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1.
Summary. A concise preparation of N
α-Fmoc-N
ɛ-(Boc, methyl)-lysine and its application in the synthesis of site-specifically lysine monomethylated peptide is described.
N
α-Fmoc-N
ɛ-(Boc, methyl)-lysine is obtained, via consecutive reductive benzylation and reductive methylation in a one-pot reaction,
followed by debenzylation through catalytic hydrogenolysis and Boc protection in another one-pot reaction. A peptide containing
monomethylated lysine is successfully synthesized by incorporating N
α-Fmoc-N
ɛ-(Boc, methyl)-lysine as a building block via solid-phase peptide synthesis. 相似文献
2.
Maria Luisa Di Gioia Antonella Leggio Angelo Liguori Francesca Perri Carlo Siciliano Maria Caterina Viscomi 《Amino acids》2010,38(1):133-143
A convenient route for the synthesis of lipophilic N-Fmoc-N-methyl-α-amino acids and N-nosyl-N-methyl-α-amino acids, interesting building blocks to be used for the preparation of N-methylated peptides, is presented. Both nosyl- and Fmoc-protected monomers are accessible, so these compounds can be used
in solution as well as in solid phase peptide synthesis. The methodology is based on the use of benzhydryl group to protect
temporarily the carboxyl function of N-nosyl-α-amino acids and on the subsequent methylation of the N-nosyl-α-amino acid benzhydryl esters with diazomethane. The benzhydryl esters offer several beneficial features such as simple
preparation, stability to methylation and selective deprotection under mild conditions. The overall procedure is highly efficient
in that the adopted conditions keep the chiral integrity of amino acid precursors and the process does not require chromatographic
purification of the methylated products. 相似文献
3.
Stéphane Eifler Isabelle Leblond Elisabeth Trifilieff Jean-Pierre Lepoittevin 《International journal of peptide research and therapeutics》1997,4(4-6):467-472
Summary N-α-Fmoc-N-τ-methyl-L-histidine was prepared in three steps fromN-α-Boc-L-histidine by treatment with methyliodine in DMF at−10°C, deprotection of theN-α position in pure TFA and subsequent reprotection by Fmoc-chloroformate in a 5% Na2CO3/dioxane mixture.N-α-Fmoc-N-τ-methyl-L-histidine was then used for the solid-phase synthesis of two analogues of the OVA323–336 T-epitope, methylated on His331 and on His328/331, respectively. These peptides were tested for their ability to activate 3 DO-54.8 T-cell hybridoma when presented by fixed
A-20.1.11 antigen presenting cells, and no significant difference was observed in IL-2 production. 相似文献
4.
Alessandro Moretto Marta De Zotti Marco Crisma Fernando Formaggio Claudio Toniolo 《International journal of peptide research and therapeutics》2008,14(4):307-314
“Mono-N-methyl scan” is a rational approach for the optimization of the peptide biological properties. N-Methylation of the –CONH– functionality is also a useful tool for discriminating solvent exposed from intramolecularly H-bonded
secondary amide groups in peptides. We are currently extending this reaction to linear peptides based on Cα-tetrasubstituted α-amino acids. Following our study on the synthesis and conformation of the mono-N-methylated peptides from Cα-methylated residues, in this work we investigated the N-methylation reaction on homo-peptides to the pentamer level from the Cα-ethylated residue Cα,α-diethylglycine. Under the classical experimental conditions used, exclusively mono-N-methylation (on the N-terminal, acetylated residue) takes place, as unambiguously shown by mass spectrometry, 2D-NMR, and X-ray diffraction techniques.
This backbone modification does not seem to involve any significant change in the peptide conformation in the crystalline
state.
Dedicated to the memory of Prof. Miroslav T. Leplawy (Technical University of Łodz, Poland), who performed the first synthesis
of the extremely sterically demanding Cα,α-diethylglycine peptides. 相似文献
5.
J. Custot Jean-Luc Boucher Sandrine Vadon Catherine Guedes Sylvie Dijols Marcel Delaforge Daniel Mansuy 《Journal of biological inorganic chemistry》1996,1(1):73-82
The effects of various compounds bearing an N-OH group such as N-hydroxy-guanidines, amidoximes, and hydroxylamines, on bovine and rat liver arginases was studied. Some of these compounds
with an l-α-amino acid function at an appropriate distance from the N-OH group acted as strong competitive liver arginase inhibitors,
displaying Ki values between 4 and 150 μM. Two compounds, N
ε-hydroxy-l-lysine and N
ω-hydroxy-d,l-indospicine, which exhibited Ki values of 4 and 20 μM (at pH 7.4), were the most potent inhibitors of arginase described
to date. The distance between the α-amino acid and N-OH functions appeared to be crucial for potent inhibition of arginase,
as N
δ-hydroxy-l-ornithine, which has one -CH2 group less than N
ε-hydroxy-l-lysine, exhibited a 37-fold higher Ki value than N
ε-hydroxy-l-lysine. Based on these results, a model for the interaction of N
ω-hydroxyamino-l-α-amino acids with the arginase active site is proposed. This model involves the binding of the N-OH group of the inhibitors
to the arginase Mn(II) center and suggests that N
ε-hydroxy-l-lysine is a good transition state analog of arginase. 相似文献
6.
Frochot Céline Vanderesse Régis Driou Alain Linden Guy Marraud Michel Thong Cung Manh 《International journal of peptide research and therapeutics》1997,4(4-6):219-225
Summary Using the Boc-strategy, a step-by-step synthesis on the PAM solid support of three aza-, iminoaza- and reduced aza-peptide
homologues is described. From the same hydrazinocarbonyl peptide-PAM precursor, the coupling of either a Boc-amino acid or
a Boc-amino aldehyde gives rise to an aza-peptide or an iminoaza-peptide, containing the Cα-CO-NH-Nα-CO-NH-Cα or Cα-CH=N-Nα-CO-NH-Cα surrogate, of the peptide motif, respetively. In situ reduction of the latter by NaBH3CN leads to a reduced aza-peptide containing the Cα-CH2-NH-Nα-CO-NH-Cα moiety. The key step synthesis of the hydrazinocarbonyl peptide-PAM precursor is carried out by coupling on the growing peptide
chain theN-Boc-azaamino acid chloride obtained by the action of triphosgene on the, correspondingN-Boc-hydrazine. These modifications have been introduced in position 1–2 of the YLGYLEQLLR benzodiazepine-like decapeptide. 相似文献
7.
Beltrán Maite Maseda Marta Robles Jordi Pedroso Enrique Grandas Anna 《International journal of peptide research and therapeutics》1997,4(3):147-155
Summary Covalently linked peptide-oligonucleotide hybrids are good candidates for antisense or anti-gene therapeutics. The use of
homoserine as the linking amino acid allows nucleopeptide analogues with a base-stable amino acid-nucleoside phosphate diester
linkage to be obtained. Three Nα, O-protected homoserine derivatives (N
α-Boc-Hse(DMT)-O− HTEA+ (I),N
α-Fmoc-Hse(MMT)-O−Hpyr+ (II) andN
α-Phac-Hse(DMT)-O−HTEA+(III) were prepared after transient silylation,N
α-acylation, desilylation and protection of the hydroxyl group. The first can be placed at any position in the peptide sequence,
while the other two must be placed at theN-terminus to afford nucleopeptides with the N-terminal amine group free or permanently blocked, respectively. 相似文献
8.
Identification and Suppression of β-Elimination Byproducts Arising from the Use of Fmoc-Ser(PO3Bzl,H)-OH in Peptide Synthesis 总被引:1,自引:0,他引:1
Troy J. Attard Neil M. O’Brien-Simpson Eric C. Reynolds 《International journal of peptide research and therapeutics》2009,15(1):69-79
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
9.
Vommina V. Sureshbabu N. S. Sudarshan Rao Venkataramanarao 《International journal of peptide research and therapeutics》2008,14(2):149-156
A simple protocol for the synthesis of linear peptidylcarbamates employing Fmoc-β-aminoalkoxy carbonyl chlorides is described. The N-Fmoc-β-aminoalkoxy carbonyl chlorides were prepared by the reaction of phosgene or triphosgene with Fmoc-protected β-amino alcohol which were isolated as solids. These oxycarbonyl chlorides were also converted to the corresponding pentachlorophenyl
carbonates by reacting with pentachlorophenol. Fmoc-β-aminoalkoxy carbonyl chlorides as well as pentachlorophenol carbonates were successfully used as monomeric building blocks
for the synthesis of several peptidyl carbamates. 相似文献
10.
11.
Background
Thymosin α1 (Tα1), a 28-amino acid N α -acetylated peptide, has a powerful general immunostimulating activity. Although biosynthesis is an attractive means of large-scale manufacture, to date, Tα1 can only be chemosynthesized because of two obstacles to its biosynthesis: the difficulties in expressing small peptides and obtaining N α -acetylation. In this study, we describe a novel production process for N α -acetylated Tα1 in Escherichia coli. 相似文献12.
Unravelling the complex correlation between chemical shifts of 13
C
α, 13
C
β, 13
C′, 1
H
α, 15
N, 1
H
N
atoms in amino acids of proteins from NMR experiment and local structural environments of amino acids facilitates the assignment
of secondary structures of proteins. This is an important impetus for both determining the three-dimensional structure and
understanding the biological function of proteins. The previous empirical correlation scores which relate chemical shifts
of 13
C
α, 13
C
β, 13
C′, 1
H
α, 15
N, 1
H
N
atoms to secondary structures resulted in progresses toward assigning secondary structures of proteins. However, the physical-mathematical
framework for these was elusive partly due to both the limited and orthogonal exploration of higher-dimensional chemical shifts
of hetero-nucleus and the lack of physical-mathematical understanding underlying those correlation scores. Here we present
a simple multi-dimensional hetero-nuclear chemical shift score function (MDHN-CSSF) which captures systematically the salient
feature of such complex correlations without any references to a random coil state of proteins. We uncover the symmetry-breaking
vector and its reliability order not only for distinguishing different secondary structures of proteins but also for capturing
the delicate sensitivity interplayed among chemical shifts of 13
C
α, 13
C
β, 13
C′, 1
H
α, 15
N, 1
H
N
atoms simultaneously, which then provides a straightforward framework toward assigning secondary structures of proteins.
MDHN-CSSF could correctly assign secondary structures of training (validating) proteins with the favourable (comparable) Q3
scores in comparison with those from the previous correlation scores. MDHN-CSSF provides a simple and robust strategy for
the systematic assignment of secondary structures of proteins and would facilitate the de novo determination of three-dimensional
structures of proteins. 相似文献
13.
M. B. Keown R. Ghirlando G. A. Mackay B. J. Sutton H. J. Gould 《European biophysics journal : EBJ》1997,25(5-6):471-476
A soluble fragment of the high-affinity IgE receptor FcεRI α-chain (sFcεRIα) binds to the Fc fragment of IgE (IgE-Fc) as a 1:1 complex. IgE-Fc consists of a dimer of the Cε2, Cε3 and Cε4 domains of the ε-heavy chain of IgE. This region of IgE has been modelled on the crystal structure of the Fc region of IgG1, which exhibits twofold rotational symmetry. This implies that IgE should be divalent with respect to its ligands. X-ray
scattering studies reveal however that the twofold rotational symmetry of IgE-Fc is perturbed by a bend in the linker region
between the Cε2 and Cε3 domains. The 1:1 stoichiometry could then arise from the conformational asymmetry or from steric occlusion of one of the
sites by the overhanging Cε2 domains. To test this hypothesis we have expressed a recombinant ε-chain fragment containing Cε3 and Cε4. This product, Fcε3–4, is secreted from cells as a disulphide linked dimer and binds with higher affinity than either IgE or IgE-Fc to cell
surface FcεRI. Titration experiments, together with molecular mass measurements of the Fcε3–4/sFcεRIα complex, reveal that Fcε3–4 binds only a single receptor molecule. This excludes the possibility that steric hindrance by Cε2 accounts for the unexpected stoichiometry.
Received: 31 July 1996 / Accepted: 1 December 1996 相似文献
14.
Hamano Y Yoshida T Kito M Nakamori S Nagasawa T Takagi H 《Applied microbiology and biotechnology》2006,72(1):173-181
ε-Poly-l-lysine (ε-PL) is one of the few naturally occurring biopolymers and is characterized by a peptide bond between the α-carboxyl and ε-amino groups. Previously, we purified and characterized the ε-PL-degrading enzyme (Pld) from Streptomyces albulus, which is an ε-PL producer, and this enzyme was expected to confer self-resistance to the ε-PL produced by the organism itself. The gene encoding Pld was cloned based on the N-terminal amino acid sequence determined in this study, and a sequencing analysis revealed eight open reading frames (ORFs), i.e., ORF1 to ORF8 in the flanking region surrounding the pld gene (present in ORF5). To investigate the biological function of Pld, we constructed a knockout mutant in which the pld gene is inactivated. Studies on ε-PL susceptibility, ε-PL-degrading activity, and ε-PL productivity demonstrated that the pld gene does play a partial role in self-resistance and that S. albulus was found to produce other ε-PL-degrading enzyme(s) in addition to Pld. To the best of our knowledge, this is the first report on a self-resistance gene for a biopolymer possessing antibacterial activity. 相似文献
15.
Modification of protein by carbonyl compounds under in vitro physiological conditions is site-directed. There are few reports
of the site specificity of glycation of proteins using heating conditions of relevance to food processing. The aim of this
study was to determine the site specificity of modification of β-casein (βCN) by glucose and methylglyoxal (MGO). βCN (1.33 M,
3.2%) was heated with either glucose (1.345 M, 4.6%) or MGO (1 mM) at 95°C for up to 4 h. Tryptic digests were prepared and
analysed by ultra performance liquid chromatography electrospray ionisation mass spectrometry (UPLC-ES/MS). The sites of formation
of the Amadori product, N
ε
-(fructosyl)lysine (FL), and the advanced glycation end-products, N
ε
-(carboxymethyl)lysine (CML), MGO-derived dihydroxyimidazolidine (MG-DH) and MGO-derived hydroimidazolone (MG-HI), were located.
FL and CML were detected at K107 and K176 residues in βCN/glucose incubations. Indigenous N
ε
-(lactulosyl)lysine was detected at K107 only. MG-DH and MG-HI were detected at R202 and possibly R183 residues in both βCN/glucose
and βCN/MGO incubations. Glycation of βCN by glucose and MGO resulted in similar site specificity for MG-DH and MG-HI formation. 相似文献
16.
The extracellular matrix component collagen type VI demonstrates potent growth-stimulatory effects and has been associated
with aggressive tumour growth. Although, juvenile angiofibromas (JAs) often exhibit an aggressive growth pattern, the collagen
type VI expression of this fibrovascular tumour has not been addressed so far. RT-PCR, Western blot analysis and immunohistochemistry
were used in this study to analyse collagen type VI, type VI collagen receptor subunits (integrin α1, α2, α10, α11 and β1)
and the type VI collagen receptor NG2 in JAs (N = 15) and nasal mucosa (NM, N = 8) samples. The mRNA expression of all three collagen type VI chains was found to be up-regulated significantly (P < 10−3–10−5, adjusted) in JAs compared to NM tissues. The Western blot analysis proved highly prominent collagen-type VI expression in
JAs. The ApoTome technique revealed strong collagen-type VI signals in tumour endothelium. NG2 (P < 10−3, adjusted) and α11-integrin (P = 0.04, adjusted) showed a significantly higher mRNA expression levels in JAs than in NM samples. NG2, α1-, α2- and β1-intergin
were located to tumour vessels, and additional stromal signals were observed for NG2 and α1-integrin in JAs. This study demonstrates
a prominent collagen-type VI expression in JAs. The collagen-type VI may exert an important growth stimulus in this tumour. 相似文献
17.
Veronique Maes Dirk Tourwé 《International journal of peptide research and therapeutics》2006,12(3):197-202
The retro-N
α-carboxymethyl histidine moiety, short (N
αHis)Ac, functions as an efficient chelator for the 99mTc(CO)3 core which allows the labeling of the peptides with a very high specific activity. However as a general consequence of the neutral [99mTc(CO)3] (N
αHis)Ac-complex, undesired accumulation in kidney and liver may be high. In order to improve the pharmacokinetic properties of the radiolabeled peptides containing this chelate, attempts have been made to conjugate a carbohydrate using the Maillard reaction. Since the (N
αHis)Ac moiety has an unusually reactive N
α, various chemical strategies have been explored to perform the Maillard reaction followed by the Amadori rearrangement on peptides containing this chelator. This indicated that a selective protection of the secondary nitrogen in the chelator is necessary.Australian Peptide Conference Issue. 相似文献
18.
J. Hlaváček J. Pícha V. Vaněk J. Jiráček J. Slaninová V. Fučík M. Buděšínský D. Gilner R. C. Holz 《Amino acids》2010,38(4):1155-1164
A series of N
α-acyl (alkyl)- and N
α-alkoxycarbonyl-derivatives of l- and d-ornithine were prepared, characterized, and analyzed for their potency toward the bacterial enzyme N
α-acetyl-l-ornithine deacetylase (ArgE). ArgE catalyzes the conversion of N
α-acetyl-l-ornithine to l-ornithine in the fifth step of the biosynthetic pathway for arginine, a necessary step for bacterial growth. Most of the
compounds tested provided IC50 values in the μM range toward ArgE, indicating that they are moderately strong inhibitors. N
α-chloroacetyl-l-ornithine (1g) was the best inhibitor tested toward ArgE providing an IC50 value of 85 μM while N
α-trifluoroacetyl-l-ornithine (1f), N
α-ethoxycarbonyl-l-ornithine (2b), and N
α-acetyl-d-ornithine (1a) weakly inhibited ArgE activity providing IC50 values between 200 and 410 μM. Weak inhibitory potency toward Bacillus subtilis-168 for N
α-acetyl-d-ornithine (1a) and N
α-fluoro- (1f), N
α-chloro- (1g), N
α-dichloro- (1h), and N
α-trichloroacetyl-ornithine (1i) was also observed. These data correlate well with the IC50 values determined for ArgE, suggesting that these compounds might be capable of getting across the cell membrane and that
ArgE is likely the bacterial enzymatic target. 相似文献
19.
Rao Venkataramanarao Naremaddepalli S Sudarshan Vommina V Sureshbabu 《International journal of peptide research and therapeutics》2007,13(3):393-397
A general and efficient method has been developed for the alcoholysis of isocyanates derived from the Nα-[(9-fluorenylmethyl)oxy]carbonyl amino acids with various alcohols including hindered ones assisted by MW irradiation. Thus,
the synthesis of N, N1-diurethane protected gem-diamines wherein Fmoc protection on one of the amino groups and Z-/Boc-/Alloc or Bsmoc group on the other amino function
has been accomplished. All the new orthogonally diurethane protected gem-diamines have been obtained as crystalline solid powders in 80 to 94% yield. The bisprotected gem-diamines have been fully characterized by IR, 1H NMR, 13C NMR as well as by mass spectrometry. 相似文献
20.
The presence of dipole-dipole cross-correlated relaxation as well as unresolved E.COSY effects adversely impacts the accuracy
of 1
J
NH splittings measured from gradient-enhanced IPAP-HSQC spectra. For isotropic samples, the size of the systematic errors caused
by these effects depends on the values of 2
J
NHα
, 3
J
NHβ
and 3
J
HNHα
. Insertion of band-selective 1H decoupling pulses in the IPAP-HSQC experiment eliminates these systematic errors and for the protein GB3 yields 1
J
NH splittings that agree to within a root-mean-square difference of 0.04 Hz with values measured for perdeuterated GB3. Accuracy
of the method is also highlighted by a good fit to the GB3 structure of the 1H-15N RDCs extracted from the minute differences in 1JNH splitting measured at 500 and 750 MHz 1H frequencies, resulting from magnetic susceptibility anisotropy. A nearly complete set of 2
J
NHα
couplings was measured in GB3 in order to evaluate whether the impact of cross-correlated relaxation is dominated by the
15N–1H
α
or 15N–1H
β
dipolar interaction. As expected, we find that 2
J
NHα
≤ 2 Hz, with values in the α-helix (0.86 ± 0.52 Hz) slightly larger than in β-sheet (0.66 ± 0.26 Hz). Results indicate that under isotropic conditions, N–HN/N–H
β
cross-correlated relaxation often dominates. Unresolved E.COSY effects under isotropic conditions involve 3
J
HNHα
and J
NHα
, but when weakly aligned any aliphatic proton proximate to both N and HN can contribute.
Electronic supplementary material The online version of this article (doi:) contains supplementary material, which is available to authorized users. 相似文献