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排序方式: 共有164条查询结果,搜索用时 93 毫秒
61.
《Journal of enzyme inhibition and medicinal chemistry》2013,28(6):385-398
AbstractEnzymatic cyclizations of squalene and oxidosqualene lead to sterols and other triterpenoids in bacteria, fungi, plants, and animals. The cyclases for these reactions catalyze formation and stabilization of polycyclic carbocations and direct the enzyme-specific, templated formation of new carbon-carbon bonds in regio- and stereochemically defined contexts. The development of mechanism-based irreversible inhibitors, photoactivatable inhibitors, and numerous substrate analogs have helped to unravel the stepwise events occurring in the catalytic sites of these enzymes by covalent modification of specific amino acid residues. 相似文献
62.
重组环状胸腺五肽结构类似物Cyclo-(Cys- Arg-Lys –Asp-Val-Tyr)的制备、鉴定和活性检测 总被引:1,自引:0,他引:1
为了实现蛋白内含肽(Intein)介导的重组环状胸腺五肽结构类似物[cyclo-(Cys -Arg-Lys –Asp-Val-Tyr),cTP]的高效制备,设计并合成编码6个氨基酸的cTP基因,克隆到表达载体pTWIN1,重组表达质粒pTW-cTp转化E.coli ER2566构建工程菌,IPTG诱导由几丁质结合域纯化标签(chitin binding domain,CBD)、2个蛋白内含肽和目的多肽组成的“多元”融合蛋白(CBD-intein1-cTP-intein2-CBD)的高效表达.几丁质柱亲合层析纯化融合蛋白后,改变pH值和温度诱导intein1 C端切割,硫醇MESNA诱导intein2 N端切割,释放N端为Cys,C端为硫酯的重组cTP线性前体,通过非保护多肽硫酯环合法实现环肽生成.激光飞行质谱结果显示,纯化产物的分子量为764.4,与环肽的理论值相符.免疫活性检测结果显示,环肽cTP较线性多肽TP-5具有更显著的促进巨噬细胞吞噬能力的活性(P<0.01)和促进B细胞抗体生成的活性(P<0.01). 相似文献
63.
On the origins of triterpenoid skeletal diversity 总被引:1,自引:0,他引:1
The triterpenoids are a large group of natural products derived from C(30) precursors. Nearly 200 different triterpene skeletons are known from natural sources or enzymatic reactions that are structurally consistent with being cyclization products of squalene, oxidosqualene, or bis-oxidosqualene. This review categorizes each of these structures and provides mechanisms for their formation. 相似文献
64.
65.
Mycobacterium marinum produces carotenoids when exposed to light or when antimycin A is added. Although the major pigment synthesized is β-carotene, lycopene is accumulated when the induced bacteria are incubated in the presence of nicotine (5 mM) or 2-(4-chlorophenylthio)-triethylamine hydrochloride (CPTA) (50 μM). Both of these compounds inhibit β-carotene synthesis by blocking the cyclization of lycopene. When nicotine is removed by washing the cells, the accumulated lycopene is cyclized to form β-carotene. The cyclization of lycopene is not an energy-requiring reaction and, furthermore, does not require oxygen or any other electron acceptor. Chloramphenicol addition also does not inhibit the conversion of lycopene to β-carotene indicating that no de novo protein synthesis is involved. Nicotine appears to act by inhibiting the activity of the enzyme required for the cyclization of lycopene.Although the mode of action of CPTA is similar to nicotine, it cannot be removed by washing once the cells have been incubated in its presence, suggesting that the molecule is tightly bound to the enzyme. The possible active molecular sites of nicotine and CPTA are discussed. 相似文献
66.
Two monoterpene synthases, (-)-pinene synthase and (-)-camphene synthase, from grand fir (Abies grandis) produce different product mixtures despite having highly homologous amino acid sequences and, presumably, very similar three-dimensional structures. The major product of (-)-camphene synthase, (-)-camphene, and the major products of (-)-pinene synthase, (-)-alpha-pinene, and (-)-beta-pinene, arise through distinct mechanistic variations of the electrophilic reaction cascade that is common to terpenoid synthases. Structural modeling followed by directed mutagenesis in (-)-pinene synthase was used to replace selected amino acid residues with the corresponding residues from (-)-camphene synthase in an effort to identify the amino acids responsible for the catalytic differences. This approach produced an enzyme in which more than half of the product was channeled through an alternative pathway. It was also shown that several (-)-pinene synthase to (-)-camphene synthase amino acid substitutions were necessary before catalysis was significantly altered. The data support a model in which the collective action of many key amino acids, located both in and distant from the active site pocket, regulate the course of the electrophilic reaction cascade. 相似文献
67.
68.
Williams NK Liepinsh E Watt SJ Prosselkov P Matthews JM Attard P Beck JL Dixon NE Otting G 《Journal of molecular biology》2005,346(4):1095-1108
A mutant version of the N-terminal domain of Escherichia coli DnaB helicase was used as a model system to assess the stabilization against unfolding gained by covalent cyclization. Cyclization was achieved in vivo by formation of an amide bond between the N and C termini with the help of a split mini-intein. Linear and circular proteins were constructed to be identical in amino acid sequence. Mutagenesis of Phe102 to Glu rendered the protein monomeric even at high concentration. A difference in free energy of unfolding, DeltaDeltaG, between circular and linear protein of 2.3(+/-0.5) kcal mol(-1) was measured at 10 degrees C by circular dichroism. A theoretical estimate of the difference in conformational entropy of linear and circular random chains in a three-dimensional cubic lattice model predicted DeltaDeltaG=2.3 kcal mol(-1), suggesting that stabilization by protein cyclization is driven by the reduced conformational entropy of the unfolded state. Amide-proton exchange rates measured by NMR spectroscopy and mass spectrometry showed a uniform, approximately tenfold decrease of the exchange rates of the most slowly exchanging amide protons, demonstrating that cyclization globally decreases the unfolding rate of the protein. The amide proton exchange was found to follow EX1 kinetics at near-neutral pH, in agreement with an unusually slow refolding rate of less than 4 min(-1) measured by stopped-flow circular dichroism. The linear and circular proteins differed more in their unfolding than in their folding rates. Global unfolding of the N-terminal domain of E.coli DnaB is thus promoted strongly by spatial separation of the N and C termini, whereas their proximity is much less important for folding. 相似文献
69.
George ?sapay Giuseppe Melacini Qin Zhu Lida Tehrani Murray Goodman 《Letters in Peptide Science》1994,1(2):81-87
Summary The synthesis of the lanthionine analog of somatostatin[1–14] on a Kaiser-oxime resin is described. The 12-residue peptide segment [3–14] was assembled and cyclized on the resin by using the method of peptide cyclization on an oxime resin (PCOR); the product was obtained with good yield (41%) and purity (94%). The Fmoc protecting group on the N-terminus was cleaved with DBU, followed by a 2+12 segment condensation in solution. The chromatographic (HPLC, CZE) and spectral (UV, NMR) properties of the lanthionine and the natural somatostatins have been studied and compared. Preliminary biological tests show that the lanthionine and the natural somatostatins exhibit similar binding affinities to somatostatin receptor SSTR2.Abbreviations AlaL
one end of a lanthionine unit
- Boc
tert-butyloxycarbonyl
- BOP
benzotriazol-l-yl-oxy-tris-(dimethylamino)-phosphonium hexafluorophosphate
- Bzl
benzyl
- Cbz
benzyloxycarbonyl
- DQF-COSY
double-quantum-filtered correlated NMR spectroscopy
- CZE
capillary zone electrophoresis
- DBU
1,8-diazabicyclo[5.4.0]undec-7-ene
- DCC
N,N-dicyclohexylcarbodiimide
- DCM
dichloromethane
- DIEA
N,N-diisopropylethylamine
- DMF
N,N-dimethylformamide
- DMSO-d6
hexadeuterated dimethylsulfoxide
- EDC
1-ethyl-3-(3-dimethylaminopropyl)carbodiimide
- Fmoc
9-florenylmethoxycarbonyl
- For
formyl
- HMPA
hexamethylphosphoramide
- HOBt
N-hydroxybenzotriazole
- HOHAHA
homonuclear Hartmann-Hahn experiment
- HPLC
high-performance liquid chromatography
- ROESY
rotating frame nuclear Overhauser enhancement spectroscopy
- TFA
trifluoroacetic acid
- PCOR
peptide cyclization on an oxime resin
- Tmac2O
trimethylacetic or pivalic anhydride
- Tos
p-toluenesulfonyl 相似文献
70.
Work was undertaken to examine methodology for the cyclization of linear tripeptides on the solid phase via intramolecular S-alkylation using the Multipin(trade mark) Solid-Phase Peptide Synthesis platform. While previous work had shown that this chemistry could be used to efficiently cyclize linear tetrapeptide libraries, application of this synthetic strategy to the model linear tripeptide sequence Leu-Ser-Lys resulted in significant cyclic dimer formation. Ultimately, it was found that the addition of a large excess of lithium in the form of LiCl to the cyclization solution, significantly reduced cyclic dimer formation affording highly pure crude cyclic monomer. The application of this modified cyclization protocol to the preparation of cyclic peptide libraries was successfully demonstrated with the synthesis of a 20-membered library 4{1-20} based on the linear tripeptide sequence Leu-Xxx-Lys in which the position Xxx was varied with the standard 20 proteogenic residues. 相似文献