提高接肽缩合率的研究进展

本文针对多肽合成中缩合反应存在"困难肽段"的情况, 反析了影响缩合率的原因,归纳了改善缩合率的措施。 它们对提高经典液相法及固相法肽合成的质量均有实际意义。     

TTT活泼酰胺法在固相肽合成中的应用——促生长激素释放肽的合成及其生物活性

通过合成促生长激素释放肽,对四氢噻唑-2-硫酮(TTT)活泼酰胺法在固相肽合成中的应用进行了研究。实验结果表明,TTT活泼酰胺同载体上的氨基组分的缩合反应速度很大,每步缩合反应的产率很高(>99.3％),最终产品的纯度也很令人满意。此外,还报道了合成肽的生物活性。     

天冬酰胺的环化缩合反应及其在合成拮抗剂与吗啡肽中的应用

天冬酰胺的环化缩合反应及其在合成拮抗剂与吗啡肽中的应用;四氢嘧啶酮;构象;内源性吗啡肽     

环肽合成方法的研究进展

介绍了纯环肽与杂环肽合成的方法、策略及其优缺点,列举了一些常用缩合试剂,探讨了反应溶液浓度、线型肽前体化合物的结构及构象等因素对环化反应的影响.     

酶促合成肽的研究 II: 含羧基侧链氨基酸的肽的酶促合成

用嗜热菌酶酶促合成了一系列含门冬氨酸、谷氨酸的肽. 实验证明, 缩合反应中羧基组份中的门冬氨酸β-羧基或谷氨酸γ-羧基毋需保护. 同时也研究了邻近氨基酸残基对缩合反应的影响.     

酶促合成肽的研究 Ⅱ.含羧基侧链氨基酸的肽的酶促合成

用嗜热菌酶酶促合成了一系列含门冬氨酸、谷氨酸的肽。实验证明,缩合反应中羧基组份中的门冬氨酸β-羧基或谷氨酸γ-羧基毋需保护。同时也研究了邻近氨基酸残基对缩合反应的影响。     

四组份缩合反应(Ugi反应)

异腈是一个十分活泼的亲核成份。它与酸、胺、醛在Mannich反应条件下能生成具有肽骨架的缩合产物,称为四组份缩合。有二类四组份缩合,图1所表示的反应称为四组份缩合肤片断偶合,简写为4CC卜SC.图2所表示的反应称为四组份缩合立体选择性肤片断合成,简写为4CC一555。后者之不同于前者在于在产物分子中新生成了一个不对称的碳原子.     

微波作用下大位阻氨基酸与H-Pro-CTC树脂的高效缩合

微波反应下, 运用新型固相肽合成反应器, 深入研究了五种大位阻氨基酸与H-Pro-CTC树脂(CTC树脂, 2-氯三苯甲基氯树脂)的缩合反应. 使用三次缩合的策略, 分别在DMF/NMP/THF (V∶V∶V＝1∶1∶1), NMP/DMSO/THF (V∶V∶V＝4∶1∶1), DMF/DMSO/THF (V∶V∶V＝4∶1∶1)混合溶剂中缩合一次, 每次缩合反应的最优条件为: 缩合试剂HBTU、氨基酸浓度7 mmol/L、微波辐射3 min、反应温度35 ℃、维持时间3 min, 与传统方法相比, 氨基酸的用量大大减少, 其过量倍数从5倍降低为2倍, 缩合反应速率提高了16倍以上. 五种大位阻氨基酸与H-Pro-CTC树脂的缩合率都提高到80%以上.     

碳酸酯把手改构Wang树脂及其性能

基于碳酸酯结构易于亲核脱除的原理, 使用氯甲酸氯甲酯改构Wang树脂, 并探究了改构树脂与首位氨基酸的缩合效率. 实验结果表明, 改构后的Wang树脂与20种Fmoc保护氨基酸均能达到70%以上的缩合效率; 且对于带有较大侧链基团的Fmoc保护氨基酸, 通过降低树脂取代度或延长反应时间可提高其连接率. 为了验证改构后的碳酸酯型树脂在裂解时侧链未受到影响, 设计合成了3种模型肽, 并用温和裂解剂3-吡啶甲醛肟铯盐进行裂解. 实验结果表明, 利用改构树脂能得到侧链全保护的肽片段, 可初步应用到长链困难肽的合成中.     

壳聚糖缩合呋喃甲醛螯合树脂的合成及性能研究

利用壳聚糖C2 位上活泼氨基与呋喃甲醛缩合反应 ,合成了一种新型树脂。通过L9(34 )正交试验 ,研究了缩合反应的最佳条件 :80℃乙醇中溶胀 1h ,反应 5h ,pH =4.0～ 4.5 ,反应物配比 (氨基摩尔∶醛基摩尔 )为 1∶4,缩合率达到 90 %以上。并测定了上述螯合树脂对过渡金属离子的吸附性能。     

Conformation Analysis of Ile-Ala-Val-Pro Peptide and Its Derivatives by Circular Dichroism

Ile-Ala-Val-Pro as a hypocholesterolemic peptide was isolated from soybean protein. We have synthesized four peptides, Ile-Ala-Val-Pro-Gly-Glu-Val-Ala, Leu-Ile-Ala-Val-Pro-Gly-Glu-Val-Ala, Ile-Ala-Val-Pro-Thr-Gly-Val-Ala, Leu-Ile-Ala-Val-Pro-Thr-Gly-Val-Ala, with a conserved Ile-Ala-Val-Pro amino acid sequence, for circular dichroism investigations. These four peptide sequences were also found in the amino acid sequence in soybean protein, which was defined from the genomic sequence. Additionally for a detailed analysis of conformation features of these peptides, the Ile-Ala-Val-Pro and Leu-Ile-Ala-Val-Pro were also synthesized. All peptides were prepared using standard fluorenylmethyloxycarbonyl methodology and the peptide yields ranged from 90 to 95% of the theoretical yields with purity after purification above 99%.     

A mild high yielding synthesis of oxazole-4-carboxylate derivatives

Several 2,5-disubstituted oxazole-4-carboxylates were prepared in high yields from the methyl esters of N-acyl-β-halodehydroaminobutyric acid derivatives by treatment with a 2% solution of DBU in acetonitrile. The scope of this reaction was investigated and it was found that dehydrodipeptides having a β-bromodehydroaminobutyric acid residue gave the corresponding oxazoles in good yields. The photophysical properties of some of the oxazoles prepared were studied in four solvents of different polarity. All compounds have reasonable high fluorescence quantum yields and a moderate solvent sensitivity, which makes them good candidates to be used as fluorescent probes. One of the fluorescent oxazoles prepared was inserted after cleavage of the methyl ester into two model peptides using a conventional solution phase strategy. The photophysical properties of the labelled peptides were studied in ethanol and water and compared with those of the oxazole. The results obtained showed that the oxazole maintains a good fluorescence level and the same solvent sensitivity when linked to a peptide chain.     

酸敏性PEG载体的合成及其在多肽合成中的应用

本文通过聚苯乙烯固载聚乙二醇氨基树脂与羟甲基苯氧乙酸缩合制备了具有酸敏手臂结构的对羟甲基苯氧乙酰胺ＰＥＧ树脂。在合成中改进了ＰＳ－ＰＥＧＮＨ２树脂的制备方法,提高了树脂上功能基的转化率,不必进行封闭剩余活性基的操作,就得到具有单一功能基的树脂。     

Synthesis and characterization of novel fluorescent N-glycoconjugates

Novel fluorescent N-glycoconjugates containing d-glucose, glycine and coumarin or naphthalenetriazole derivatives were prepared by peptide synthesis type methods. The fluorescence properties (spectra, quantum yields) of the compounds were evaluated.     

Solid-phase synthesis of peptide ribonucleic acids (PRNA)

The range of available peptide ribonucleic acid (PRNA) monomers was fully expanded for the use in solid-phase synthesis of PRNA oligomers, which were designed to reversibly control the recognition and complexation behavior of the complementary DNA/RNA by external factors. A couple of PRNA 12-mers with desired purine-pyrimidine mixed sequences were prepared indeed in high yields by the solid-phase synthesis.     

Facile formation of chiral calixarene analogs incorporating cystine peptide into the macrocyclic ring

Chiral calixarene analogs incorporating cystine peptide into their macrocyclic ring were easily prepared by the cyclization reactions of bis(chloromethyl)phenol-formaldehyde oligomers with cystine peptides in moderate yields. Circular dichroism (CD) spectra indicated the existence of the transmission of the chirality from peptide unit to phenol-formaldehyde oligomer moiety.     

Synthesis of cross-linked polystyrene-supported polyethylene glycol and investigation of its property in peptide synthesis

The polyethylene glycol resin (PEG-Resin) which possesses hydrophilic properties was prepared by grafting the polyethylene glycol onto the chloromethylated copolymer of styrene and divinylbenzene in the presence of concentrated sodium hydroxide solution. The proceeding of the graft reaction was identified by IR spectrum analysis. There factors which affected the grafting reactions were investigated. By using the PEG-Resin polymer support, we compared the reactions for the syntheses of a tetra-peptide and a penta-peptide with the Merrifield solid peptide synthesis. We also measured the reaction kinetics of these reactions. The experimental results showed that by employing the PEG-Resin, the reaction rates and condensation yields of these peptide syntheses were improved.     

Solid-phase staudinger ligation from a novel core-shell-type resin: a tool for facile condensation of small peptide fragments

[reaction: see text] Solid-phase Staudinger ligation of small peptides was performed on a novel core-shell-type resin. Solid-phase Staudinger ligation was mediated by synthetic solid-supported phosphinothiol, which was readily prepared by a straightforward synthetic route. This protocol afforded final peptide products in excellent yields and purities and thus could provide the opportunity to facilitate a simple manipulation for condensation of peptide fragments. In particular, the resulting resin could be recycled in a successful manner.     

Synthesis and hydrolytic stability of novel 3-[F]fluoroethoxybis(1-methylethyl)silyl]propanamine-based prosthetic groups

Two new silicon-based prosthetic groups, derived from 3-[ethoxybis(1-methylethyl)silyl]propanamine, have been prepared in good yields. These silicon groups bearing an acid or an azide group were coupled to a model tripeptide (Leu-Gly-Gly) either through a classical amide bond formation or through “click chemistry” via the Huisgen cycloaddition. The radiolabelling with fluorine-18 by substitution of the ethoxy group at silicon has been carried out with success in 51-54% decay corrected radiochemical yields. Radiolabelled peptides were easily prepared by direct ¹⁸F-fluorination of the silicon-bearing tripeptide or by coupling the peptide with a radiolabelled silicon-based prosthetic group. Their stabilities in physiological medium were studied and proved poor.     

Selenomethionine Extraction from Selenized Yeast: an LC-MS Study of the Acid Hydrolysis of a Synthetic Selenopeptide

A synthetically prepared seleno-peptide (AHPDVLTVXLQMLDDGR) was used as a model system for the acid hydrolysis of selenized yeast proteins. The seleno-peptide is a tryptic peptide of a heat shock protein 104 from Saccharomyces cerevisiae, was subjected to acid hydrolysis using methanesulfonic acid over a time period of 8 hours. Aliquots of the solution were sub-sampled at predetermined time intervals and the peptide fragments characterized by reversed phase LC MSⁿ. Similarly, the appearance of amino acid residues in the solution was monitored. It was found that after about 8 hours the synthetic peptide completely hydrolyzed. The use of a selenopeptide as a model for hydrolysis of selenized yeast hydrolysis was validated by comparing the decomposition time profile of the synthetic peptide with that of a selenized yeast sample. The rate of hydrolysis was identical in both systems, suggesting that the employed acid hydrolysis yields to the complete decomposition of the Se containing proteins in yeast and consequently to the liberation of selenomethionine.