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1.
Céline Frochot Régis Vanderesse Alain Driou Guy Linden Michel Marraud Manh Thong Cung 《Letters in Peptide Science》1997,4(4-6):219-225
Using the Boc-strategy, a step-by-step synthesis on the PAM solid supportof three aza-, iminoaza- and reduced aza-peptide homologues is described.From the same hydrazinocarbonyl peptide-PAM precursor, the coupling ofeither a Boc-amino acid or a Boc-amino aldehyde gives rise to an aza-peptideor an iminoaza-peptide containing theC-CO-NH-N-CO-NH-C orC-CH=N-N-CO-NH-C surrogate of the peptide motif, respectively. In situreduction of the latter by NaBH3CN leads to a reducedaza-peptide containing theC-CH2-NH-N-CO-NH-C moiety. The key step synthesis of thehydrazinocarbonyl peptide-PAM precursor is carried out by coupling on thegrowing peptide chain the N-Boc-aza-amino acid chloride obtained by theaction of triphosgene on the corresponding N-Boc-hydrazine. Thesemodifications have been introduced in position 1-2 of the YLGYLEQLLRbenzodiazepine-like decapeptide 相似文献
2.
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
3.
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
4.
5.
Krog-Jensen Christian Christensen Mette K. Meldal Morten 《International journal of peptide research and therapeutics》1999,6(4):193-197
Summary A new and facile synthesis of tyrosine phosphorylated peptides has been developed.N
α-Fmoc-Tyr(tBu)-OPfp was treated with TFA, phosphorylated with phosphorous oxychloride and the resulting phosphoric acid dichloride was
hydrolysed to giveN
α-Fmoc-Tyr(PO3H2)-OPfp1 in an overall yield of 98%. Compound1 was used in solid-phase peptide synthesis of phosphopeptides2, 3 and4, which are fragments of murine adipocyte lipid binding protein. The advantage of using the Pfp ester was the absence of pyrophosphates
and other byproducts. 相似文献
6.
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 Stat91695–708. 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; tR, 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]. 相似文献
7.
Szymańska Aneta Ossowski Tadeusz Łankiewicz Leszek 《International journal of peptide research and therapeutics》2002,9(4-5):193-196
Summary A synthesis ofl-Nɛ-(9,10-dioxo-9,10-dihydroanthracen-1-yl)-lysine [Lys(AQN)], the dabcyl-like chromophore, and its derivatives useful in peptide
chemistry is described. Nα-tert-butoxycarbonyl derivative of the title compound was obtained in a good yield using aromatic nucleophilic substitution reaction.
In this form, or after conversion to the Nα-fluorenylmethoxycarbonyl derivative, it can be directly used in the solid phase peptide synthesis using either Boc- or Fmoc-strategy. 相似文献
8.
Martina Schnölzer Paul Alewood Alun Jones Dianne Alewood Stephen B. H. Kent 《International journal of peptide research and therapeutics》2007,13(1-2):31-44
Simple, effective protocols have been developed for manual and machine-assisted Boc-chemistry solid phase peptide synthesis
on polystyrene resins. These use in situ neutralization [i.e. neutralization simultaneous with coupling], high concentrations (>0.2 m) of Boc-amino acid-OBt esters plus base for rapid coupling, 100% TFA for rapid Boc group removal, and a single short (30 s)
DMF flow wash between deprotection/coupling and between coupling/deprotection. Single 10 min coupling times were used throughout.
Overall cycle times were 15 min for manual and 19 min for machine-assisted synthesis (75 residues per day). No racemization
was detected in the .base-catalyzed coupling step. Several side reactions were studied, and eliminated. These included: pyrrolidonecarboxylic acid
formation from Gln in hot TFA-DMF; chain-termination by reaction with excess HBTU; and, chain termination by acetylation (from
HOAc in commercial Boc-amino acids). The in situ neutralization protocols gave a significant increase in the efficiency of chain assembly, especially for “difficult” sequences
arising from sequence-dependent peptide chain aggregation in standard (neutralization prior to coupling) Boc-chemistry SPPS
protocols or in Fmoc-chemistry SPPS. Reported syntheses include HIV-1 protease(1–50,Cys.amide), HIV-1 protease(53–99), and
the full length HIV-l protease(1–99).
Republished with the permission of Blackwell Publishing from International Journal of Peptide Protein Research, volume 40,
pp. 180–193, 1992.
A preliminary account of this work was presented at the 12th American Peptide Symposium, Cambridge, MA, July 16–21, 1991 (ref.
43).
Dedicated to Professor Bruce Merrifield on the occasion of his 70th birthday. 相似文献
9.
Małgorzata A. Broda Barbara Rzeszotarska 《International journal of peptide research and therapeutics》1998,5(5-6):441-443
Summary α,β-Dehydroamino acids are useful peptide modifiers. However, their stereoelectronic properties still remain insufficiently
recognized. Based on FTIR experiments in the range ofv
s(N-H), AI, AII andv
s(Cα=Cβ) and ab initio calculations with B3LYP/6–31G*, we studied the solution conformational preferences and the amide electron
density perturbation of Ac-ΔXaa-NHMe, where ΔXaa=ΔAla, (E)-ΔAbu, (Z)-ΔAbu, (Z)-ΔLeu, (Z)-ΔPhe and ΔVal. Each of these dehydroamides adopts a C5 structure, which in Ac-ΔAla-NHMe is fully extended and accompanied by the strong C5 hydrogen bond. Interaction with bond Cα=Cβ lessens the amidic resonance within the flanking amide groups. TheN-terminal C=O bond is noticeably shorter, both amide bonds are longer than the corresponding bonds in the saturated entities
and the N-terminal amide system is distorted. Ac-ΔAla-NHMe constitutes an exception. ItsC-terminal amide bond is shorter than the standard one and both amide systems are ideally planar. Ac-(E)-ΔAbu-NHMe shares stereoelectronic features with both Ac-ΔAla-NHMe and (Z)-dehydroamides. 相似文献
10.
The mean dimensions of thecis N-methyl peptide unit have been arrived at by analysing the crystal structure data on compounds containing such units. These
dimensions can be used as standard in conformational studies on cyclic peptides. While the bonds meeting at C are almost coplanar,
those meeting at N show a slight pyramidal disposition. A comparison of the dimensions of the normal and N-methylatedcis peptide units show that there are perceptible differences in the parameters connected with N. In addition, the flexibility
of thecis peptide unit has been analysed by studying the distribution of the parameters in different classes of compounds such as cyclic
di, tri and higher peptides. The salient features are: (i) The angle CαCN in cyclic dipeptide and the angle CδNCα in higher peptides tend to be lower, when the peptide unit is associated with a prolyl residue; (ii) in cyclic tripeptides
the internal anglesviz., CαCN and CNCα are significantly larger thereby increasing the intra-annular space; (iii) the bond Cα-C is distinctly shorter when it occurs in cyclic dipeptides. The results lead to the conclusion that thecis peptide unit takes up aneed-based flexibility in its dimension. 相似文献
11.
Summary. Chum salmon trypsin-catalyzed peptide synthesis has been studied by using nine series of "inverse substrates," i.e., p-amidinophenyl, p- and m-guanidinophenyl, p- and m-(guanidinomethyl)phenyl, and four position isomers of guanidinonaphthyl esters derived from N
α
-(tert-butyloxycarbonyl)amino acid as acyl donor components. They were found to couple with an acyl acceptor such as l-alanine p-nitroanilide to produce dipeptide in the presence of trypsin. All substrates tested in this study undergo less enantioselective
coupling reaction, and the coupling product was the favorably obtained d-series rather than l-series (in the present case; N
α
-Boc-d-Ala and N
α
-Boc-l-Ala). The optimum condition for the coupling reaction was studied by changing the organic solvent, buffer solution, pH, and
acyl acceptor concentration. It was found that the enzymatic hydrolysis of the resulting product was negligible.
Received August 10, 2000 Accepted December 2, 2000 相似文献
12.
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
13.
Eric Mossel Fernando Formaggio Giovanni Valle Marco Crisma Claudio Toniolo Mitsunobu Doi Toshimasa Ishida Quirinus B. Broxterman Johan Kamphuis 《International journal of peptide research and therapeutics》1998,5(2-3):223-225
Summary In order to obtain further information on the role played by phenyl ring position in the Cα-methylated α-amino acid side chain on peptide preferred conformation, the crystal-state structural preferences of Cα-methyl, Cα-phenylglycine peptides have been determined by X-ray diffraction. This study shows that either the fully extended conformation
or the β-bend/310-helical structures are adopted by peptides characterized by this Cα-methylated, β-branched, aromatic α-amino acid. 相似文献
14.
Casimir J. Richard Guichard Gilles Briand Jean-Paul 《International journal of peptide research and therapeutics》2001,8(2):89-93
Summary A rapid and one-pot synthesis of phthaloyl derivatives of α-amino carboxamides is described. In dichloromethane, α-amino carboxamides
react withmono-methylphthalate in the presence of BOP andi-Pr2NEt to afford the intermediateN
α-[(o-methoxycarbonyl)benzoyl]amino carboxamides which undergo cyclization in dichloromethane/water in the presence of aqueous
sodium hydroxide and tetrabutylammonium bromide catalyst to afford the correspondingN
α-phthaloyl amides in excellent yields. 相似文献
15.
L. A. Simeoni N. E. Byramova N. V. Bovin 《Russian Journal of Bioorganic Chemistry》2000,26(3):183-191
The first synthesis of the Neu5Gc analogue of SiaT
n
disaccharide, which can be detected in breast tumors by immunochemical methods, is reported. The regioselective sialylation
of (3-trifluoroacetamidopropyl)-2-azido-2-deoxy-α-D-galactopyranoside with peracetate of the methyl ester ofN-acetoxyacetyl-neuraminic acid β-ethylthioglycoside in the presence ofN-iodosuccinimide and trifluoromethanesulfonic acid (or its trimethylsilyl ester) resulted in the derivatives of α- and β-sialyl(2→6)galactosaminide
in 39 and 32% yields, respectively. The catalytic hydrogenolysis of the azido group and subsequentN- andO-acetylation of the α-anomer gave the peracetate of trifluoroacetamidopropyl glycoside. Removal of the protective groups led
to glycoside Neu5Gcα2→6GalNAcα-O(CH2)3NH2. Using the Neu5Gc derivative with acetoxyacetyl groups at positions O9 and O4 as a donor increases the α-selectivity of sialylation
to afford the α- and β-anomers in 69 and 8% yields, respectively. 相似文献
16.
A controlled growth chamber experiment was conducted to investigate the short-term water use and photosynthetic responses
of 30-d-old carrot seedlings to the combined effects of CO2 concentration (50–1 050 μmol mol−1) and moisture deficits (−5, −30, −55, and −70 kPa). The photosynthetic response data was fitted to a non-rectangular hyperbola
model. The estimated parameters were compared for effects of moisture deficit and elevated CO2 concentration (EC). The carboxylation efficiency (α) increased in response to mild moisture stress (−30 kPa) under EC when
compared to the unstressed control. However, moderate (−55 kPa) and extreme (−70 kPa) moisture deficits reduced α under EC.
Maximum net photosynthetic rate (P
Nmax) did not differ between mild water deficit and unstressed controls under EC. Moderate and extreme moisture deficits reduced
P
Nmax by nearly 85 % compared to controls. Dark respiration rate (R
D) showed no consistent response to moisture deficit. The CO2 compensation concentration (Γ) was 324 μmol mol−1 for −75 kPa and ranged 63–93 μmol mol−1 for other moisture regimes. Interaction between moisture deficit and EC was noticed for P
N, ratio of intercellular and ambient CO2 concentration (C
i/C
a), stomatal conductance (g
s
), and transpiration rate (E). P
N was maximum and C
i/C
a was minimum at −30 kPa moisture deficit and at C
a of 350 μmol mol−1. The g
s and E showed an inverse relationship at all moisture deficit regimes and EC. Water use efficiency (WUE) increased with moisture
deficit up to −55 kPa and declined thereafter. EC showed a positive influence towards sustaining P
N and increasing WUE only under mild moisture stress, and no beneficial effects of EC were noticed at moderate or extreme moisture
deficits. 相似文献
17.
Chemical synthesis of kurtoxin, a T-type calcium channel blocker 总被引:1,自引:0,他引:1
Hideki Nishio Yuji Nishiuchi Masanori Ishimaru Terutoshi Kimura 《International journal of peptide research and therapeutics》2003,10(5-6):589-596
Kurtoxin isolated from the venom of scorpion, Parabuthus transvaalicus, is a 63-residue peptide with four intramolecular disulfide bonds which inhibits low-threshold T-type Ca2+channels. Kurtoxin was synthesized by native chemical ligation involving the coupling of (1--26)-thioester peptide and Cys27-(28--63)-peptide. The former was synthesized by standard solid-phase peptide synthesis (SPPS) with Boc chemistry, while the
latter was sequentially assembled from three protected segments onto a resin-bound C-terminal segment in a chloroform--phenol
mixed solvent followed by deprotection reaction using HF. Each protected segment used for the coupling on a solid support
was prepared on an N-[9-(hydroxymethyl)-2-fluorenyl] succinamic acid (HMFS) resin and detached from the resin by treatment with 20% Et 3N in DMF to produce it in the form of an α-carboxylic acid. Synthetic kurtoxin obtained after the oxidative folding reaction was found to be identical with the natural
product by means of several analytical procedures, and its disulfide structure was determined for the first time to be Cys12-Cys61, Cys16-Cys37, Cys23-Cys44 and Cys27-Cys46 by peptide mapping, sequence analysis and mass measurements. 相似文献
18.
Summary. A procedure for the synthesis of enantiopure β3-amino acids from proteinogenic α-amino acids, developed by our group a few years ago, has been modified to enable the production
of C-2 fully deuterated, C-protected β3-amino acids and, even more important, the synthesis of valuable deuterium labelled N(Boc)-protected chiral synthons, such as 2-aminoalcohols, 2-aminoiodides, and β3-amino nitriles. 相似文献
19.
Romero PJ Romero EA Mateu D Hernández C Fernández I 《Cell biochemistry and biophysics》2006,46(3):265-276
Presence of subtypes of voltage-dependent Ca channels was investigated in young and old human red cells, employing immunological
and flux-kinetics methods. Western blots showed specific reaction toward polyclonal rabbit antibodies raised against a highly
conserved residue of α1C, subunit of high-voltage activated Ca channels (pan α1) and against conserved residues of α1C and α1E subunits. No specific reaction was detected with antibodies against conserved residues of α1A, α1B, or α1D subunits. Only a single band (approx 260 kDa) was revealed on anti-pan α1A or anti-α1E blots, whereas two bands (200 and 230 kDa) were detected by α1C exposure, Blots from old cells always showed diminished band intensity. Channel activity was assessed by studying the effect
of voltage-dependent Ca channels blockers' under conditions likely to alter the red cell membrane potential, through incubation
in media of different composition. In a 150 mM NaCl+5 mM KCl medium, blockers of L-, R-, and Q-type caused a 15–50% reductions of 45Ca influx into cells, which had the Ca pump inactivated by either exhaustive adenosine triphosphate depletion or presence
of vanadate plus substrates. Additionally, some P/Q-and N-type blockers also reduced Ca influx to various extents (25–60%).
Old cells were generally insensitive to L-type but not to non-L-type, blockers. Raising external K to about 70–80 mM reduced by 50–100% inhibition by L-type blockers. Incubation in a gluconate medium containing 150 mM Na+5 mM K practically abolished the action of L-type blockers, but only slightly reducing that by non-L-type. The results, clearly
demonstrate presence of L- and R-type Ca channels, apparently occurring in different functional states in young and old cells.
Other non-L-type channels were also demonstrated only by pharmacological means. A possible physiological role for these channels
is discussed. 相似文献
20.
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