太子参化学成分、药理作用和应用的研究进展

太子参Pseudostellariae Radix是中国传统补益中药材之一,兼具药用和食疗功效,主要含有挥发油、多糖、环肽、生物碱、皂苷、酚类等成分,具有降血糖、抗炎、抗癌、保护细胞、抑制酪氨酸酶、免疫调节等药理作用。对太子参的化学成分及其药理作用,以及太子参在临床、食疗、保健食品、化妆品、兽药制剂和功能性饲料添加剂等方面应用进行总结,为太子参进一步开发利用提供依据。     

雷公藤内生真菌中的环肽及其乙酰胆碱酯酶抑制活性

目的:内生菌作为一种良好的生物资源,已产生许多结构新颖、活性多样的代谢产物,在进行药用植物内生菌的研究中,分离得到了一株踝节菌属真菌,该属真菌是一个产多样代谢产物的真菌,从该内生菌中分离鉴定环肽类成分,并研究其乙酰胆碱酯酶抑制活性。方法:利用柱色谱法,包括硅胶柱色谱、大孔树脂柱色谱和小孔树脂(MCI)凝胶柱色谱等分离化合物;利用波谱方法,包括氢核磁共振、碳核磁共振、电喷雾质谱等鉴定化合物结构;采用改良的Ellman法测定化合物的乙酰胆碱酯酶抑制活性。结果:分离鉴定了4个环肽,它们分别鉴定为discarine-M(1), fumitremorgin C(2),fructigenine B(3), spirotryprostatin A(4),化合物1显示了中等强度的抗乙酰胆碱酯酶活性,其半抑制浓度(IC₅₀) 56 μmol·L^-1。结论:分离的4个化合物均为从踝节菌属(Talaromyces)真菌中首次分得。     

Molecular structures of two crystalline forms of the cyclic heptapeptide antibiotic ternatin,cyclo[-β-OH-d-Leu-d–Ile–(NMe)Ala (NMe)Leu-Leu-(NMe)Ala-d–(NMe)Ala-]

The crystal structures of two solvated forms of ternatin, cyclo[-β-OH-d -Leu-d -Ile-(NMe)Ala-(NMe)Leu-Leu-(NMe)Ala-d -(NMe)Ala-] are reported. The first crystallizes with two molecules of peptide and one of dioxane in the asymmetric unit: P2₁2₁2₁, a = 11.563(1), b = 21.863(2), c = 36.330(4) Å. The second crystallizes with two molecules of peptide and one of water in the asymmetric unit: P2₁2₁2₁, a = 14.067(2), b = 16.695(1), c = 36.824(6) Å. N-Methylation of four of the seven residues of ternatin appears to reduce the number of low-energy conformations the molecule can assume. The same H-bonded macrocyclic ring conformation is adopted by the backbone of each of the four molecules observed here. All the amino-acid side chains, with the exception of d -Ile², have similar orientations in each of the four conformers. The heptapeptide macrocycle is characterized by: (i) a cis peptide between (NMe)Ala³ and (NMe)Leu⁴, (ii) a type II β-bend, involving residues Leu⁵-(NMe)Ala⁶-d -(NMe)Ala⁷-β-OH-d -Leu², stabilized by two H-bonds, N1′05 and N5′01, between Leu⁵ and β-OH-d -Leu¹ residues, (iii) a third intramolecular H-bond, observed in each of the four molecules, between the hydroxyl group of β-OH-d -Leu¹ and the carbonyl oxygen of d -Ile².     

植物石竹型环肽的研究进展

植物环肽是一类结构新颖、生物活性很高的物质,石竹型环肽作为其重要的组成之一,在药物的开发利用及其疾病的治疗中扮演着重要的角色。本文从石竹型环肽的来源、生物活性以及生物合成途径三个方面对其进行了简要介绍,最后以太子参环肽为例,分析石竹型环肽在研究过程中存在的问题,并对植物环肽的的研究趋势进行展望,为相关研究提供参考。     

STEREOCHEMICAL STUDIES ON CYCLIC PEPTIDES

Conformational aspects of 4 → 1 hydrogen bonded cyclic pentapeptides are considered in this paper from the point of view of “contact criteria” and potential energy calculations. Three types of such hydrogen bonded conformations, designated A₁, A₂ and B, are possible, involving some amount of strain on the bond angles. The energy of hydrogen bonded cyclopentaglycyl is somewhat less than that of the five-fold symmetrical conformation. The stereochemical feasibility of introducing l - and d -alanyl residues in these structures has also been studied and the possible types for different sequences of alanyl residues have been determined. The results are discussed further in the light of the limited data available from crystal structure and nuclear magnetic resonance studies on cyclic pentapeptides.     

Primary Amine and Solvent‐Induced Polymerizations of L‐ or D,L‐Phenylalanine N‐Carboxyanhydride

Summary: Benzylamine, hexylamine and aniline‐initiated polymerizations of D ,L ‐phenylalanine and L ‐phenylalanine N‐carboxyanhydride (D ,L ‐Phe‐NCA and L ‐Phe‐NCA) were performed in various solvents. The isolated polypeptides were characterized by MALDI‐TOF mass spectroscopy. Exclusively linear polypeptides having one amide and one amino endgroup were found, when the polymerizations were conducted in a closed reaction vessel with dioxane or sulfolane as reaction media. Traces of water competed with aniline as initiator, when the reaction vessel was closed with a drying tube. In N,N‐dimethylformamide (DMF) formyl endgroups were formed at polymerization temperatures of 60 °C. In DMF and N‐methylpyrrolidone, cyclic oligo‐ and polypeptides were formed by a solvent‐induced polymerization initiated by zwitterions, which may compete with the primary amine‐initiated polymerizations.

MALDI‐TOF mass spectrum of a poly(D ,L ‐phenylalanine) polymerized in NMP without addition of an initiator.     

一些重要天然活性环肽化学和生物活性研究进展

天然环肽化合物以其广泛的分布、新奇的结构和丰富的活性成为化学家和药学家研究的热点。多年的天然产物化学及活性与药物研发已经从天然环肽化合物中发现一批药物, 包括免疫抑制剂环孢菌素A (cyclosporin-A, 1)、抗生素短杆菌肽S (gramicidin-S, 2)、万古霉素 (vancomycin, 3)、达托霉素 (daptomycin, 4) 等; 多个环肽化合物正在进行临床试验研究, 如具有抗肿瘤活性的海洋环肽aplidine (5) 等; 另有数个植物环肽化合物具有良好的成药前景, 如具有抗肿瘤活性的茜草科类型环肽RA-V (6) 和RA-VII (7)、免疫抑制活性的菊科类 型环肽astin-C (8) 等。本文将从分子及其重要活性发现、作用机制、构效关系或结构改造等方面简要介绍以上这些重要天然活性环肽的化学和生物活性研究进展, 期望帮助读者了解天然活性环肽化合物的研究概况。     

白僵蚕化学成分研究

目的研究白僵蚕Bombyx Batryticatus的化学成分。方法利用正相硅胶柱色谱、Sephadex LH20、反相硅胶柱色谱及反相制备液相色谱等手段进行分离纯化,并通过1H-、13C-NMR等波谱技术进行结构鉴定。结果从白僵蚕醋酸乙酯层中分离得到11个化合物,分别鉴定为环(D-脯-D-缬)二肽(1)、环(S-脯-R-亮)二肽(2)、环(D-脯-D-异亮)二肽(3)、环(D-脯-D-苯丙)二肽(4)、金色酰胺醇酯(5)、(+)-松脂醇(6)、异黑麦草内酯(7)、butyl-2-pyrrolidone-5-carboxylate(8)、(-)-杜仲树脂酚(9)、(-)-落叶松树脂醇(10)、4-羟基苯乙酸甲酯(11)。结论所有化合物均为首次从僵蚕中分离得到。     

中药两面针的化学成分及细胞毒活性成分研究

采用硅胶、凝胶、RP-18中压柱色谱、HPLC等分离方法,结合NMR,MS等波谱技术,从中药两面针的甲醇提取物中分离鉴定了10个化合物,分别为zanthonitidine B(1)、cyclo-(Leu-Leu-Leu-Leu-Ile)(2)、6S-10-O-demethylbocconoline(3)、鹅掌楸碱(liriodenine,4)、异阔果芸香碱(isoplatydesmine,5)、5,5′-二甲氧基落叶松脂醇(5, 5′-dimethoxylariciresinol,6)、丁香树脂醇(syringaresinol,7)、表丁香脂素(episyringaresinol,8)、异紫花前胡内酯(marmesin,9)、丁香醛(syringaldehyde,10)。其中化合物1为新的生物碱类化合物,化合物2为首次从植物界发现的环五肽,化合物3为首次从花椒属植物中分离得到的生物碱。化合物3和4对人结肠癌细胞HT29、人非小细胞肺癌细胞A549和人乳腺癌细胞MDA-MB-231均具有一定的细胞毒活性,其IC50分别为27.37, 24.10, 33.58μmol·L-1和9.12, 6.05, 11.35μmol·L^-1。     

Abbreviated nomenclature for cyclic and branched homo‐ and hetero‐detic peptides

Abstract: Amino acid sequences and linear or head‐to‐tail cyclopeptides can be represented conveniently in one‐line text formulae using the three‐letter symbols. However, other – but nonetheless important – topologies of peptides are ‘side chain‐to‐head (or tail)’, ‘backbone‐to‐backbone’, ‘side chain‐to‐side chain’ cyclopeptides, ‘side chain‐to‐side chain’ connected peptide strands, and branched peptides (like peptide dendrimers). In general, such structures cannot be described using the three‐letter symbols in one‐line text: a chemical structure editor is required for symbolic representations according to the IUPAC‐IUBMB recommendations. The aim of this contribution is to offer an unambiguous and general nomenclature system that enables researchers to represent all cyclic and branched homo‐ and hetero‐detic peptides in a coherent manner in one‐line text – as long as their as constituents can be represented in (three)‐letter codes. The application of this new nomenclature would overcome the existing difficulties and provide a way to express complex situations in the shortest way in order to highlight more clearly the salient points in a given scientific communication.