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1.
The influence of amino acid side chains [derived from: Ala, Val, Leu, Ile, Phe, Tyr(Bzl), Ser(Bzl), Thr(Bzl), Pro, Trp], incorporated into "aminoalkyl" part of PNA monomers, on the temperature-dependent distributions of rotamers about the tertiary amide bond was studied by means of 1H NMR at 0, 25 and 40 degrees C in CDCl3. The delta G0 values of the energy differences between individual rotamers were calculated. The results may be helpful in the designing of monomers with desirable properties.  相似文献   

2.
Abstract

The aim of this work was the preparation of four new peptide nucleic acid (PNA) monomer backbone by reductive animation of Nα-Boc-protected chiral amino aldehydes, derived from Leu, Phe, Tyr(Bzl), and Thr(Bzl), with methyl glycinate. To the crude 2-substituted methyl N-(2-Boc-aminoethyl)glycinates obtained, thymin-1-ylacetic acid was coupled using TBTU procedure in a one-pot reaction. PNA monomers were isolated and characterized.  相似文献   

3.
We have synthesised a series of new chiral type I peptide nucleic acid monomers in total yields of 36–53%, derived from Val, Ile, Ser(Bzl), Pro, and Trp, employing convenient procedure.  相似文献   

4.
The formation of 3-(1-piperidinyl)alanyl-containing peptides via phosphoryl β-elimination was identified from the application of Fmoc-Ser(PO3Bzl,H)-OH in peptide synthesis as shown by RP-HPLC, ES-MS and 31P-NMR analysis. An N α -deprotection study using the model substrates, Fmoc-Xxx(PO3Bzl,H)-Val-Glu(OtBu)-Resin (Xxx = Ser, Thr or Tyr) demonstrated that piperidine-mediated phosphoryl β-elimination occurred in the N-terminal Ser(PO3Bzl,H) residue at a ratio of 7% to the target phosphopeptide, and that this side reaction did not occur in the corresponding Thr(PO3Bzl,H)- or Tyr(PO3Bzl,H)- residues. The generation of 3-(1-piperidinyl)alanyl-peptides was also shown to be enhanced by the use of microwave radiation during Fmoc deprotection. An examination of alternative bases for the minimization of byproduct formation showed that cyclohexylamine, morpholine, piperazine and DBU gave complete suppression of β-elimination, with a 50% cyclohexylamine/DCM (v/v) deprotection protocol providing the crude peptide of highest purity. Piperidine-induced β-elimination was found only to occur in Ser(PO3Bzl,H) residues that were in the N-terminal position, since the addition of the next residue in the sequence rendered the phosphoseryl residue stable to multiple piperidine treatments. The application of the alternative N α -deprotection protocol using 50% cyclohexylamine/DCM (v/v) is therefore recommended for deprotection of the Fmoc group from the Fmoc-Ser(PO3Bzl,H) residue, with particular benefit anticipated for the synthesis of multiphosphoseryl peptides.  相似文献   

5.
The two protected tetradecapeptides Z·Ser·Cys[Bzl(OMe)]·Val·Ser·Cys[Bzl(OMe]·Gly·Ala·Cys[Bzl(OMe)]·Ala·Gly·Glu(OBut)· Cys[Bzl(OMe)]·Pro·Val·NH·NH·Boc and Z·Ser·Ala·Ile·Thr·Gln·Gly·Asp(OBut)·Thr(But)·Gln·Phe·Val·Ile·Asp(OBut)·Ala·NH·NH·Boc, corresponding to residues 7–20 and 21–34 in the amino acid sequence of Clostridium butyricum apoferredoxin have been synthesized as a first stage in a total synthesis of the apoferredoxin. The former peptide has been deprotected to the tetra-thiol peptide H·Ser·Cys·Val·Ser·Cys·Gly·Ala·Cys·Ala·Gly·Glu·Cys·Pro·Val·NH·NH2, and two tri-thiol and three di-thiol peptide components of this have also been synthesized for iron-sulfur complexing studies.  相似文献   

6.
Neb-TMOF, the trypsin modulating oostatic factor of gray fleshfly Neobellieria bullata, is a hexapeptide with the following sequence: H-Asn-Pro-Thr-Asn-Leu-His-OH. It has been isolated from vitellogenic ovaries in 1994. TMOF, the newly discovered insect peptide, inhibits trypsin biosynthesis in the gut, lowers yolk polypeptide concentration in the hemolymph and strongly inhibits ecdysone biosynthesis by larval ring glands. It is interesting that this short non-protected peptide contains in its molecule two Asn residues at positions 1 and 4 and His at its C-terminus. To obtain information about the role of the His-6 and Asn-4 residues we synthesised two series of Neb-TMOF analogs, modified: (1) in position 6 by D-His (I), His(Bzl) (II) and Phe(p-X) derivatives, where X = NH2 (III), NO2 (IV), OEt (V) and OH (VI) and (2) in position 4 by such amino acid residues as Ser (VII), Thr (VIII), Gly (IX), Asp (X), Glu (XI) and D-Asn (XII). The influence of these peptides on trypsin biosynthesis in N. bullata was determined in vivo. In preliminary investigations, we found that Neb-TMOF, [Phe(NH2)6], and [Phe(NO2)6]-Neb-TMOF inhibited trypsin biosynthesis, whereas [D-His)6]- and [D-His(Bzl)6]-Neb-TMOF were inactive. In further biological studies performed in vitro on heart of Tenebrio molitor we found that Neb-TMOF and [Phe(p-NH2)6-Neb-TMOF showed weak cardioexcitatory activity, about 30% of the cardioexcitatory activity of proctolin, an insect neuromodulating peptide.  相似文献   

7.
 d(TpG) reacts with cis-[Pt(NH3)2(H2O)2]2+ in two steps to yield the platinum chelate cis-[Pt(NH3)2{d(TpG)-N3(1),N7(2)}]. In the latter, hindered rotation of the bases leads to an equilibrium between two rotamers interconverting slowly on the NMR time scale. The structure of the two rotameric chelates was studied by means of 1H NMR and molecular modeling techniques. The major and minor rotamers could be assigned unambiguously to the two head-to-head conformational domains which are characterized by syn/anti and anti/anti sugar-base orientations, respectively. Molecular models derived for both rotamers show that the orientations of the bases are mutually quasi-enantiomeric. The interconversion between the two rotamers (k ≈ 1 s–1 at 293 K) is approximately 104 times faster than the analogous rotamer interconversion observed in cis-[Pt(NH3)2{r(CpG)-N3(1),N7(2)}]+ [Girault J-P, Chottard G, Lallemand J-Y, Huguenin F, Chottard J-C (1984) J Am Chem Soc 106 : 7227–7232], suggesting that the steric clash of the exocyclic amino group of the platinum-bound cytosine with the ligands in cis position is more severe than that of the two thymine oxo groups. Received: 23 June 1997 / Accepted: 30 September 1997  相似文献   

8.
Summary Neb-TMOF, the trypsin modulating oostatic factor of gray fleshflyNeobellieria bullata, is a hexapeptide with the following sequence: H-Asn-Pro-Thr-Asn-Leu-His-OH. It has been isolated from vitellogenic ovaries in 1994. TMOF, the newly discovered insect peptide, inhibits trypsin biosynthesis in the gut, lowers yolk polypeptide concentration in the hemolymph and strongly inhibits ecdysone biosynthesis by larval ring glands. It is interesting that this short non-protected peptide contains in its molecule two Asn residues at positions 1 and 4 and His at its C-terminus. To obtain information about the role of the His-6 and Asn-4 residues we synthesised two series of Neb-TMOF analogs, modified: (1) in position 6 byd-His (I), His(Bzl) (II) and Phe(p-X) derivatives, where X=NH2 (III), NO2 (IV), OEt (V) and OH (VI) and (2) in position 4 by such amino acid residues as Ser (VII), Thr (VIII), Gly (IX), Asp (X), Glu (XI) andd-Asn (XII). The influence of these peptides on trypsin biosynthesis inN. bullata was determinedin vivo. In preliminary investigations, we found that Neb-TMOF, [Phe(NH2)6], and [Phe(NO2)6]-Neb-TMOF inhibited trypsin biosynthesis, whereas [d-His)6]- and [d-His(Bzl)6]-Neb-TMOF were inactive. In further biological studies performedin vitro on heart ofTenebrio molitor were found that-TMOF and [Phe(p-NH2)6]-Neb-TMOF showed weak cardioexcitatory activity, about 30% of the cardioexcitatory activity of proctolin, an insect neuromodulating peptide.  相似文献   

9.
New cysteine-containing derivatives of glycyrrhizic acid were synthesized by its coupling with Cys(Bzl) esters or the Cys(Bzl)-Val-OBu t dipeptide by the active ester method (DCC/HOSu) or by Woodward's reagent K. The derivatives with Cys(Bzl) and Cys(Bzl)-Val residues attached to the carbohydrate part of the molecule stimulated the primary immune response and the reaction of delayed-Type hypersensitivity in mice at a dose of 2 mg/kg.  相似文献   

10.
Summary A series of phosphopeptides Tyr(PO3H2)-Val-Pro-Xxx-Leu (Xxx=Met, Met(O), Nle, Dab or Cys), derived from the native platelet-derived growth factor- receptor (PDGF-) sequence, has been prepared to study their interaction with the src-homology 2 (SH2) domains of the p85 subunit of PI3 kinase. The phosphopeptides were synthesized using Fmoc methodology incorporating N-Boc dibenzyl-protected phosphotyrosine (Boc-Tyr[PO3(Bzl)2]) as the N-terminal amino acid, since the benzyl groups can be removed during resin cleavage with TFA. Only peptides containing methionine were found to exist partially as S-benzyl sulfonium salts after TFA cleavage from the resin. The desired peptide could be obtained from the S-benzyl sulfonium salt by hydrogenolysis.  相似文献   

11.
Summary Procedures for preparing precusors of the artificial sweetner, Moz-Asp(Bzl)- D-Ala-R, R=NH2, n-Propyl, isopropyl, in anhydrous t-butanol catalyzed by an industrial alkaline protease alcalase using a kinetic-controlled approach have been developed.Abbreviation Moz p-methoxybenzyloxycarbonyl - OBzl benzyl ester - OPrn n-propyl ester - Opri isopropyl ester  相似文献   

12.
Novel ionic mixed-ligands complexes of the types cis- and trans-[Pt(pz)2(Ypy)2](NO3)2 (where Ypy is a pyridine derivative and pz = pyrazine) were synthesized and studied mainly in the solid state by IR spectroscopy and in aqueous solution by multinuclear (195Pt, 1H and 13C) magnetic resonance spectroscopy. The trans isomers with ligands containing a methyl group in ortho position on the pyridine ring could not be synthesized. The results of the solution NMR characterization have shown that the isolated compounds are pure. In 195Pt NMR, the cis complexes containing a methyl group in ortho positions were observed at lower field (average −2337 ppm) than the other cis compounds (average −2427 ppm), which is explained by the solvent effect. The trans isomers were observed at very slightly lower fields (average −2422 ppm) than the equivalent cis complexes (average −2427 ppm). In 1H NMR, the coupling constants 3J(195Pt-1HYpy) and 3J(195Pt-1Hpz) are larger in the cis compounds (∼40 Hz) than in the trans complexes (∼31 Hz). A few 4J(195Pt-1Hpz) were observed (∼16 Hz). In 13C NMR spectroscopy, the coupling constants 3J(195Pt-13Cpz) and 3J(195Pt-13CYpy) are also larger in the cis configuration (∼30 and ∼38 Hz, respectively) than in the trans isomers (∼20 Hz). One 4J(195Pt-13Cpz) could be calculated (17 Hz). The presence of the syn and anti rotamers were observed in all the cis complexes containing a pyridine derivative with a -CH3 group in ortho position. They were observed in 195Pt, 1H and 13C NMR spectroscopy. The proportion of the two rotamers is about 55% and 45%.  相似文献   

13.
Abstract

1,3,5-Trimethyl-N4-hydroxycytosine, an analogue of the promutagenic N4-hydroxycytosine and 5-methyl-N4-hydroxycytosine nucleosides, crystallizes in the monoclinic space group P 21/n with cell dimensions at ?147°C: a = 7.1481(7), b = 9.2565(5), c = 13.3086(12) Å, β = 97.90(2)°, V = 872.24(13) Å3, ρc = 1.426 Mg m?3, Z = 4, F(000) = 401.39, μ = 0.91 mm?1, λ(Cu) = 1.54056 Å, 20(max) = 139.3°. The crystal structure has been solved by X-ray difraction and refined to R = 3.7 % for 1457 reflections. Notwithstandin the steric hindrance imposed by methyl groups at both N(3) and C(5), the exocyclic N4-OH group is located essentially in the plane of the ring, giving rise to an “overcrowded” molecule, like that of 1,5,N4,N4-tetramethylcytosine. The conformational parameters have also been compared with those of a number of related and previously reported N(1)-substituted cytosines. In the present compound the N4-OH rotamer is in the anti conformation relative to the ring N(3), hence similar to that of one of the rotamers in N(1)-substituted N4-hydroxycytosine, which permits normal Watson-Crick base pairing of the latter, relevant to the mechanism of hydroxylamine mutagenesis.  相似文献   

14.
Summary The efficiency of various coupling methods for the incorporation of the three monobenzyl phosphorodiesterprotected derivatives, Fmoc-Tyr(PO3Bzl,H)-OH, Fmoc-Ser(PO3Bzl,H)-OH and Fmoc-Thr(PO3Bzl,H)-OH, was examined through the test synthesis of Ala-Ser-Gln-Gly-Xxx(PO3H2)-Leu-Glu-Asp-Pro-Ala-NH2 (Xxx=Tyr, Ser, Thr) using the Multipin method of multiple peptide synthesis. The coupling methods examined were (1) PyBrop/DIEA; (2) BOP/HOBt/NMM; (3) BOP/HOBt/DIEA; (4) HBTU/HOBt/DIEA; (5) HATU/HOAt/DIEA; (6) HATU/DIEA; (7) DIC/HOBt; (8) DIC/HOBt/DIEA; (9)DIC/HOAt; (10) DIC/HOAt/DIEA. While all four DIC-based coupling procedures resulted in incomplete incorporation, both the HBTU/HOBt/DIEA and HATU/HOAt/DIEA coupling procedures provided most efficient incorporation of the three Fmoc-Xxx (PO3Bzl,H)-OH derivatives. In the subsequent synthesis of the α-helical Tyr(P)-peptide, Glu-Thr-Gly-The-Lys-Ala-Glu-Leu-Leu-Ala-Lys-Tyr(PO3H2)-Glu-Ala-Thr-His-Lys-NH2, analysis of the crude peptide by electrospray MS confirmed that several residue deletions had occurred but that complete incorporation of the Tyr(P)-residue had been accomplished using HBTU/HOBt/DIEA coupling of Fmoc-Tyr(PO3Bzl,H)-OH. Multipin is a trademark of Chiron Technologies Pty. Ltd., Clayton, Victoria, Australia.  相似文献   

15.
Abstract

The three dimensional structure of the activiral agent, 5-methoxymethyl-2′-deoxyuridine (MmdUrd) was determined by x-ray diffraction methods. MMdUrd crystallized in space group P212121 of the orthorhombic system with a = 9.166(1)A, b, = 25.348(1)Amm c = 5.270(1)A and Z = 4. The conformation of the glycosyl bond is anti (χ = 233.30), the deoxyribose ring has the C(2′)-endo envelope conformation (2E), the CH2OH side chain has the g+ conformation and the methoxy group at the C(5) position is on the same side of pyrimidine plane as the 0(4′) oxygen. NMR spectroscopy was used to determine the conformation in solution. The spectra indicate that the sugar ring exists in a 60:40 equilibrium of the S- and N-states. The population of the three rotamers about the exocyclic c(4′)–C(5′) bond were estimated to be g+:t:g::61%:31%:8%. The correlaiton of molecular conforation with antiviral activity is discussed.  相似文献   

16.
Mixed-ligand complexes of the type cis- and trans-Pt(Ypy)(pm)Cl2 where Ypy = pyridine derivative and pm = pyrimidine were synthesized and characterized by IR spectroscopy and by multinuclear (195Pt, 1H and 13C) magnetic resonance spectroscopy. The cis compounds were prepared from the reaction of K[Pt(Ypy)Cl3] with pyrimidine (1:1 proportion) in water, while most of the trans isomers were synthesized from the isomerization of the cis compounds. The cis isomers could not be isolated with the Ypy ligands containing two -CH3 groups in ortho positions. When the aqueous reaction of K[Pt(Ypy)Cl3] with pyrimidine was performed in a Pt:pm ratio = 2:1, the pyrimidine-bridged dinuclear species were formed. Only the most stable trans-trans isomers could be isolated pure. In IR spectroscopy, the cis monomers showed two ν(Pt-Cl) bands, while the trans monomers and dimers showed only one ν(Pt-Cl) band. The 195Pt NMR signals of the cis monomers were found at slightly higher fields than those of the corresponding trans isomers. The δ(195Pt) of the dimers were found close to those of the trans monomers. The NMR results were interpreted in relation to the solvent effect, which seems important in these complexes. The coupling constants J(195Pt-1H) and J(195Pt-13C) are larger in the cis geometry. The crystal structures of the compounds cis-Pt(2,4-lut)(pm)Cl2, trans-Pt(2,6-lut)(pm)Cl2 and trans,trans-Cl2(2,6-lut)Pt(μ-pm)Pt(Ypy)Cl2 were studied by X-ray diffraction methods and the results have confirmed the configurations suggested by IR and NMR spectroscopies.  相似文献   

17.
 A PtII complex containing N4 bound neutral 1-methylcytosine (1-MeC), trans–[Pt(NH3)2(1-MeC-N4)2](ClO4)2 (5), has been prepared and characterized by X-ray analysis. The complex contains the rare iminooxo tautomer form of the cytosine nucleobase. PtII binding is through the exocyclic N4 position of the nucleobases, with Pt and the N3 positions in a syn orientation. As a consequence, the proton at N3 is pointing toward the heavy metal, thereby allowing an agostic Pt···HN interaction. Formation of 5 is achieved via oxidation of the linkage isomer trans–[Pt(NH3)2(1-MeC-N3)2]2+ (1) to a PtIV species (2), followed by metal migration to N4, and subsequent reduction to PtII. This process is a text-book example for a redox-assisted metal migration at a heterocyclic ligand. The existence of various rotamers of 5 in aqueous solution is evident from 1H NMR spectroscopy. The possible role of these rotamers of the metalated rare tautomer, and in particular of those having Pt and the N3 position in an anti arrangement, with regard to base mispairing is discussed. Received: 27 February 1996 / Accepted: 10 June 1996  相似文献   

18.
It was demonstrated for the first time that the distribution of side-chain rotamers in the a-and d-positions of α-helices of coiled-coil (cc) proteins follows a certain trend, rather then being random. For instance, most side chains adopt t rotamers in the a-positions and g? rotamers in the d-positions of helical dimers. Vice versa, most side chains adopt g? rotamers in the a-positions and t rotamers in the d-positions of tetramers. It was concluded that selection of the side-chain rotamers depends on the packing of α-helices and, consequently, depends on the structural context.  相似文献   

19.
The binding of the enkephalin dimer [d-Ala2, Leu5-NH-CH2-]2 (DPE2) is characterized by (1) its high affinity for receptors on NG108-15 hybrid cells, the affinity constantK=4.7×109 M–1 is up to 8-fold that of monomers (0.6 to 1.0×109 M–1), and (2) a maximal binding capacity equal to one half that of the monomers. Kinetic studies showed that DPE2 binds with a 2-fold higher rate, k1=6.3×107 M–1min–1, than monomers (2.4 to 3.8×107 M–1min–1), and dissociates at a slower rate than monomers. Dissociation of DPE2 was consistently bi- or multiphasic but increased about 12% only after 3 hr of dissociation in the presence of a large excess of unlabeled enkephalin. The dissociation kinetics of monomers varied with enkephalin and experimental conditions used. Consistent with the value for the maximal binding capacity, the kinetic studies are interpreted in support of the hypothesis that DPE2 binds by cross-linking two subunits of one receptor.  相似文献   

20.
Phytochemical investigation of Mimosa xanthocentra Mart. (Leguminosae: Mimosoideae), an herb comprising the diet of marsh deer and pampas deer in the Brazilian Pantanal, led to the isolation of flavones isovitexin-2″-O-α-l-rhamnopyranoside 1 and vitexin-2″-O-α-l-rhamnopyranoside 2, and a mixture of flavonols avicularin 3a and reynoutrin 3b. At room temperature, compound 1 was observed in the 1H and 13C NMR spectra as a mixture of two rotamers in equilibrium in a DMSO-d6 solution. Molecular modeling using MM2 calculations led to the first proposal of three-dimensional solution structure of both observed conformers. The energy barrier between both rotamers was evaluated theoretically by molecular modeling and experimentally by variable-temperature NMR studies and calculation of ΔG3 of rotation using Eyring equation. This is the first report on flavonoids from M. xanthocentra.  相似文献   

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