由D型氨基酸设计自组装短肽D-EAK16构建新型三维纳米纤维支架材料

采用D型氨基酸设计自组装短肽D-EAK16, 运用圆二色仪及原子力显微镜等仪器和细胞三维培养, 发现短肽D-EAK16在30 ℃时具有稳定的二级结构β-sheet, 在一定浓度下D-EAK16可形成由纳米纤维构成的透明水凝胶, 含水量高达99％, 可在细胞培养基(如PBS, DMEM)中形成支架. 细胞三维培养显示, 该水凝胶对细胞HO-8910和SPC-A-1的生长未见毒性. 比较D型氨基酸纳米支架和L型氨基酸纳米支架, 细胞的毒性未发现显著性差异. 采用D型氨基酸构建的自组装短肽, 可提供一个三维基质培养系统, 期望能广泛应用于生物医学工程等领域.     

自组装短肽作为“实时监控”纳米材料的初步研究

本文主要采用圆二色谱仪、原子力显微镜、刚果红染色等来探究手性自组装短肽GFS-15的二级结构、纳米形态和宏观形貌特征;通过循环伏安曲线、圆二色谱来检测浓度、时间、盐离子对它自组装过程的影响。结果表明,GFS-15能形成纳米纤维,能和金电极结合且影响其电化学行为,还可以作为细胞的三维培养基质材料;细胞三维培养常规实验以及细胞三维培养实时监控实验表明,细胞可在该肽形成的纳米三维微环境中生长,也能组装在金电极传感器的(纳米金)表面。本研究将为生物实时监控以及纳米生物医学的前沿研究打下基础。     

楔形短肽表面活性剂A3V3D纳米自组装结构的表征及机理研究

通过对传统短肽表面活性剂氨基酸序列的改良, 设计了具有楔形几何结构的新型短肽表面活性剂A3V3D. 圆二色谱(CD)分析表明, 该短肽的二级结构为无规则卷曲, 透射电子显微镜(TEM)和原子力显微镜(AFM)表征发现, 该短肽在水溶液中能够发生有序的自组装, 形成稳定的光滑平直的纳米纤维. 芘探针荧光光谱分析显示, 该短肽形成了疏水区并将芘分子包裹其中. 由此推测A3V3D在其楔形几何结构的影响下, 以柱状胶束的形式发生自组装, 是一种新型的自组装短肽材料, 说明了几何形状效应在控制短肽的自组装行为中起着关键作用.     

刺激响应型肽自组装及其应用

肽自组装体由于具有结构稳定、易调控、生物相容性好、可生物降解等优点,在构筑新型材料及生物医药领域表现出了巨大潜力。本文介绍了肽自组装的概念、机理和应用,详细归纳了刺激响应型肽自组装的研究进展;按照刺激源的不同将刺激响应型肽自组装分为pH响应型肽自组装、温度响应型肽自组装、溶剂响应型肽自组装、光响应型肽自组装、超声波响应型肽自组装以及离子响应型肽自组装;列举了肽自组装在药物控释、脊髓损伤修复、仿酶催化、生物模板等领域的应用。最后,基于目前肽自组装存在的一些问题(如影响肽自组装结构的外界因素不易精准把控、自组装的研究与生命科学领域的交叉程度低等)对肽自组装的发展做了展望。     

短肽自组装水凝胶的温和制备方法及免疫佐剂应用

短肽自组装水凝胶是一种新型的软物质材料,它由短肽通过自组装形成,具有生物活性和生物相容性高、易于设计与合成以及对外部刺激能快速响应等优点,它在生物医药、分析检测、组织工程等领域有很高的应用前景.本文主要总结了我们近年来在短肽自组装水凝胶温和制备方法研发方面的工作,同时介绍了短肽自组装水凝胶在疫苗佐剂方面的创新应用,并探讨了短肽自组装水凝胶研究领域的挑战及研究热点.     

二苯丙氨酸二肽微纳米结构的可控组装及应用

近年来,生物组装单元构筑微纳米结构的组装体在生物纳米技术等领域得到了广泛的研究。不同形貌的微纳米组装体可以通过生物分子的自组装这样快速、简便的方法获得。在众多肽基构筑基元中,二苯丙氨酸二肽及其衍生物作为一种生物活性的肽,具有生物兼容性好、容易化学修饰/生物功能化、制备简单等特点,是构筑微纳米结构材料时重要的生物基元之一。通过可控的方法组装,可以得到基于二苯丙氨酸及其衍生物的不同结构的组装体,他们在光学、机械工程、电化学传感检测等方面也具有广阔的应用前景。研究证明通过改变组装条件以及引入外源小分子等方法可以实现调控短肽的分子组装。本文综述了二苯丙氨酸二肽微纳米组装体的可控组装及他们在生物医学、生物传感、光电材料、光波导和催化等方面的应用。     

两亲性聚(L-谷氨酸γ-苄基酯)-聚乙二醇接枝共聚物的自组装行为和载药性能研究

由氨基酸及其衍生物聚合形成的聚肽,因其独特的结构和性能,近年来在蛋白质结构模拟、分子链构象研究、生物医学等领域备受关注．其中两亲性聚肽共聚物的自组装行为,为开发具有生物相容性、可控释、可降解性的新型药物载体创造了条件．目前对聚肽共聚物自组装及载药性能研究主要集中于聚肽嵌段共聚物胶束,     

温度对设计肽稳定性及自组装性能的影响

作为目前热门的研究领域,新型设计肽因具备优良的自组装性能及广泛的潜在应用而备受关注,但该类肽的热稳定性却一直未见相关报道。本文采用原子力显微镜(AFM)、圆二色(CD)对新型设计肽AC-Pro-SerPhe-Cys-Phe-Lys-Phe-Glu-Pro-NH2的热稳定性进行了研究。圆二色结果表明,设计肽的圆二色强度随着温度的升高而降低,到80℃谱图转变为典型的无规卷曲。二级结构含量分析发现,随着温度升高,β-转角和规则α-螺旋结构含量明显降低,而无规卷曲和不规则α-螺旋结构含量增加。实验发现肽溶液温度由90℃回复到室温后,设计肽的二级结构在30min内能够恢复。AFM结果显示,在低于80℃时,温度的升高不影响设计肽的自组装形成纤维结构。温度高于80℃时,设计肽形成不规则聚集体。但当温度回复到室温时,设计肽自组装纤维形貌自行恢复。研究表明该类设计肽具有优良的耐热性及快速的自我修复能力。     

肽超分子自组装:结构调控和功能化

生物分子自组装对生物体有重要意义,利用生物分子构筑具有功能性的有序组装体一直是人们关注的焦点.肽分子是一类重要的组装基元,肽的超分子自组装可形成多种纳米或微米尺度的结构,并可应用于能源、医药等领域.如何实现肽自组装结构的精准调控以及精准调控肽自组装实现功能化,是目前该领域面临的新挑战.肽的自组装是基于非共价键力的协同作用实现的,通过各种因素调节这些非共价键力的作用,是实现自组装结构调控和功能化的关键.虽然自组装结构调控可以通过改变外部环境调控,但是通过精确分子设计、组装基元分子间的相互作用调控可以更好地实现结构的精准调控;并有利于进一步通过引入功能性分子作为组装基元,实现自组装体的功能化.本文将针对肽自组装体的结构调控以及功能化两个方面对相关研究进行综述.     

自组装型紫杉醇键合物前药的合成与性能

以p-氨基苯乙酸(APA)和六亚甲基二异氰酸酯(HDI)为连接基团,将短链聚乙二醇单甲醚(mPEG)键合到紫杉醇(PTX)上,获得双亲型PTX前药mPEG-APA-PTX和mPEG-HDI-PTX.考察了这两种前药在自主装、体外药物释放动力学、体外细胞毒性和体内血浆清除速率等方面的表现.结果表明:两前药均能在水中自组装形成稳定的纳米颗粒,载药量高达28％;mPEG-HDI-PTX纳米颗粒在水溶液中非常稳定,细胞毒性很弱,在血液系统中清除很快,而mPEG-APA-PTX纳米颗粒在pH=7.4的环境下可缓慢释放出原药PTX,细胞毒性与临床用紫杉醇针剂Tax-ol(R)相当,体内循环时间较Taxol(R)明显延长;mPEG-APA-PTX是一种可自组装、载药量高、体内循环时间长的新型纳米前药.     

A carbanion induced synthesis of highly congested pyrazole and imidazole containing heterocycles

An efficient approach to the synthesis of highly congested di, penta and hexacyclic pyrazoles as well as imidazole fragment containing novel heterocyclic molecule has been developed through a carbanion induced transformation of suitably functionalized 2H-pyran-2-ones, benzo[h]chromene and thiochromeno[4,3-b]pyrans. Due to the presence of fluorescence, we report their prime application metal sensor as off/on switching in ferric ions.     

α-Amino acid derived enaminones and their application in the synthesis of N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates and other heterocycles

A new and simple synthesis of novel N-protected methyl 5-substituted-4-hydroxypyrrole-3-carboxylates, which exist in equilibrium with their 4-oxo tautomers, has been developed in two steps starting from N-protected α-amino acids. The key intermediates are enaminones, which can also be isolated, characterized, and used for the construction of other functionalized heterocycles, before they spontaneously decompose to pyrrole products. 4-Hydroxypyrroles are prone to partial aerial oxidation but can be efficiently alkylated or reduced to stable polysubstituted pyrrolidine derivatives.     

Specific intramolecular aromatic CH insertion of diazosulfonamides

The chemoselectivity in the intramolecular CH insertion of various diazosulfonamides has been experimentally studied. The results reveal that the aliphatic 1,4-, 1,5-, or 1,6-C(sp³)?H insertions of diazosulfonamides are not accessible, while the aromatic 1,5-C(sp²)?H insertion can be realized specifically by adjusting the diazo-adjacent group. In addition, the general chemoselectivities in the intramolecular CH insertions of diazosulfonyl compounds are summarized. Generally, diazosulfones undergo both aromatic 1,5-C(sp²)?H and aliphatic 1,5- and 1,6-C(sp³)?H insertions, while diazosulfonates undergo aliphatic 1,5- and 1,6-C(sp³)?H insertions. However, diazosulfonamides only undergo aromatic 1,5-C(sp²)?H insertion.     

N-Heterocyclic carbene-palladacyclic complexes: synthesis,characterization and their applications in the C-N coupling and α-arylation of ketones using aryl chlorides

N-Heterocyclic carbene-palladacyclic complexes 3 were successfully achieved in a one-pot procedure under mild conditions. The structure of 3a was unambiguously confirmed by X-ray single crystal diffraction and it was an active catalyst in the Buchwald-Hartwig amination and α-arylation of ketones even at very low catalyst loadings (0.01?mol%).     

Selective synthesis of 4,5-dihydroimidazo- and imidazo[1,5-a]quinoxalines via modified Pictet–Spengler reaction

An efficient tandem approach for the selective synthesis of 4,5-dihydroimidazo[1,5-a]quinoxalines 6a–g and imidazo[1,5-a]quinoxalines 7a–h by the reaction of 2-imidazolyl anilines 4a–c with aryl aldehydes 5a–k under mild reaction conditions is described. Introduction of electron releasing alkyl groups in substrates 4a–b was found to be instrumental for the success of the reaction.     

Understanding the Diels-Alder reactivity of 1,2-azaborine analogues

The Diels-Alder reactivity of 1,2-heteroborines (H₄C₄B(H)X, X?=?NH, PH, AsH; O, S, Se) has been computationally explored by means of Density Functional Theory (DFT) calculations. The influence of the HB?=?X fragment on the reactivity of the system has been quantitatively analyzed in detail by means of the so-called Activation Strain Model (ASM) of reactivity. It is found that the interaction between these species and the dienophile is significantly stronger than that computed for their all-carbon isoelectronic counterpart, benzene. In addition, the strain energy plays a key role in the observed reactivity trends. The role of the aromaticity strength of these heteroarenes on the reactivity is also assessed.     

Synthesis of N-substituted carbazolones from α-iodo enaminones via Pd(0)-catalyzed intramolecular coupling under microwave irradiation

A variety of N-aryl and N-alkyl carbazolones were conveniently achieved in good to high yields via Pd₂(dba)₃-mediated intramolecular coupling of N-substituted α-iodo enaminones under microwave irradiation. The Pd(0)-catalyzed cyclization was found to proceed favorably with the more electron-deficient phenyl ring during the reactions involving unsymmetrical N,N-diaryl α-iodo enaminones. This unique property enables the construction of carbazolone skeleton containing nitro substituted benzenoid ring.     

Iodine-mediated oxidative Pictet-Spengler reaction using terminal alkyne as the 2-oxoaldehyde surrogate for the synthesis of 1-aroyl-β-carbolines and fused-nitrogen heterocycles

An efficient iodine-mediated oxidative Pictet-Spengler reaction in dimethyl sulphoxide (DMSO) using terminal alkynes as the 2-oxoaldehyde surrogate for the synthesis of aryl (9H-pyrido[3,4-b]indol-1-yl)methanones is described. The scope of the protocol includes the total synthesis of Fascaplysin, Eudistomins Y₁ and Y₂. The methodology is extended for preparing pyrrolo[1,2-a]-quinoxaline and indolo[1,5-a]quinoxaline derivatives. The utility of 1-aroyl-β-carbolines was demonstrated by performing palladium-catalyzed β-carboline directed ortho-C(sp2)-H functionalization of the phenyl ring with thiomethyl (SMe) group using DMSO as source and for accessing 4-aryl-canthin-6-ones.     

Facile synthesis of bicyclic 1-arylpyrazol-5-ones

In this Letter, we described a facile method for constructing fused bicyclic 1-arylpyrazol-5-one ring system. We employed various methylene-containing carboxylic acids as the substrates and proved that the pyrazolone ring closure requires activated methylene group in intermediate II. Accordingly, a series of structurally diversified, fused bicyclic 1-arylpyrazol-5-ones was prepared in moderate to high yields using the requisite substrates.     

Synthesis of substituted 2,4,5,6-tetrahydrocyclopenta[c]pyrazoles and 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles by intramolecular nitrilimine cycloaddition

Both substituted 2,4,5,6-tetrahydrocyclopenta[c]pyrazoles and 2,4,5,6-tetrahydropyrrolo[3,4-c]pyrazoles have been synthesized by the 3+2 intramolecular dipolar cycloaddition of nitrilimines to alkynes. This cyclization has been extended to more versatile 3-bromo derivatives by the use of alkynylbromides as dipolarophiles.