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1.
Efficient syntheses of 4-(R,S-hydroxyphosphonomethyl)-l -phenylalanine and 4-carboxy-l -phenylalanine within the context of the pentapeptide Ac-Ile-X-Gly-Glu-Phe-NH2 (wherein X = the unnatural amino acid) illustrate the use of a divergent synthetic strategy from an advanced common peptide intermediate to more readily access peptide-based tyrosine kinase inhibitors. The key intermediate, Ac-Ile-Phe(4-formyl)-Gly-Glu(O-tBu)-Phe-NH2, was synthesized by a facile palladium-catalyzed carbonylation of Ac-Ile-Phe(4-iodo)-Gly-Glu(O-tBu)-Phe-NH2. Oxidation of Ac-Ile-Phe(4-formyl)-Gly-Glu(O-tBu)-Phe-NH2 with tetrabutylammonium permanganate or addition of di-t-butylphosphite, both followed by trifluoroacetic acid deprotection, gave the target pentapeptide inhibitors wherein X = 4-carboxy-l -phenylalanine or 4-(R,S-hydroxyphosphonomethyl)-l -phenylalanine, respectively. These two peptides gave somewhat more potent inhibition of the tyrosine kinase pp60c-src than the corresponding pentapeptide wherein X =l -phenylalanine, demonstrating that appended functionalities at the 4-position are accepted and can enhance binding through added interactions within the catalytic region of the active site.  相似文献   

2.
Cyclic peptide structures of the type -Lys-R1—Rn-Glu- can be synthesized on the Merrifield resin by assembling the peptide chain using Nα-Fmoc-amino acids and Boc and tert.-butyl protection for the side-chains of Lys and Glu, respectively. If residues R1 to Rn contain side-chain functional groups, TFA-resistant protection is required. After TFA treatment cyclization on the resin can be performed with appropriate coupling reagents. The formation of such cyclic structures may be preceded or followed by peptide chain assembly using Nα-Boc-amino acids and the entire peptide chain containing the cyclic portion is finally cleaved by HF treatment. Using this principle we synthesized the following opioid peptide related cyclic analogs: H-Tyr-d -Lys-Gly-Phe-Glu-NH2 (I), H-Tyr-Lys-Gly-Phe-Glu-NH2 (II), H-Tyr-d -Lys-Phe-Glu-NH2 (III), H-Tyr-d -Glu-Gly-Phe-Lys-NH2 (IV), H-Tyr-d -Glu-Phe-Lys-NH2 (V), H-Tyr-d -Orn-Gly-Glu-NH2 (VI) and H-Tyr-d -Ala-Lys-Phe-Glu-NH2 (VII). Cyclic monomers were obtained in all cases, as demonstrated by mass spectrometry. Analysis of side-products revealed a slow-down of the HF deprotection of O-benzylated tyrosine as a consequence of hydrophobic interactions as well as the formation of a side-chain-linked antiparallel cyclic dimer in the case of compound VI. In conclusion, the described method permits the convenient preparation of peptide analogs cyclized via amide bond formation between side-chain amino and carboxyl groups in reasonable yield.  相似文献   

3.
Purpose. To elucidate the major degradation products of the metal-catalyzedoxidation of (cyclo S-S) AcCys-Ala-X-Val-Gly-CysNH2(X = His, cyclic-His peptide), which is a fragment of the proteinrelaxin, and the effect of this oxidation on its solution structure. Methods. The cyclic-His peptide and its potential oxidative degradationproducts, cyclic-Asp peptide (X = Asp) and cyclic-Asn peptide(X = Asn), were prepared by using solid phase peptide synthesisand purified by preparative HPLC. The degradation of the cyclic-Hispeptide was investigated at pH 5.3 and 7.4 in an ascorbate/cupricchloride/oxygen [ascorbate/Cu(II)/O2] system in the absence or presenceof catalase (CAT), superoxide dismutase (SOD), isopropanol, andthiourea. The oxidation of the cyclic-His peptide was also studied in thepresence of hydrogen peroxide (H2O2). All reactions were monitored byreversed-phase HPLC. The main degradation product of the cyclic-Hispeptide formed at pH 7.4 in the presence of ascorbate/Cu(II)/O2was isolated by preparative HPLC and identified by 1H NMR andelectrospray mass spectrometry. The complexation of Cu(II) with thecyclic-His peptide was determined with 1H NMR. The solution structureof the cyclic-His peptide in the presence and absence of Cu(II) at pH5.3 and 7.4 and the solution structure of the main degradation productwere determined using circular dichroism (CD). Results. CAT and thiourea were effective in stabilizing the cyclic-Hispeptide to oxidation by ascorbate/Cu(II)/O2, while SOD and isopropanolwere ineffective. Cyclic-Asp and cyclic-Asn peptides were notobserved as degradation products of the cyclic-His peptide oxidized atpH 5.3 and 7.4 in an ascorbate/Cu(II)/O2 system. The main degradationproduct formed at pH 7.4 was the cyclic 2-oxo-His peptide (X = 2-oxo-His).At pH 5.3, numerous degradation products were formed inlow yields, including the cyclic 2-oxo-His peptide. The cyclic 2-oxo-Hispeptide appeared to have a different secondary structure than didthe cyclic-His peptide as determined by CD. 1H NMR results indicatecomplexation between the cyclic-His peptide and Cu(II). CD resultsindicated that the solution structure of the cyclic-His peptide in thepresence of Cu(II) at pH 5.3 was different than the solution structureobserved at pH 7.4. Conclusions. H2O2 and superoxide anion radical ( ) were deducedto be the intermediates involved in the ascorbate/Cu(II)/O2-inducedoxidation of cyclic-His peptide. H2O2 degradation by a Fenton-typereaction appears to form secondary reactive-oxygen species (i.e.,hydroxyl radical generated within complex forms or metal-bound formsof hydroxyl radical) that react with the peptide before they diffuse intothe bulk solution. CD results indicate that different complexes areformed between the cyclic-His peptide and Cu(II) at pH 5.3 and pH7.4. These different complexes may favor the formation of differentdegradation products. The apparent structural differences between thecyclic-His peptide and the cyclic 2-oxo-His peptide indicate that conformationof the cyclic-His peptide was impacted by metal-catalyzedoxidation.  相似文献   

4.
The peptide Boc-Ser-Phe-OCH3 was synthesised by a solution-phase method using the usual workup procedure. The peptide was crystallized from a 70:30 (v/v) methanol-water mixture. The crystals are monoclinic, space group P21 with a= 5.128(2), b=17.873(2), c=11.386(2) Å, and β=98.03(3)°. The structure was determined by direct methods and refined by a structure factor least-squares procedure. The final R-value for 1499 observed reflections was 0.041. The structure contains one peptide and one solvent water molecule. The peptide adopts a β-strand-like conformation with φ1=- 100.3(5), ψl= 99.9(5), φ2= - 122.2(5), ψT2= -172.5(6)°. The Ser side-chain assumes an extended conformation with χ11= - 177.0(4)°. The OγH group of serine acts as a proton donor in an intramolecular weak hydrogen bond with (Ser) O′1; [Oγ1;-Hγ1?O′1= 3.253(6) Å]. The Phe side-chain adopts a staggered conformation with χ12= -70.9(6), χ22,1= 88.4(7)°, χ2,22= -89.2(6)°. The water molecule generates a loop through two hydrogen bonds with Oγ1 [OW?Oγ1= 2.893(5) Å] and O′2 [OW-O′2= 2.962(7) Å] atoms. The unit-translated peptide molecules along the α-axis are held by hydrogen bonds: N1-H1?O2 (x-1, y, z) = 2.954(4) Å and N2-H2?O′1 (x+1, y, z) = 2.897(6) Å in a manner similar to those observed in parallel β-pleated sheet structures. There is an additional interaction involving Oγ1 and the water molecule [OW?Oγ1 (x= 1, y, z) = 2.789(4) Å]. The strong NOE peak of Ci(H)?Ni+1 (H) and a simultaneous weak NOE peak of Ni(H)?Ni+l (H) in the ROESY spectra of two-dimensional NMR in dimethyl sulfoxide indicate a β-strand-like conformation for the peptide in solution. © Munksgaard 1996.  相似文献   

5.
A general method for the synthesis of O-phosphonotyrosyl peptides using solid phase methodology is described. Protected O-phosphonotyrosine derivatives with the general structure Boc-Tyr(R2PO3)-OH (R = methyl, ethyl or benzyl) were prepared as potential synthons for the introduction of O-phosphonotyrosine residues into peptide sequences. Using 31P n.m.r. spectroscopy, the alkyl phosphate protecting groups (R = methyl or ethyl) were shown to be stable to the coupling, deprotection and neutralization cycles of the Merrifield method of solid phase peptide synthesis. Facile removal of the methyl phosphate protecting groups from the O-phosphonotyrosyl peptide analogue Ac-Tyr(Me2PO3)-NHMe was demonstrated using 45% HBr/acetic acid. The O-phosphonotyrosyl heptapeptide H-Leu-Arg-Arg-Ala-PTyr-Leu-Gly-OH was subsequently prepared using solid phase methodology via incorporation of N2-tert-butyloxycarbonyl-O-dimethylphosphonotyrosine.  相似文献   

6.
Using a random combinatorial peptide library method [Wu, J., Ma, Q. N. & Lam, K. S. (1994) Biochemistry 33 , 14825–14833] a novel peptide, YIYGSFK, was identified as a substrate for p60c-src protein tyrosine kinase. Mass spectrometric analysis showed that tyrosine-3 from the N-terminus was the phosphorylation site. Kinetic studies showed that the Km of YIYGSFK for p60c-src was 55 μM, about 6.4-fold lower than a peptide derived from p34cdc2 [cdc2(6–20), KVEKIGEGTYGVVYK], which had been reported to be a specific and efficient substrate for the Src-family protein tyrosine kinases. Comparison of the specificity of YIYGSFK and cdc2(6–20) as a substrate for various Src-family and non-Src-family protein tyrosine kinases suggests that YIYGSFK is a much more specific and efficient substrate for the Src-family protein tyrosine kinases. © Munksgaard 1995.  相似文献   

7.
Cionin, a protochordate-derived octapeptide amide related to the gastrin/cholecystokinin family of peptides, contains two consecutive tyrosine sulfate residues. In order to gain insight into the role of the respective tyrosine sulfate residue in biological activity, cionin and its derivatives in which one of the two tyrosine sulfate residues was replaced by tyrosine, were prepared by two Fmoc-based solid-phase approaches. In approach ( 1 ) Fmoc-Tyr(SO3Na)-OH was employed as a building block to assemble the Tyr(SO3Na)-containing peptide-resin, and a global deprotection cleavage was conducted with 90% aqueous TFA in the presence of m-cresol and 2-methylindole at 4°C. In approach ( 2 ) the Tyr(Msib) [Msib =p-(methylsulfinyl)benzyl] derivative was used for the peptide-chain assembly to achieve sulfation on the selective Tyr residue. Partially protected peptide with the Msib Msz protecting groups [Msz =p-(methylsulfinyl)benzyloxycarbonyl], obtained after peptide-resin cleavage, was treated with DMF-SO3 complex in the presence of ethanedithiol to achieve the sulfation of free Tyr residue and the reduction of the Msib/Msz groups to TFA-labile Mtb/Mtz groups [Mtb =p-(methyithio)benzyl, Mtz =p-(methylthio)benzyloxycarbonyl]. Final deprotection of the Mtb/ Mtz groups with 90° aqueous TFA in the presence of m-cresol and 2-methylindole gave the desired cionin derivative, which contains the tyrosine sulfate residue at the selective position. Yields obtained with approach ( 2 ) were considerably higher than those obtained with approach ( 1 ). Cionin and mono-Tyr(SO3H)-containing derivatives were assayed on exocrine pancreas in dogs.  相似文献   

8.
Abstract: Cross‐linked polystyrene?ethyleneglycol acrylate resin (CLPSER) was developed for the solid‐phase synthesis of peptide by introducing a cross‐linker, O,O′‐bis(2‐acrylamidopropyl)polyethylene glycol1900 (Acr2PEG), into polystyrene. The cross‐linker was prepared by treating acryloyl chloride with O,O′‐bis(2‐aminopropyl) polyethylene glycol1900[(NH2)2PEG] in the presence of diisopropylethylamine. The copolymer was prepared either by bulk or inverse suspension copolymerization of Acr2PEG1900 and styrene using sorbitan monolaurate as the suspension stabilizer, and a mixture of ammonium peroxodisulfate and benzoyl peroxide as the radical initiators. The resin was characterized using gel‐phase 13C NMR, infrared (KBr) spectroscopic techniques and the morphological features of the resin were investigated using scanning electron microscopy photographs. CLPSER showed excellent swelling in a broad range of solvents and was found to be chemically inert to various reagents and solvents used in solid‐phase peptide synthesis. To demonstrate the usefulness of the new resin in polypeptide synthesis, the support was derivatized with an ‘internal reference’ amino acid (norleucine) and a handle 4‐(4‐hydroxymethyl‐3‐methoxy)butyric acid. The new resin was compared with commercial supports such as Merrifield and Sheppard resins by synthesizing an acyl carrier protein (65?74) fragment under the same experimental conditions. HPLC profiles revealed the high efficiency of the newly developed support. Resin capability in peptide synthesis was further demonstrated by the solid phase synthesis of a 25‐residue peptide from the E2/NS1 region hepatitis C viral polyprotein.  相似文献   

9.
The structure of a peptide containing C-terminal dehydrophenylalanine, Z-Gly-(Z)-δPhe (C19H18N2O5, MW = 354) was determined from single-crystal X-ray diffraction data. Needle-shaped crystals were grown from a 1:1 mixture of methanol-acetone in the monoclinic space group P21 with a= 14.717(4), b= 4.941(2), c= 12.073(4) Å, β= 103.72(4)?; V= 852.86(8) Å3, Z= 2 and Dc= 1.32 g cm ?3. The structure was solved by direct methods using SHELXS-86 and refined to a final R-index of 0.032 for 1714 observed reflections. The peptide adopts a conformation folded at the glycine residue, and principal torsion angles are ω0= 167.6(2)?, pHGR;1= -71.8(3)?, ψ1= -31.6(4)?, ωl= - 165.7(3)?, pHGR;2= 65.6(4)?, ψ1/2 = -174.4(3)? and ψ2/2 = 5.2(4)?. Two intermolecular hydrogen bonds, N1—H…Oo and O2—H…O′1, join the folded molecules into columns and link columns to each other, respectively. FTIR spectroscopy shows the presence of three hydrogen bonds. This third one has been interpreted as an intramolecular hydrogen bond of the N2—H…N1 type. © Munksgaard 1994.  相似文献   

10.
L-tyrosyl-L-tyrosine crystallizes as a dihydrate in the orthorhombic system, space group C2221, with a = 12.105(2), b = 12.789(2), c = 24.492(3) Å, Z = 8. The structure was solved by direct methods and refined to a final R-value of 0.059 for 1740 observed reflections. The molecule exists as a zwitterion, the peptide unit is trans planar, and the backbone torsion angles correspond to an extended conformation, with e1 = 149.4°, e2 = - 161.2°, e2 = 158.3°. The values of the side-chain torsion angles (χ1, χ2) are (- 58.8°, - 63.1°) for the first tyrosine and (- 171.7°, - 116.5°) for the second. The planes of the aromatic rings are nearly parallel (dihedral angle of 6.1°), and their centers are separated by 10.9 Å. The carboxyl plane forms a dihedral angle of 23.8° with the plane of the peptide bond.  相似文献   

11.
Abstract: A peptide screened from a combinatorial peptide library with the sequence EYKSWEYC performed best as a ligand for affinity chromatography of human blood coagulation factor VIII (FVIII). With this peptide immobilized on monolithic CIM columns via epoxy groups we were able to capture FVIII from diluted plasma. Rational substitution of amino acids by spot synthesis revealed that lysine and cysteine can be exchanged for almost all other proteinogenic amino acids without loss of affinity to FVIII. This offers the possibility of site‐specific attachment via either one of these residues or the N‐ or C‐terminus. The aliphatic positions O5 (tryptophan) and O7 (tyrosine), together with the charged position O6 (glutamic acid), seem to form the core of the binding unit. In the positions with aliphatic amino acids, substitution by tyrosine or phenylalanine, and in the positions with charged amino acids, substitution by aspartic acid or lysine, preserved the affinity to FVIII. The functionality of the selected peptides was confirmed by affinity chromatography. Selective binding and elution could be achieved.  相似文献   

12.
The dehydro-peptide Boc-L-Val-δPhe-L-Ile-OCH3 was synthesized by the azlactone method in the solution phase. The peptide crystallized from a methanol/dimethyl sulfoxide (95:5) mixture in space group P61, with a=b= 15.312(1), c= 22.164(5) Å. The structure was determined by direct methods and refined to an R value of 0.098 for 1589 observed reflections [I≥ 1.5 σ(I)]. The peptide adopts an S-shaped conformation with torsion angles: ø1=-127(1), ψ1= -44(1), ø2, = 67(1), ψ2, = 37(1), ø3,=-82(1)°. The side-chain torsion angles in δPhe of X12= 1(2), X2.12= 7(2) and X2.22 = 177(1)° indicate that the δPhe residue is essentially planar. In valyl residue the two side-chain torsion angles are X11= -65(1) and X21= 177(1), whereas the torsion angles in Ile are X1,13= 72(2), X1,23= -159(2), X23= 150(2)°. This is the first peptide which does not adopt a folded conformation for a sequence with a δPhe at the (i+ 2) position. The molecular packing in the crystals is stabilized by several hydrogen bonds: N1-H1?O1’= 2.77(1) Å, N2-H2?O1’= 2.95(1) Å, N3-H3?O2=2.85(1) Å and a possible weak interaction N2-H2?O1’3.29(1) Å- within the columns of molecules along the c-axis and van der Waals forces between the columns. © Munksgaard 1996.  相似文献   

13.
The peptide N-Boc-l -Phe-dehydro-Abu-NH-CH3 was synthesized by the usual workup procedure. The crystals grown from methanol at 4°C belong to the space group P212121 with a= 7.589(2), b= 13.690(4), c= 21.897(6) Å, Z= 4 and dc= 1.149(5) g cm?3 for C19H29N3O5·CH3OH. The peptide crystals were highly sensitive to radiation. The final agreement factor R was 0.055 for 1109 observed reflections (I > 2σ) with data extending to a 2θ value of 103°. The methanol oxygen atom is split into two occupancies. Both sites are involved in identical hydrogen bonding. As a result of substitution of a dehydro-Abu residue at the (i+ 2) position the peptide adopts an ideal β-turn II′ conformation with torsion angles of corner residues as φ1=63(1)°, ψ1= - 127(1)°, φ2= -66(1)° and ψ2= - 10(1)°, and an intramolecular hydrogen bond N—H ? O of length 3.01(1) Å. This shows that the conformational constraints produced by dehydro-Abu are similar in nature to but different in magnitude than those produced by dehydro-Phe and dehydro-Leu. The methanol–peptide interactions show characteristic features of multiple hydrogen-bond formations involving polar sites of participating peptide and methanol molecules. The packing of the molecules in the unit cell is stabilized by interactions through methanol molecules with the help of several hydrogen bonds.  相似文献   

14.
Substitution of the -OSO3H group in the sulfated-tyrosine by the non-hydrolyzable -CH2SO3H group was the first described modification of the sulfate ester that does not affect CCK8 activity. In addition to its capacity to mimic the sulfated tyrosine residue, the amino acid Phe(p-CH2SO3Na) was shown to be stable in acidic media, including HF containing mixtures. The synthesis of Boc-Phe(p-CH2SO3Na)-OH in racemic and resolved forms and its introduction into the sequence of CCK8 by solid phase using standard Boc/benzyl synthesis conditions and BOP as coupling reagent is now reported. The two CCK8 analogues containing the l - or the d -Phe(p-CH2SO3Na) residue, obtained in satisfactory yields, were separated by HPLC and the stereochemistry of Phe(p-CH2SO3Na) residue in each peptide was established by NMR spectroscopy and confirmed by a separate solid phase synthesis in which the pure l isomer was used. Both CCK8 analogues displayed high affinities for peripheral and central receptors (KI ~ 1 nm ) and proved to be full agonists in the stimulation of pancreatic amylase secretion. The ?stabilized-CCK8 peptide”, easily prepared by solid phase, could replace the native peptide in biochemical and pharmacological studies. Moreover the modified amino acid Phe (p-CH2SO3Na) could also be used in solid phase synthesis to prepare a wide variety of CCK analogues and more generally, peptides analogues containing the acid-labile O-sulfated tyrosine.  相似文献   

15.
Cobalt(III) ammine complexes of the type cis-[CoL4(4-AMB)O-AA-Boc](CF3SO3)2, where L4= bisethylenediamine (en)2 or tetraammine (NH3)4, and 4-AMB = 4-(aminomethyl)benzoic acid, have been synthesized and used as linkers to polystyrene resins for solid-phase synthesis of protected peptides. Boc/t-Bu-protected [Leu5]enkephalin was assembled on the two different Co(III) resins, and then cleaved from the resins by reduction of the Co(III) center in 93–96%; yield. HPLC-purified protected [Leu5]enkephalin was obtained in 67–69% overall yield and characterized by amino acid analysis and 1H NMR. Stepwise synthesis on the Co(en)2-resin was also used in the assembly of Boc-Asp(OcHex)-Arg(Mts)-Gly-Asp(OcHex)-Ala-Pro-Lys(2Cl-Z)-Gly-OH, a sequence from collagen α1 Type 1. The protected peptide was cleaved from the Co(III) resin in 74% yield, and the HPLC-purified nonapeptide was characterized by amino acid analysis, 1H NMR and liquid secondary-ion mass spectrometry (LSIMS). New routes are described for the synthesis of isomerically pure Co(III) anchor complexes. The Co(III) resins were found to be compatible with both the tert-butyloxycarbonyl (Boc) and the 9-fluorenylmethoxycarbonyl (Fmoc) Nα-protecting group strategies used in solid-phase peptide synthesis.  相似文献   

16.
Crystals of the tripeptide, glycyl-glycyl-sarcosine (C7H13N3O4) from aqueous methanol are orthorhombic, space group Pbcn with cell parameters at 294 K of a = 8.279(1), b = 9.229(4), c = 24.447(5) Å, V = 1868.0 Å3, M.W. = 203.2, and Z = 8. The crystal structure was solved and refined using CAD-4 data (1171 reflections ≥ 3σ) to a final R-value of 0.053. The first peptide linkage is trans and planar whereas the second peptide link between Gly and sarcosine is cis and appreciably non-planar (w = 7.4°). The peptide backbone has an extended conformation at the N-terminal part but adopts a polyglycine-II type of conformation at the C-terminal part. The backbone torsion angles are: Ψ1, =? 173.9, w1=? 177.8, (φ, Ψ2) = (-178.8, -170.8), w2= 7.4, (φ3, Ψ3) = (-81.6, 165.6°).  相似文献   

17.
The synthesis of a novel technetium‐99m labelled derivative of L ‐tyrosine as a potential tumour imaging agent for nuclear medicine diagnosis is reported. The synthesis involved the labelling precursor fac‐[99mTc(OH2)(CO)3]+ which was synthesized using the commercially available Isolink®‐labelling kit and the tyrosine derivative O‐(N,N‐bis(carboxymethyl)aminoethyl)‐L ‐tyrosine trifluoroacetate. The labelled compound O‐(99mTc(I)‐tricarbonyl‐N,N‐bis(carboxymethyl)aminoethyl)‐L ‐tyrosine was obtained in a radiochemical yield of 70–80% within 60 min with a radiochemical purity greater than 98% without any HPLC purification step. Purification was achieved merely by solid phase extraction. Chemical as well as chiral purity was determined using gradient‐ and chiral HPLC. Copyright © 2004 John Wiley & Sons, Ltd.  相似文献   

18.
1,4-Naphthoquinones, XXV: Reaction of the Redox 5-Lipoxygenase Inhibitor 2-(3,5-Di-tert-butyl-4-hydroxyphenyl)-3-hydroxy-1,4-naphthoquinone with O2?? and 3O2 The 5-lipoxygenase inhibitor 2-(3,5-di-tert-butyl-4-hydroxyphenyl)-3-hydroxy-1,4-naphthoquinone ( 2 ), its deoxygenation product 1 as well as the oxygenated species 3 are O2?? quenchers with different power in aqueous solution. In alcoholic solution the antioxidative capacity of 1 does not change, 2 indeed is still only a weak O2?? quencher while 3 shows prooxidative properties. This phenomenon was explored in the O2?? generating oxygenation system (OS) DMSO-CO32-–O2 by preparative techniques. The following reaction sequence could be proven: 3 ? 2 ? 4 (2,6-di-tert-butyl-1,4-benzoquinone). While the step 3 ? 2 would be O2?? dependent the transition 2 ? 4 occurs on two levels: 1. retro Michael reaction with release of 2,6-di-tert-butylphenol ( 5 ), 2. base catalysed oxygenation of 5 ? 4 by 3O2. The diphenoquinone 6 occurring as byproduct is split with the OS – in contrast to the reaction with 1O2 – in considerable yield to give 4 .  相似文献   

19.
The acquisition of a conditioned avoidance response (CAR) and the effects on monoamine neurotransmittor synthesis was investigated in 28 days old rats after neonatal oxygen deprivation (100% N2 for 20 min or 6% O2-94% N2 for 4.5 hr). The rats subjected to 6% O2-94% N2 for 4.5 hr at 1 day of age were markedly inferior in the CAR acquisition than the control group. The animals subjected to 20 min neonatal anoxia did not differ in avoidance responding compared to controls. Tyrosine hydroxylase and tryptophan hydroxylase activity was studied in vivo in whole brain at 28 days of age by measuring the accumulation of dihydroxyphenylalanine (DOPA) and 5-hydroxytryptophan (5-HTP) respectively after inhibition of aromatic L-amino acid decarboxylase with NSD 1015. An inhibition of tyrosine hydroxylase and tryptophan hydroxylase activity was found after neonatal exposure to 6% O2-94% N2 for 4.5 hr while the rats exposed to 100% N2 for 20 min did not differ from controls. The precursor amino acids tyrosine and tryptophan and the levels of the endogenous monoamines dopamine (DA), noradrenaline (NA) and 5-hydroxytryptamine (5-HT) did not differ from controls in any of the groups. It is suggested that the observed behavioral deficits after prolonged hypoxia may be due to an impaired development of central catecholamine mechanisms.  相似文献   

20.
Crystals of L-leucylglycylglycylglycine, LGGG (C12H22N4O5), grown from an ethanol-water solution, are orthorhombic, space groups P212121, with unit cell dimensions (at 22 ± 3°) a = 9.337(1), b = 10.995(1), c = 15.235(1)Å, v = 1563.4 Å3, Z = 4 with a density of Dobs= 1.29 g-cm-3 and Dcalc= 1.279 g°cm-3. The crystal structure was solved by the application of direct methods and refined to an R value of 0.029 for 1018 reflections with I ± 2s?. The molecule exists as a zwitterion in the crystal. The trans peptide backbone takes up a folded conformation at the middle glycylglycyl link accompanied by a significant nonplanarity up to Δω of 8° at the middle peptide and is relatively more extended at the two ends. The molecules are linked together intermolecularly in an infinite sequence of head to tail 1–4′ hydrogen bonds, as is typical of charged peptides. It is interesting to note that while glycylglycylglycine takes up an extended β-sheet conformation, addition of Leu to the N-terminal results in a bent conformation.  相似文献   

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