbz‐(Aib)₄‐[(S,S)‐Ac₅c^dOM]‐OMe (2) in solution were helical structures. X‐ray crystallographic analysis of 1 and 2 revealed that a left‐handed (M) 3₁₀‐helical structure was present in 1 and that a right‐handed (P) 3₁₀‐helical structure was present in 2 in their crystalline states. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.     

Controlling the helical screw sense of peptides with C‐terminal L‐valine

One chiral L ‐valine (L ‐Val) was inserted into the C‐terminal position of achiral peptide segments constructed from α‐aminoisobutyric acid (Aib) and α,β‐dehydrophenylalanine (Δ^ZPhe) residues. The IR, ¹H NMR and CD spectra indicated that the dominant conformations of the pentapeptide Boc‐Aib‐ΔPhe‐(Aib)₂‐L ‐Val‐NH‐Bn (3) and the hexapeptide Boc‐Aib‐ΔPhe‐(Aib)₃‐L ‐Val‐NH‐Bn (4) in solution were both right‐handed (P) 3₁₀‐helical structures. X‐ray crystallographic analyses of 3 and 4 revealed that only a right‐handed (P) 3₁₀‐helical structure was present in their crystalline states. The conformation of 4 was also studied by molecular‐mechanics calculations. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.     

Peptide–peptoid hybrids based on (1–11)‐parathyroid hormone analogs

A series of peptide–peptoid hybrids, containing N‐substituted glycines, were synthesized based on the H‐Aib‐Val‐Aib‐Glu‐Ile‐Gln‐Leu‐Nle‐His‐Gln‐Har‐NH₂ (Har = Homoarginine) as the parent parathyroid hormone (1–11) analog. The compounds were pharmacologically characterized in their agonistic activity at the parathyroid hormone 1 receptor. Copyright © 2010 European Peptide Society and John Wiley & Sons, Ltd.     

Determination of puerarin in biological samples and its application to a pharmacokinetic study by flow‐injection chemiluminescence

A simple and sensitive flow injection–chemiluminescence (FI–CL) method has been developed for the determination of puerarin, based on the fact that puerarin can greatly inhibit CL of the luminol–H₂O₂–haemoglobin system. The inhibition of CL intensity was linear to the logarithm of the concentration of puerarin in the range 0.08–10.0 μg/mL (r² = 0.9912). The limit of detection was 0.05 μg/mL (3σ) and the relative standard deviation (RSD) for 1.0 μg/mL (n = 11) of puerarin solution was 1.4%. Coupled with solid‐phase extraction (SPE) as the sample pretreatment, the determination of puerarin in biological samples and a preliminary pharmocokinetic study of puerarin in rats were performed. The recoveries for plasma and urine at three different concentrations were 89.2–110.0% and 91.4–104.8%, respectively. The pharmacokinetics of puerarin in plasma of rat coincides with the two‐compartment open model. The T_1/2α, T_1/2β, CL/F, V_Z/F, AUC_{(0 – t)}, MRT_{(0 – ∞)}, T_max and C_max were 0.77 ± 0.21 h, 7.55 ± 2.64 h, 2.43 ± 1.02 L/kg/h, 11.40 ± 3.45 L/kg, 56.67 ± 10.65 mg/h/L, 5.04 ± 2.78 h, 1.00 ± 0.35 h and 19.70 ± 4.67 μg/mL, respectively. Copyright © 2011 John Wiley & Sons, Ltd.     

Heterotrimeric collagen peptides containing functional epitopes. Synthesis of single‐stranded collagen type I peptides related to the collagenase cleavage site

Synthetic collagen peptides containing larger numbers of Gly‐Pro‐Hyp repeats are difficult to purify by standard chromatographic procedures. Therefore, efficient strategies are required for the synthesis of higher molecular weight collagen‐type peptides. Applying the Fmoc/tBu chemistry, a comparative analysis of the standard stepwise chain elongation procedure on solid support with the procedure based on the use of the synthons Fmoc‐Gly‐Pro‐Hyp(tBu)‐OH and Fmoc‐Pro‐Hyp‐Gly‐OH was performed. The crude products resulting from the stepwise elongation procedure and from the use of Fmoc‐Gly‐Pro‐Hyp(tBu)‐OH clearly revealed large amounts of microheterogeneities that result from incomplete imino acid acylation as well as from diketopiperazine formation with cleavage of Gly‐Pro units from the growing peptide chain. Conversely, by the use of the Fmoc‐Pro‐Hyp‐Gly‐OH synthon, the quality of the crude products was significantly improved; moreover, protection of the Hyp side chain hydroxyl function is not required using the Fmoc/tBu strategy. With this optimized synthetic procedure, relatively large collagen‐type peptides were obtained in satisfactory yields as highly homogeneous compounds. Copyright © 1999 European Peptide Society and John Wiley & Sons, Ltd.     

Use ofα-aminoisobutyric acid and isovaline as marker amino acids for the detection of fungal polypeptide antibiotics. Screening ofHypocrea

Summary Filamentous fungi of the genusHypocrea were grown on malt extract/peptone agar, the mycelia were extracted with dichloromethane/methanol, and the extracts were totally hydrolyzed with 6 N HCl (110°C, 24 h). The amino acids (AA) released from peptides were converted into theirN(O)-pen-tafluoropropionyl 1-propyl esters and investigated by gas chromatography and gas chromatography/mass spectrometry for the presence of the nonprotein AA-aminoisobutyric acid (Aib) and its homologue isovaline (Iva). In particular Aib served as specific marker compound for a particular group of fungal peptides named peptaibiotics,i.e. peptides containing Aib and having antibiotic activities. Screening of 24 species ofHypocrea revealed that the majority was capable of producing peptaibiotics. The reliability of the screening procedure was shown with the isolation of peptaibiotics fromHypocrea muroiana andHypocrea nigricans. These findings extend the list of genera of fungi already known to produce Aib-containing peptides and also establish that Aib and Iva are fairly common in the biosphere.     

A new quaternary photoluminescence enhancement system of Eu−N‐(o‐vanillin)‐1,8‐diaminonaphthalene−1,10‐phenanthroline−Zn and its application in determining trace amounts of europium and zinc

A new sensitive quaternary photoluminescence enhancement system has been successfully developed to determine trace amounts of Eu³⁺ and Zn²⁺. The photoluminescence intensity of Eu ? N‐(o‐vanilin)‐1,8‐diaminonaphthalene systems was greatly increased by the addition of specific concentrations of 1, 10‐phenanthroline and Zn²⁺. The excitation and emission wavelengths were 274 and 617 nm, respectively. Under optimal system conditions, the photoluminescence intensity showed a linear response toward Eu³⁺ in the range of 5.0 × 10^–6 ~ 2.0 × 10^–5 M with a limit of detection (= 2.2 × 10^–9 M) and the photoluminescence intensity of the system decreased linearly by increasing the Zn²⁺ concentration in the range of 5.0 × 10^–8 ~ 1.0 × 10^–6 M with a limit of detection (= 8.8 × 10^–11 M). This system was successfully applied for the determination of trace amounts of Eu³⁺ in a high purity La₂O₃ matrix and in the synthetic rare earth oxide mixture, and of Zn²⁺ in a high purity Mg(NO₃)₂ · 6H₂O matrix and in synthetic coexisting ionic matrixes. The energy transfer mechanism, photoluminescence enhancement of the system and interference of other lanthanide ions and common coexisting ions were also studied in detail. Copyright © 2013 John Wiley & Sons, Ltd.     

Nα-Fmoc-O,O-(dimethylphospho)-L-tyrosine fluoride: A convenient building block for the solid-phase synthesis of phosphotyrosyl peptides

Summary Fmoc-O,O-(dimethylphospho)-l-tyrosine was converted into stable Fmoc-O,O-(dimethylphospho)-L-tyrosine fluoride by means of (diethylamino) sulfur trifluoride or cyanuric fluoride. This building block was used for efficient coupling of phosphotyrosine to the adjacent sterically hindered amino acid Aib or Ac₆c in, model peptide sequences as well as for the synthesis of the ‘difficult’ phosphotyrosine peptide Stat91^695–708. The phosphate methyl groups were cleaved on solid phase after peptide assembly by means of trimethylsilyl iodide in MeCN. Aib, α-aminoisobutyric acid Ac₆c, 1-amino-cyclohexyl-l-carboxylic acid; BOP, benzotriazol-l-yl-oxy-tris(dimethylamino) phosphonium hexafluorophosphate, CIP, 2-chloro-l, 3-dimethylimidazolidium hexafluorophosphate, DAST, (diethylamino)sulfur trifluoride; DBU 1,8-diazabicyclo[5.4.0]undec-7-ene; DCM, dichloromethane; DIEA, drisopropylethylamine; DMA dimethylacetamide; Fmoc, 9-fluorenylmethoxycarbonyl; HATU,O-(7-azabenzotriazol-l-yl)-1.1,3,3-tetramethyluronium hexafluorophosphate; HOAt, I-hydroxy-7-azabenzotriazole; HOBt,N-hydroxybenzotriazole; HPLC, high-performance liquid chromatography; MBHA, 4-methylbenzhydrylamine; MeCN, acetonitrile; NMP,N-methyl-2-pyrrolidinone; NMR, nuerear magnetic resonance; PS, polystyrene; PyBroP, bromotris(pyrrolidino)phosphonium hexafluorophosphate; Rink amide MBHA-PS, 4-(2′,4′-dimethoxyphenyl-Fmoc-aminophenyl)-phenoxyacetamido-norleucyl-MBHA-PS; TFA, trifluoroacetic acid; TMSI, trimethylsilyl iodide; TPTU, 2-(2-pyridon-l-yl)-1,1,3,3-tetramethyluroniumfluoroborate; t_R, retention time; UNCA, arethane-protected amino acidN-carboxy anhydride Abbreviations for amino acids and nomenclature of, peptide structures follow the recommendations of the IUPAC-IUB Commission on Biochemical Nomenclature [Eur. J. Biochem., 138 (1984) 9].     

The crystal state conformation of Aib-rich segments of peptaibol antibiotics

Ac-(Aib-Ala)₃-OH (a protected segment of the peptaibols gliodeliquescin and paracelsin), Z-Leu-Aib-Val-Aib-Gly-OtBu (a segment of [Leu]⁷-gliodeliquescin), Z-Val-Aib-Aib-Gln-OtBu (a common segment of alamethicin, paracelsin, and hypelcin), and Ac-Aib-Pro-(Aib-Ala)₂-OMe and Z-Aib-Pro-(Aib-Ala)₂-OMe, which represent differently N^α-protected 1–6 segments of alamethicin and hypelcin, have been synthesized by solution methods. The crystal-state conformations of these five Aib-containing peptides have been determined by X-ray diffraction analysis. We have confirmed that the 3₁₀-helical structure is preferentially adopted by Aib-rich short peptides. An experimentally unambiguous proof for the 3₁₀→α-helix conversion has been provided by the two differently N-blocked -Aib-Pro-(Aib-Ala)₂-OMe hexapeptides. The β-bend ribbon conformation, commonly observed in the (Aib-Pro)_n sequential oligopeptides, is not found in the -Aib-Pro-Aib-Ala-Aib-Ala- sequence. As expected on the basis of the l -configuration of the C^α-monoalkylated residues, a right-handed helix screw sense was found in all peptides investigated. © 1998 European Peptide Society and John Wiley & Sons, Ltd.     

Terminal effect of chiral residue on helical screw sense in achiral peptides

To understand the terminal effect of chiral residue for determining a helical screw sense, we adopted five kinds of peptides I – V containing N‐ and/or C‐terminal chiral Leu residue(s): Boc–L ‐Leu–(Aib–ΔPhe)₂–Aib–OMe ( I ), Boc–(Aib–ΔPhe)₂–L ‐Leu–OMe ( II ), Boc–L ‐Leu–(Aib–ΔPhe)₂–L ‐Leu–OMe ( III ), Boc–D ‐Leu–(Aib–ΔPhe)₂–L ‐Leu–OMe ( IV ), and Boc–D ‐Leu–(Aib–ΔPhe)₂–Aib–OMe ( V ). The segment –(Aib–ΔPhe)₂– was used for a backbone composed of two “enantiomeric” (left‐/right‐handed) helices. Actually, this could be confirmed by ¹H‐nmr [nuclear Overhauser effect (NOE) and solvent accessibility of NH resonances] and CD spectroscopy on Boc–(Aib–ΔPhe)₂–Aib–OMe, which took a left‐/right‐handed 3₁₀‐helix. Peptides I – V were also found to take 3₁₀‐type helical conformations in CDCl₃, from difference NOE measurement and solvent accessibility of NH resonances. Chloroform, acetonitrile, methanol, and tetrahydrofuran were used for CD measurement. The CD spectra of peptides I – III in all solvents showed marked exciton couplets with a positive peak at longer wavelengths, indicating that their main chains prefer a left‐handed screw sense over a right‐handed one. Peptide V in all solvents showed exciton couplets with a negative peak at longer wavelengths, indicating it prefers a right‐handed screw sense. Peptide IV in chloroform showed a nonsplit type CD pattern having only a small negative signal around 280 nm, meaning that left‐ and right‐handed helices should exist with almost the same content. In the other solvents, peptide IV showed exciton couplets with a negative peak at longer wavelengths, corresponding to a right‐handed screw sense. From conformational energy calculation and the above ¹H‐nmr studies, an N‐ or C‐terminal L ‐Leu residue in the lowest energy left‐handed 3₁₀‐helical conformation was found to take an irregular conformation that deviates from a left‐handed helix. The positional effect of the L ‐residue on helical screw sense was discussed based on CD data of peptides I – V and of Boc–(L ‐Leu–ΔPhe)_n–L ‐Leu–OMe (n = 2 and 3). © 1999 John Wiley & Sons, Inc. Biopoly 49: 551–564, 1999     

Influence of pH and micellar systems on the sensitized photo‐oxidation of bovine serum albumin

Photosensitized oxidation of bovine serum albumin (BSA), by using perinaphtenone as a sensitizer, has been studied at pH 7.4 and 11. The selected sensitizer does not present ground‐state complexation with BSA and ensures that the mechanism is mediated by O₂(¹△_g). Strong dependence between BSA–O₂(¹△_g) photo‐oxidation and the pH of the medium has been found. The relative oxygen uptake rate (v_? △ O2 ) and the total quenching rate constant (k_t) values are higher at pH 11 than pH 7.4. The enhancement in the alkaline condition is due to conformational changes in the protein and the reactivity of tyrosinate anion with O₂(¹△_g). Even when the tendency with the pH in the presence of sodium dodecyl sulfate (SDS) micelles is similar to that observed in homogeneous media, an increment on the k_t value is detected. This effect may be attributable to the strong interaction of BSA–SDS, which leads to the protein unfolding and could leave more exposed photo‐oxidizable amino acids. A protective effect against the O₂(¹△_g)‐mediated photo‐oxidation was observed in reverse micelles (RMs) of sodium bis(2‐ethylhexyl)sulfosuccinate (AOT) by comparing the k_t values obtained at W = 10 with respect to the one obtain in homogeneous media. The latter could be mainly explained by the modification in the solvent polarity. Also, another important observation was found, the internal pH inside RMs of AOT sensed through tyrosine absorption was independent of the one used for the formation of the water pool. Hence, the k_t values observed at both pH, are quite similar.     

Synthesis and Solid State Conformation of Tetrapeptide Amides Containing two Aib and two (αMe)Phe Residues – Use of Enantiomerically Pure 2‐Benzyl‐2‐methyl‐2H‐azirin‐3‐amines as (αMe)Phe‐Synthons

A series of tetrapeptide amides containing two aminoisobutyric acids (Aib) and two α‐methylphenylalanine ((αMe)Phe) units were prepared through the ‘azirine/oxazolone method’. New 2‐benzyl‐2‐methyl‐2H‐azirin‐3‐amines have been used for the selective introduction of (S)‐ and (R)‐(αMe)Phe, respectively. The solid‐state conformations of five tetrapeptide amides were determined by X‐ray crystallography. In all cases, two β‐turns stabilize 3₁₀‐helical conformations and it was confirmed that, in contrast to proteinogenic amino acids, the configuration of (αMe)Phe does not determine the screw sense of the helix.     

Effect of one D‐Leu residue on right‐handed helical ‐L‐Leu‐Aib‐ peptides in the crystal state

Four diastereomeric‐Leu‐Leu‐Aib‐Leu‐Leu‐Aib‐peptides, Boc‐D ‐Leu‐L ‐Leu‐Aib‐L ‐Leu‐L ‐Leu‐Aib‐OMe (1), Boc‐L ‐Leu‐D ‐Leu‐Aib‐L ‐Leu‐L ‐Leu‐Aib‐OMe (2), Boc‐L ‐Leu‐L ‐Leu‐Aib‐D ‐Leu‐L ‐Leu‐Aib‐OMe (3), and Boc‐L ‐Leu‐L ‐Leu‐Aib‐L ‐Leu‐D ‐Leu‐Aib‐OMe (4), were synthesized. The crystals of the four hexapeptides were characterized by X‐ray crystallographic analysis. Two diastereomeric hexapeptides 1 and 2 having D ‐Leu(1) or D ‐Leu(2) were folded into right‐handed (P) 3 ₁₀ ‐helical structures, while peptide 3 having D ‐Leu(4) was folded into a turn structure nucleated by type III′ and I$' \bf{\beta}$ ‐turns, and peptide 4 having D ‐Leu(5) was folded into a left‐handed (M) 3 ₁₀ ‐helical structure. Copyright © 2011 European Peptide Society and John Wiley & Sons, Ltd.     

Scavenging of superoxide anion radical and hydroxyl radical by novel thiazolyl‐thiazolidine‐2,4‐dione compounds

The antioxidant behavior of a series of new synthesized substituted thiazolyl‐thiazolidine‐2,4‐dione compounds (TZDs) was examined using chemiluminescence and electron paramagnetic resonance spin trapping techniques. 5,5‐Dimethyl‐1‐pyrroline‐N‐oxide (DMPO) was used as the spin trap. The reactivity of TZDs with superoxide anion radical (O) and hydroxyl radical (HO^?) was evaluated using potassium superoxide/18‐crown‐6 ether dissolved in dimethylsulfoxide, and the Fenton‐like reaction (Fe²⁺ + H₂O₂), respectively. The results showed that TZDs efficiently inhibited light emission from the O generating system at a concentration of 0.05–1 mmol L^?1 (5–94% reductions were found at 1 mmol L^?1 concentration). The TZD compounds showed inhibition of HO^?‐dependent DMPO–OH spin adduct formation from DMPO (the amplitude decrease ranged from 8 to 82% at 1 mmol L^?1 concentration). The findings showed that examined TZDs had effective activities as radical scavengers. Copyright © 2009 John Wiley & Sons, Ltd.     

An efficient method for the synthesis of phenacyl ester‐protected dipeptides using neutral alumina‐supported sodium carbonate ‘Na2CO3/n‐Al2O3’

In the synthesis of dipeptides (Boc‐AA¹‐AA²‐OPac: AA¹ and AA² represent amino acids) protected by phenacyl (Pac) ester, amines and solid bases as the base for the conversion of the trifluoroacetic acid (TFA) salt of the amino component (TFA·H‐AA²‐OPac) into the corresponding free amino component (H‐AA²‐OPac) were examined. The synthesis of a dipeptide (Boc‐Ala‐Gly‐OPac) using amines for the conversion afforded an unsatisfactory yield with by‐products. On the other hand, the use of neutral alumina‐supported Na₂CO₃ (Na₂CO₃/n‐Al₂O₃) as a solid base for the conversion provided the dipeptide in a quantitative yield without by‐products. The application of Na₂CO₃/n‐Al₂O₃ to the synthesis of some dipeptides protected by Pac ester gave the desired peptides in excellent yields. Copyright © 2013 European Peptide Society and John Wiley & Sons, Ltd.