瑞林类寡肽抗癌药物的合成研究进展

瑞林类药物是指以促性腺激素释放激素为母体的一类人工合成的寡肽类化合物,本文主要对瑞林类药物的液相合成、固相合成以及液-固联用合成进行综述。参考文献43篇。     

Optical resolution of racemic amino acid derivatives with molecularly imprinted membranes bearing oligopeptide tweezers

Molecularly imprinted polymeric membranes were prepared from various oligopeptide tweezers by the adoption of N‐α‐tert‐butoxycarbonyl‐D ‐tryptophan (Boc‐D ‐Trp) or N‐α‐tert‐butoxycarbonyl‐L ‐tryptophan (Boc‐L ‐Trp) as a print molecule. The chiral recognition ability of the formed molecular recognition sites was dependent on the absolute configuration of the print molecule adopted in the membrane preparation (molecular imprinting) process, whereas the candidate oligopeptide tweezers consisted of the L ‐amino acid residues. In other words, the membranes imprinted by the D ‐isomer recognized the D ‐isomer in preference to the corresponding L ‐isomer, and vice versa. The affinity constant between the target molecule and the chiral recognition site from the oligopeptide tweezers was higher than that from a single‐strand oligopeptide derivative. Those membranes selectively transported the enantiomer, which was preferentially incorporated into the membrane by dialysis. The permselectivities for these membranes exceeded their adsorption selectivities. © 2004 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 43: 385–396, 2005     

Peptide Modified Electrospun Glycopolymer Fibers

Oligo(Glu₇₀‐co‐Leu₃₀), a peptide synthesized by protease catalysis, is functionalized at the N‐terminus with a 4‐pentenoyl unit and grafted to polyLSL[6′Ac,6″Ac], a glycopolymer prepared by ring‐opening metathesis polymerization of lactonic sophorolipid diacetate. First, polyLSL[6'Ac,6”Ac] fiber mats are fabricated by electrospinning. Oxidation of the fiber mats and subsequent reaction with cysteamine lead to thiol‐functionalized fiber mats with no significant morphology changes. Grafting of the alkene‐modified oligopeptide to thiol‐functionalized polyLSL[6′Ac,6″Ac] fiber mats is achieved via “thiol‐ene” click reaction. X‐ray photoelectron spectroscopy analysis to characterize peptide grafting reveals that about 50 mol% of polyLSL[6′Ac,6′′Ac] repeat units at fiber surfaces are decorated with a peptide moiety, out of which about 1/3 of the oligo(Glu₇₀‐co‐Leu₃₀) units are physically adsorbed to polyLSL[6′Ac,6′′Ac]. The results of this work pave the way to precise engineering of polyLSL fiber mats that can be decorated with a potentially wide range of molecules that tailor surface chemistry and biological properties.

     

富硒大豆低聚肽口服液的制备及其主要成分分析

富硒大豆蛋白经过酶解、超滤、调配、杀菌等工艺,制备成富硒大豆低聚肽口服液,分析了产品中的硒含量、大豆低聚肽含量及氨基酸组成,其中硒含量2.45 mg/100 ml,大豆低聚肽含量(分子量1000 D以下)达到638.25 mg/100 ml,含有Se-Cys在内的19种氨基酸,研究结果为富硒大豆低聚肽产品的质量标准制定提供了一定的理论依据.     

吉林人参低聚肽的免疫调节作用

 为研究吉林人参低聚肽(GOP)对小鼠的免疫调节作用, 选取280 只SPF 级雌性BALB/c 小鼠, 随机分为7 组:空白对照组、乳清蛋白组(150 mg/kg)及5 个GOP 组(37.5、75、150、300、600 mg/kg)。连续灌胃30 d 后, 进行免疫7 项实验测定, 观察GOP 对小鼠免疫器官相对重量、细胞免疫功能、体液免疫功能、单核-巨噬细胞功能和NK 细胞活性的影响。结果表明:GOP 显著提高了ConA 诱导的小鼠脾淋巴细胞增殖能力、迟发型变态反应能力、抗体生成细胞数、小鼠碳廓清指数、巨噬细胞吞噬率和吞噬指数、NK 细胞活性(P<0.05), 且效果优于乳清蛋白。由此可知, GOP 可以通过增强细胞免疫功能、体液免疫功能、单核-巨噬细胞吞噬能力和NK 细胞活性, 起到增强免疫力的作用。     

Structure of liquid-crystalline phases formed by N-acetyl-L-glutamic acid oligomeric benzyl esters –2H NMR study

A series of N-acetyl-L-glutamic acid oligopeptide benzyl esters with exact residue numbers 4, 6, and 12 has been synthesized by a stepwise procedure. For these oligopeptide–dioxane binary systems, the behavior of the liquid-crystalline phases has been examined␣by the use of ²H NMR, and the results indicate that highly ordered aggregates formed by these oligopeptides in dioxane are in an alignment similar to that in a nematic mesophase. Received: 27 February 2001 Accepted: 8 May 2001     

海洋动物寡肽制备与功能特性研究进展

海洋动物中含有大量的活性肽,这些活性肽具有不同的功能特性。其中海洋动物寡肽具有抗氧化、抗肿瘤、抗菌、调节血糖、降低血脂、增强免疫力等重要的生物活性。对这些寡肽的结构,制备工艺,功能特性及其应用前景进行综述,为海洋药物和海洋功能食品的开发提供参考。     

Isolation and Identification of Antioxidative Peptide from Goose Liver Hydrolysate to Ameliorate Alcohol-Mediated Oxidative Stress Damage in HHL-5 Hepatocytes

The aim of this study was to isolate and identify antioxidative peptide from goose liver hydrolysate (GLHP) for ameliorating oxidative stress damage by alcohol in HHL-5 hepatocytes. In this research, the target antioxidative peptides in GLHP were separated, purified, and identified via a tangential flow ultrafiltration system combined with size exclusion chromatography (SEC), ion exchange chromatography (IEC), reversed-phase liquid chromatography (RP-LC), and LC-MS/MS. The results suggested that the amino acid sequence of the target antioxidative peptide for ameliorating alcohol-mediated oxidative stress damage in HHL-5 hepatocytes was Leu-Pro-Leu-Pro-Phe-Pro (LPLPFP), which had a molecular weight of 683.41 Da, and was derived from NADH-ubiquinone oxidoreductase chain 1 in goose liver. In addition, LPLPFP was confirmed to have a satisfactory stability and maintained high hepatic protective activity in a simulated gastrointestinal digestion. Moreover, the mechanism of LPLPFP prevented against oxidative stress damage in HHL-5 hepatocytes was attributed to inhibiting the production of reactive oxide species (ROS) by upregulating genes expression in the Ahr-NQO1 signal pathway. In conclusion, these results indicated that dietary GLHP supplementation could ameliorate alcohol-mediated oxidative stress damage and provide an affordable dietary intervention strategy to prevent alcohol-mediated hepatocyte damage.     

Tautomerization and Dissociation of Molecular Peptide Radical Cations

Radical‐mediated dissociations of peptide radical cations have intriguing unimolecular gas phase chemistry, with cleavages of almost every bond of the peptide backbone and amino acid side chains in a competitive and apparently “stochastic” manner. Challenges of unraveling mechanistic details are related to complex tautomerizations prior to dissociations. Recent conjunctions of experimental and theoretical investigations have revealed the existence of non‐interconvertible isobaric tautomers with a variety of radical‐site‐specific initial structures, generated from dissociative electron transfer of ternary metal‐ligand‐peptide complexes. Their reactivity is influenced by the tautomerization barriers, perturbing the nature, location, or number of radical and charge site(s), which also determine the energetics and dynamics of the subsequent radical‐mediated dissociatons. The competitive radical‐ and charge‐induced dissociations are extremely dependent on charge density. Charge sequesting can reduce the charge densities on the peptide backbone and hence enhance the flexibility of structural rearrangement. Analysing the structures of precursors, intermediates and products has led to the discovery of many novel radical migration prior to peptide backbone and/or side chain fragmentations. Upon these successes, scientists will be able to build peptide cationic analogues/tautomers having a variety of well‐defined radical sites.     

Concentration Dependent Transformation of Oligopeptide based Nanovesicles to Nanotubes and an Application of Nanovesicles

The concentration dependent transformation of an oligopeptide nanostructure from nanovesicles to nanotubes at neutral pH is presented. The oligopeptide Acp‐Tyr‐Glu (Acp: 6‐aminohexanoic acid) forms nanovesicles at a concentration of 6.9 mg mL^?1. At a concentration of 2.3 mg mL^?1 these vesicular structures completely disappear and nanotubular structures are observed. We have also successfully optimized an intermediate concentration (3.4 mg mL^?1) where an ordered array of fused vesicular structures are formed, which actually leads to the transition from nanovesicles to nanotubes. These vesicular structures are very much sensitive toward metal ions and pH. Biocompatible calcium ions and high pH (10.7) can trigger the rupturing of these nanovesicles. One important property of these nanovesicular structures is the encapsulation of a potent anticancer drug doxorubicin, which can also be released in the presence of calcium ions promising a future use of these nanovesicles as vehicles for carrying biologically important molecules.