假单胞菌属合成环脂肽分子的研究进展

假单胞菌属合成的环脂肽是一类由脂肪酸和肽链组成、通过酯键成环、具有两亲性的分子。环脂肽有多种生理功能,除具表面活性外,还具有抗细菌、抗病毒、抗真菌、抑制肿瘤细胞等活性,可作为潜在的抗生素类药物被开发。本文就假单胞菌属所合成环脂肽的种类、功能和生物合成机制进行总结,同时对分子生物学、生物信息学等新兴学科技术结合传统分离鉴定技术在发现新型环脂肽类物质方面的运用作一综述。     

藻青菌环八肽Samoamide A的固相合成

以2-氯三苯甲基氯(CTC)树脂为固相载体,N,N′-二异丙基碳二亚胺(DIC)和1-羟基苯并三唑(HoBt)为缩合体系,通过9-芴甲氧羰基(Fmoc)固相合成法合成直链肽,然后将其从树脂上切下,以HoBt、苯并三唑-1-基氧三吡咯烷基六氟磷酸(PyBOP)和N,N′-二异丙基乙二胺(DIPEA)为环合试剂进行液相环合合成了广谱抗癌的藻青菌环八肽Samoamide A。将Samoamide A进行制备液相色谱纯化,采用MS、NMR等对其进行表征。结果表明,顺利得到纯度为99.12%的藻青菌环八肽Samoamide A,总收率为42.8%。该方法操作简便,收率高,适合于类似环肽的化学合成。目标化合物可作为筛选抗癌药物的先导化合物进行深入研究。     

大环三胺类化合物合成方法的研究进展

大环三胺类化合物是一类非常重要的化合物,但其合成比较困难,存在合成步骤多、产率低等问题。对大环三胺单体及其衍生物的合成方法进行了探讨,为大环三胺类化合物的相关研究提供了参考。     

环七肽PT-141的固相合成工艺研究

PT-141可有望作为治疗性功能障碍的环七肽药物。本文研究了固相合成法合成PT-141的路线及工艺,氨基酸的α-氨基采用9-芴甲氧羰基(Fmoc)保护,以HBTU/HOBT/NMM为肽合成试剂,用高压制备液相色谱对粗品进行纯化,用质谱仪对合成的多肽进行结构鉴定。多肽合成的收率可达58%,纯化后可得纯度为98%的目标环七肽。与文献方法相比,该法简便、环境友好,并大幅降低了合成成本,适合产业化生产。     

重氮化合物的合成方法

重氮化合物是重要的高活性有机合成中间体,可用来制备烯酮、环丙烷和三元杂环衍生物、环庚三烯衍生物、叶立德、金属卡宾、酮和偶氮类化合物等.因此,广泛应用于有机合成化学、药物合成化学和农用化学品的合成,其合成方法和应用也都得到了很大发展.目前合成重氮化合物的方法主要分为重氮转移法、其他官能团的重氮化法和重氮化合物的修饰法3种...     

6-硫-1,2,4-三氮-双环[3.2.0]庚烷-2,4-二烯的合成

以水合肼、硫氰酸盐、多聚甲醛为原料,经过五元环合成、氧化、四元环合成三步反应,合成6-硫-1,2,4-三氮双环[3.2.0]庚烷-2,4-二烯。对合成路线进行了条件优化。最高收率达61.8%。其结构经1H NMR确证。     

西仑吉肽的固相合成

采用Fmoc固相合成法,选用2-氯三苯甲基氯树脂作为固相载,HBTU/HOBt和HATU/HOBt为缩合剂,合成全保护线性肽.以V(DCM)∶V(THF)＝ 1∶1为溶剂,HATU/HOBt为缩合剂,合成全保护环肽.最后脱除保护基得终产物西仑吉肽.     

丁二烯调聚产物在合成香料中的应用

以丁二烯为起始原料，经加工合成1，5，9-环十二碳三烯，再进一步工加工，可得到环十二醇、环十二酮、环十二单烯等。以这些大环化合物为基础，可合成一系列有价值的合成香料。丁二烯调聚，可合成1，5，9-环十二碳三烯，该化合物进一步加工处理，可合成环十二酮、环十二醇、环十二单烯。从这些化合物出发，可合成各种大环化合物。按其香气特点来说，大致有麝香、木香、龙诞香，有个别化合物还有花香或混合香型，这些香型对香料工业有着十分重要的作用。随着我国石油化学工业的发展，展望未来，将给这些香料提供较为廉价的原料。一、产品一般…     

生物合成二酮哌嗪类化合物的环二肽合酶研究进展

环二肽合酶(CDPSs)是新发现的一类与非核糖体肽合成酶(NRPSs)不同的合成非核糖体肽的酶。该类酶以氨酰-tRNA(aa-tRNA)作为底物合成具有广泛生物活性的化合物——二酮哌嗪类化合物,CDPSs的催化机制比较特殊,只能利用20种天然氨基酸形成的氨酰-tRNA作底物,在后修饰酶的作用下形成环二肽类化合物。CDPSs的晶体结构与Ⅰ型氨基酸-tRNA合成酶(aa-tRSs)的催化结构域类似,但催化机制不同。CDPSs蛋白非常小,但与NRPSs一样,能催化完整的环二肽类化合物的合成。     

新型交联超支化聚烯烃的制备及表征

本本文采用丙烯酸羟乙酯与六氯环三磷腈反应合成三种化合物,丙烯酰氧乙氧基五甲氧基环三磷腈,二丙烯酰氧乙氧基四甲氧基环三磷腈和三丙烯酰氧乙氧基三甲氧基环二磷腈单体.并用红外对单体结构进行了表征.然后利用α-二业胺Pd催化剂通过链行走催化乙烯与合成的三种化合物共聚,制备了具有交联结构的新型超支化聚合物.对聚合物的交联度进行了...     

Synthesis of Short Peptides with Perfluoroalkyl Side Chains and Evaluation of Their Cellular Uptake Efficiency

With an increasing demand for macromolecular biotherapeutics, the issue of their poor cell-penetrating abilities requires viable and relevant solutions. Herein, we report tripeptides bearing an amino acid with a perfluoroalkyl (R_F) group adjacent to the α-carbon. R_F-containing tripeptides were synthesized and evaluated for their ability to transport a conjugated hydrophilic dye (Alexa Fluor 647) into the cells. R_F-containing tripeptides with the fluorophore showed high cellular uptake efficiency and none of them were cytotoxic. Interestingly, we demonstrated that the absolute configuration of perfluoroalkylated amino acids (R_F-AAs) affects not only nanoparticle formation but also the cell permeability of the tripeptides. These novel R_F-containing tripeptides are potentially useful as short and noncationic cell-penetrating peptides (CPPs).     

Sequence-Dependent Nanofiber Structures of Phenylalanine and Isoleucine Tripeptides

The molecular design of short peptides to achieve a tailor-made functional architecture has attracted attention during the past decade but remains challenging as a result of insufficient understanding of the relationship between peptide sequence and assembled supramolecular structures. We report a hybrid-resolution model to computationally explore the sequence–structure relationship of self-assembly for tripeptides containing only phenylalanine and isoleucine. We found that all these tripeptides have a tendency to assemble into nanofibers composed of laterally associated filaments. Molecular arrangements within the assemblies are diverse and vary depending on the sequences. This structural diversity originates from (1) distinct conformations of peptide building blocks that lead to different surface geometries of the filaments and (2) unique sidechain arrangements at the filament interfaces for each sequence. Many conformations are available for tripeptides in solution, but only an extended β-strand and another resembling a right-handed turn are observed in assemblies. It was found that the sequence dependence of these conformations and the packing of resulting filaments are determined by multiple competing noncovalent forces, with hydrophobic interactions involving Phe being particularly important. The sequence pattern for each type of assembly conformation and packing has been identified. These results highlight the importance of the interplay between conformation, molecular packing, and sequences for determining detailed nanostructures of peptides and provide a detailed insight to support a more precise design of peptide-based nanomaterials.     

二氧化碳与环氧烷加成反应的金属配合物催化剂及活化机理研究进展

综述了环氧烷与CO2开环加成反应合成环状碳酸酯的金属配合物催化剂的研究进展,讨论了金属配合物催化活化环氧烷和CO2完成环加成反应的活化机理,为CO2的化学利用及环氧烷合成环状碳酸酯工艺的研究、开发与应用提供参考。     

Computer-based de novo designs of tripeptides as novel neuraminidase inhibitors

The latest influenza A (H1N1) pandemic attracted worldwide attention and called for the urgent development of novel antiviral drugs. Here, seven tripeptides are designed and explored as neuraminidase (NA) inhibitors on the structural basis of known inhibitors. Their interactions with NA are studied and compared with each other, using flexible docking and molecular dynamics simulations. The various composed tripeptides have respective binding specificities and their interaction energies with NA decrease in the order of FRI > FRV > FRT > FHV > FRS > FRG > YRV (letters corresponding to amino acid code). The Arg and Phe portions of the tripeptides play important roles during the binding process: Arg has strong electrostatic interactions with the key residues Asp151, Glu119, Glu227 and Glu277, whereas Phe fits well in the hydrophobic cave within the NA active site. Owing to the introduction of hydrophobic property, the interaction energies of FRV and FRI are larger; in particular, FRI demonstrates the best binding quality and shows potential as a lead compound. In addition, the influence of the chemical states of the terminal amino acids are clarified: it is revealed that the charged states of the N-terminus (NH(3) (+)) and C-terminus (COO(-)) are crucial for the tripeptide inhibitory activities and longer peptides may not be appropriate. In addition, the medium inhibiting activity by acetylation of the N-terminus indicates the possible chemical modifications of FRI. Experimental efforts are expected in order to actualize the tripeptides as potent NA inhibitors in the near future.     

Synthesis and proinflammatory properties of muramyl tripeptides containing lysine and diaminopimelic acid moieties

The unusual amino acid diaminopimelic acid (DAP) was prepared by cross metathesis of appropriately protected vinyl glycine and allyl glycine derivatives. Catalytic hydrogenation of the cross-coupling product resulted in reduction of the double bond and the removal of protecting groups. The resulting compounds were appropriately protected for the polymer-supported and solution-phase synthesis of muramyl tripeptides 2 and 3, which differ in the amidation of the alpha-carboxylic acids of the isoglutamine and DAP moieties. Muramyl dipeptide (1, MDP), the DAP-containing muramyl tripeptide 3, and the lysine-containing muramyl tripeptides 4 and 5 induced TNF-alpha gene expression without TNF-alpha protein production in a human monocytic cell line. The observed block in translation could be removed by co-incubation with LPS, resulting in an apparent synergistic effect. Compound 2 did not induce TNF-alpha gene expression, neither did it exhibit a synergistic effect with LPS; this indicates that amidation of the alpha-carboxylic acids of the isoglutamine and DAP moieties results in a loss of biological activity. It is proposed that amidation of alpha-carboxylic acids is a strategy that may be used by pathogens to avoid detection by the innate immune system. Furthermore, the pattern recognition receptors Nod1 and Nod2 have been implicated in the possible induction of a synergistic effect of muropeptides with LPS.     

Supramolecular approach for synthesis and functionalization of cyclic macromolecules

This report highlights our recent findings concerning the synthesis of cyclic polymers based on supramolecular chemistry as well as the stereochemical recognition of helices by a cyclic macromolecule consisting of helical peptides and porphyrins. The first part will focus on an electrostatic self-assembly and covalent fixation strategy for the efficient synthesis of cyclic polymers. It has been shown that a unimeric polymer assembly is formed exclusively from the linear polymer precursor having cyclic ammonium salt end groups carrying dicarboxylate counter ions. An effective synthesis of cyclic polymers has been achieved by the subsequent covalent transformation of the ammonium salt groups. The process has been extended to the synthesis of cyclic macromonomers, which produced a unique polymer network having both covalent and mechanical linkages. The second part will focus on the stereochemical recognition of helices by a cyclic host. α-Aminoisobutyric acid (Aib) peptide-based cyclic hosts having metalloporphyrin units have been synthesized for guest binding and chiroptical sensing. By using these cavities, biologically important “peptide bundling” has been realized through complexation of helical peptide guests, where the three helical chains, two of which are from the host and one from the guest, are harmonized stereochemically in a confined cavity, leading to intense chiroptical outputs in the absorption bands of the metalloporphyrin units. The selective peptide bundling events based on helical senses of the host/guest molecules has also been achieved with a chiral conformational matching.     

Herstellung und Anwendungsmöglichkeiten von Cyclododecatrien und Cyclooctadien

Production and applications of cyclododecatriene and cyclooctadiene. Today the cyclic trimerization of 1,3-butadiene to cyclododecatriene and the synthesis of cyclododecatriene derivatives are accomplished on an industrial scale using fully developed processes. This paper surveys the variety of the derivatives and their applications. The cyclic dimerization of 1,3-butadiene to cyclooctadiene and the synthesis of cyclooctadiene derivatives have also been performed on a technical scale for some years now. The paper gives examples of these derivatives, including polyoctenamer a rubber whose properties are considered to be due to the presence of cyclic macromolecules.     

Branched aliphatic polyesters by ring-opening (co)polymerization

The rapid development of biodegradable and biocompatible materials for biomedical applications is reflected in the search for new methods for aliphatic polyester modification applicable in this field. One possible approach is modification by changes to the polymer topology.This review covers the main methods of synthesis of branched aliphatic biodegradable and biocompatible (co)polyesters, where the ring-opening polymerization (ROP) of cyclic esters or cyclic carbonates is the leading process. First, literature examples of ring-opening multibranching polymerization (ROMBP) of AB₂-type hydroxyl-substituted cyclic lactones, lactides and carbonates are cited followed by the presentation of the application of AB-type cyclic esters and additionally AB₂ cyclic ethers or esters as “branching monomers” for the synthesis of branched polyesters based on polycaprolactone (PCL), polylactide (PLA) and polyglycolide (PGA). In the following part, methods involving the combination of the ROP of AB-type cyclic esters and condensation processes leading to branched structures are summarized. Other related strategies leading to “dendri-star” or “core–shell” copolyesters are also discussed. Several examples of approaches to PCL and PLA graft copolymer syntheses are also shown. The advantages and disadvantages of the presented methodologies of branched polyester synthesis are highlighted. Finally, the influence of the branched structure on the properties of the presented class of polyesters, important from the application point of view, is considered.     

Examination of a Structural Model of Peptidomimicry by Cyclic Acyldepsipeptide Antibiotics in Their Interaction with the ClpP Peptidase

The cyclic acyldepsipeptide (ADEP) antibiotics act by binding the ClpP peptidase and dysregulating its activity. Their exocyclic N‐acylphenylalanine is thought to structurally mimic the ClpP‐binding, (I/L)GF tripeptide loop of the peptidase's accessory ATPases. We found that ADEP analogues with exocyclic N‐acyl tripeptides or dipeptides resembling the (I/L)GF motif were weak ClpP activators and had no bioactivity. In contrast, ADEP analogues possessing difluorophenylalanine N‐capped with methyl‐branched acyl groups—like the side chains of residues in the (I/L)GF motifs—were superior to the parent ADEP with respect to both ClpP activation and bioactivity. We contend that the ADEP's N‐acylphenylalanine moiety is not simply a stand‐in for the ATPases' (I/L)GF motif; it likely has physicochemical properties that are better suited for ClpP binding. Further, our finding that the methyl‐branching on the acyl group of the ADEPs improves activity opens new avenues for optimization.