环肽的合成研究进展

对环肽进行了分类, 并对具代表性的经典型、DKP (Diketopiperazine, 哌嗪二酮)型、醚桥型、烯桥型、单硫及多硫醚型、刚性桥型、仲(叔)胺型、Mannich碱型、联苯型及Freidinger型环肽的合成方法逐一进行了描述.     

环肽合成进展

环肽由于其稳定的结构特性在生物模拟、药物设计、纳米与分子器件、生物传感器以及催化剂等方面起着越来越重要的作用。本文介绍了近年来环肽化合物的合成及其应用的一些进展。     

微波促进催产素和赖氨加压素环肽的固相合成

以Rink Amide-MBHA树脂为载体, 采用Fmoc/tBu正交保护固相合成策略, 运用微波照射促进, 先快速高效地合成得到载有催产素或赖氨加压素还原型多肽的树脂, 再将连接在树脂上的各还原型多肽分别在微波促进条件下和常温条件下环合形成二硫键制得环肽, 最后用Reagent K试剂将环肽从树脂上裂解下来得到目标多肽的粗品. 利用HPLC法测定不同固相环合条件下得到的多肽粗品纯度, 结果显示经微波促进固相环合得到的多肽粗品纯度明显高于常温条件下得到的多肽粗品纯度. 粗品最后经过反相制备高效液相系统纯化并冻干得到目标多肽纯品, 通过电喷雾质谱法测定了制得的还原型多肽及相应环肽的分子量, 验证了它们的结构.     

二茂铁类环肽的合成与分子识别研究

设计并合成了两个系列含二茂铁单元的1+1型和2+2型类环肽,用循环伏安法研究了1+1型二茂铁类环肽与含氧负离子和卤素负离子的包合作用.结果表明,类环肽能很好地识别这些常见的负离子.¹HNMR研究发现,类环肽对负离子的识别作用主要是通过类环肽酰胺键中氢与客体负离子形成分子间氢键实现的.     

富含二硫键的小分子肽合成研究进展

综述了目前多肽合成领域构建2-3个二硫键的策略和对二硫键排列方式给予定位的方法。     

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.     

选择性氧化形成三对二硫键合成齐考诺肽

利用不同保护基保护的巯基的氧化反应性不同,分别以空气和碘作为氧化剂,通过选择性氧化工艺使齐考诺肽线性肽的1,8,16,20-位两对Trt保护巯基先形成两对二硫键,然后用碘氧化15,25-位Acm保护的巯基,成功地生成第三对二硫键,合成了齐考诺肽.     

环肽研究新进展

本文对近年来环肽的合成方法及环肽的性质和应用的新进展进行了评述。     

一种含两对密集二硫键的模拟肽

利用α-芋螺毒素的骨架(CC—C—C)及天然堂皇芋螺毒素的氨基酸组成,设计了一个由11个氨基酸组成的线性短肽NTLCCEGCMCY-COOH.该肽在缓冲溶液中氧化折叠后二硫键只形成一种连接方式[C(1)—C(4),C(2)—C(3)],区别于大部分的α-芋螺毒素的二硫键连接方式[C(1)—C(3),C(2)—C(4)],且该肽具有镇痛活性.这是目前合成的二硫键最密集的α-芋螺毒素样模拟肽,可作为药物分子设计的模板.     

含巯基/二硫键聚合物生物材料

含巯基/二硫键聚合物生物材料具有多种良好的性能,作为药物、基因等的释放载体在生物医学领域具有广泛的应用前景。随着基因工程和组织工程的发展,含巯基/二硫键聚合物生物材料的可生物降解性得到高度重视,而怎样改善其降解性能成为限制其应用的关键因素。由于二硫键在细胞外环境里保持稳定,在细胞溶质的还原环境中容易发生断裂,因此在制备新型基因、药物等释放载体上,二硫键充当了重要的角色,它的引入为聚合物生物材料的生物降解性能的设计与改善提供了一条重要的途径。本综述重点以聚合物水凝胶、聚合物微胶束、囊泡等为例,从巯基/烯的光聚合反应、Michael加成反应、氧化还原反应的角度,介绍了巯基/烯在聚合物中形成二硫键的不同途径的研究进展,并详细论述了基因载体、蛋白质载体、小分子药物载体三种还原敏感型材料的制备、表面修饰和改性的进展情况,进一步强调含巯基/二硫键聚合物生物材料的研究在生物医学领域应用的重要性。     

Mannich型环肽的液相及固相合成比较

为了改善肽化合物的抗酶解能力，首次介绍了3肽Pro-Pro-Tyr分子的非天然环 化反应，其中分别采用液相及固相两种合成方式组装直链肽，再经过分子内 Mannich缩合，得到以Mannich碱为桥连结构的环肽5（产率5.38%)及10（产率72. 7%)。产物结构经氨基酸组分及质谱分析证明。结果表明，固相法环合可以避免分 子间反应，因此产物收率明显高于液相法。     

An Efficient Synthesis of Cyclopeptides Bridged with Aliphatic-aryl Ether Bond

Based on the pseudo-dilution effect (PDE) on solid support, three cyclopeptides with an aliphatic-aryl ether bond as the bridge were synthesized via SN2 reaction between bromoacetylated at N-terminal and the phenol -OH group in C-terminal Tyr residue. All the products were obtained in good overall yields and characterized by related analytic data.     

Synthesis and Structure of a Novel Alkynyl-Containing Disulfide Compound as Cathode Materials for Secondary Lithium Batteries

A novel alkynyl-containing disulfide compound, 5,8-dihydro-1H,4H-2,3,6,7-tetrathia-anthracen (TMSEDTTA), was synthesized. The structures of the target compound and the intermediates have been identified by ¹H NMR, ¹³C NMR, mass spectrometry, Fourier-transform infrared, Raman spectra, x-ray photoelectron spectroscopy, and elemental analysis. In addition, the structure of (Z)-(1,2-dibromo-2-(2,3,5,6-tetrakis(bromomethyl)phenyl)vinyl)trimethylsilane (5) was determined by single x-ray analysis.

[Supplementary materials are available for this article. Go to the publisher's online edition of Synthetic Communications® for the following free supplemental resource(s): Full experimental and spectral details.]     

Chemical Synthesis of Interleukin‐2 and Disulfide Stabilizing Analogues

Chemical protein synthesis allows the construction of well‐defined structural variations and facilitates the development of deeper understanding of protein structure–function relationships and new protein engineering strategies. Herein, we report the chemical synthesis of interleukin‐2 (IL‐2) variants on a multimilligram scale and the formation of non‐natural disulfide mimetics that improve stability against reduction. The synthesis was accomplished by convergent KAHA ligations; the acidic conditions of KAHA ligation proved to be valuable for the solubilization of the hydrophobic segments of IL‐2. The bioactivity of the synthetic IL‐2 and its analogues were shown to be equipotent to recombinant IL‐2 and exhibit improved stability against reducing agents.     

A Diaminodiacid (DADA) Strategy for the Development of Disulfide Surrogate Peptides

Disulfide bond‐containing peptides are useful molecular scaffolds with diagnostic and therapeutic applications due to their good biological activity and good target selectivity, but their utility is sometimes limited by the lability of the disulfide moiety under reducing conditions and in the presence of disulfide bond isomerase. The development of disulfide surrogates with improved redox stability has been an area of ongoing research; and one possible strategy is based on a diaminodiacid (DADA) moiety, which can be used to synthesize the disulfide bond replacement peptides with precise structures and enhanced stability through automated solid‐phase peptide synthesis (SPPS). This review summarizes recent developments in the DADA‐based SPPS of peptide disulfide surrogates. Some representative applications and structural studies on the DADA‐based disulfide surrogates are described.     

室温合成二硫化二正丁基黄原酸酯及其表征

以正丁醇、氢氧化钠和二硫化碳为原料,水作溶剂合成正丁基黄原酸钠,再与一氯化硫反应,室温条件下合成对称的二硫化二正丁基黄原酸酯,并探讨了反应条件对合成正丁基黄原酸钠和二硫化二正丁基黄原酸酯产率的影响。通过红外(FT-IR)、核磁(1H NMR)、质谱(MS)及元素分析等技术手段确定了产物的结构。优化的合成条件为:n(正丁基黄原酸钠)∶n(S2Cl2)=2∶1.1,温度为室温,溶剂为THF,反应时间为2 min,产率可达83.2%,反应条件温和,反应迅速、收率高。     

二硫二茂铁的合成及其晶体结构

用AlI3作还原剂，还原二茂铁磺酰氯得到二硫二茂铁。通过元素分析，IR， ^1H NMR和^13C NMR对化合物进行了表征。用X射线单晶衍射法测定了该化合物的晶 体结构。结果表明，晶体属单斜晶系，P21空间群，a=0.61881（4）nm，b=0.3232 （9）nm，c=1.39056(11)nm，β=94.179（3）°，V=0.85593（12）nm^3，Dc=1. 628g/cm^3，μ=1.870mm^-1，F(000)=444，Z=2，R1=0.027，ωR2=0.0678。     

New Minor Cyclopeptides from Arenaria oreophila （Caryophyllaceae）

New minor cyclic peptides, named arenariphilin C 1 and arenariphilin D 2, were isolated from the whole plants of Arenaria oreophila (Caryophyllaceae). Their structures were determined as cyclo(Pro1-Pro2-Leu1-Leu2-Phe-Ser-Gly-Thr) and cyclo (Ser-Cys) on the basis of spectroscopic data, especially by two-dimension NMR (2D NMR) technologies.