环氧乙烷-环氧丙烷无规共聚醚链结构的核磁共振研究

本文用NMR波谱方法研究了无规共聚醚(EPO)的链结构。首先对EPO的~1H和~(13)CNMR谱进行了讨论。并从序列结构随环氧丙烷(PO)含量的改变,分析了EPO的二元组序列和三元组序列结构,从~(13)C实验谱中归纳出EPO的取代基参数(SCS),清楚地揭示了EPO的~(13)C谱,SCS参数和序列结构之间的关系,在此基础上计算了EPO系列共聚物的序列分布和数均序列长度。     

序列可控高分子的合成及应用

序列可控高分子是指高分子链中不同单体单元按特定顺序排列的高分子.自然界中的生物大分子,如核酸分子和多肽,其精确的序列结构决定了其复杂功能的表达.受此启发,序列可控高分子的合成及序列结构与性能关系研究近年来受到了越来越多的关注.本文介绍了近年来在序列可控高分子合成方面的重要研究成果,突出介绍了本课题组在序列可控高分子方向的研究进展.最后,对序列可控高分子的应用进行了总结和展望.     

不同结构的DNA激活序列对Cas12a反式切割活性的影响

CRISPR－Cas12a系统的反式切割活性在其识别特定的DNA激活序列后被激活,这不仅能实现特定DNA靶标的直接定量分析,同时也为构建针对多种生物标志物的体外传感体系带来了新的思路。然而,已有文献中所采用的双链DNA（dsDNA）和单链DNA（ssDNA）激活序列结构多种多样,缺乏全面、系统的设计指导原则。针对该问题,该文系统研究了不同结构的DNA激活序列对LbaCas12a反式切割活性的影响。通过对比研究,得出以下结论：（1）前间区序列邻近基序（PAM）位点有助于LbaCas12a更高效地靶向结合dsDNA激活序列和ssDNA激活序列;（2）PAM近端区域缺少序列片段会降低Cas12a-crRNA定位激活序列的效率;（3）删除PAM远端序列片段有利于增强LbaCas12a的反式切割活性;（4）由于省略了dsDNA解链过程,ssDNA激活序列在激活LbaCas12a的反式切割活性方面普遍比dsDNA激活序列产生的效果更好。根据这些发现,该文提出了一种LbaCas12a所青睐的高效激活序列结构,其激活的LbaCas2a反式酶切活性较采用含PAM位点的标准dsDNA激活序列高出3.7倍。研究结果为构建基于CRISPR-Cas12a的高效体外生物传感系统提供了重要支撑。     

胆固醇修饰的非天然HR序列肽类HIV-1融合抑制剂的合成及活性初筛

将胆固醇分子通过1个半胱氨酸侧链硫醚键和1个β-丙氨酸连接臂引入到所设计的非天然HR序列抗HIV融合活性多肽的C端和N端,合成了与天然C肽序列同源性很低的非天然序列的类肽抗HIV融合分子,以考察胆固醇修饰对非天然HR序列活性的影响,探讨克服耐药性的新思路.生物活性评价结果表明,胆固醇与HR肽C端结合物抑制HIV融合活性显著提高,而连接到N端的序列则完全失去了抗病毒活性,表明所设计的非天然序列确实具有与天然序列类似的作用机制.     

人类Y染色体回文序列中的重复序列与碱基关联

利用信息论和统计学的方法并结合生物学的特征研究人类Y染色体回文序列的互信息、“n字”熵、条件熵,定量分析了回文序列的长程关联和短程关联,发现其中既存在长程关联也存在短程关联,并且它们主要是由序列中的重复序列引起的．研究表明重复序列含量越高碱基之间的关联越强．     

~(13)C-NMR研究聚丁二烯的序列结构

本文采用~13C-NMR方法研究了不同催化体系制备的聚丁二烯。经分析指出,聚丁二烯分子链的三种序列(顺-1,4-序列、反-1,4-序列和1,2-序列)和十七类脂碳碳核为~13C-NNR谱贡献了十六个谱峰。经数据的解析,得到一组计算聚丁二烯脂碳部分各谱峰化学位移的经验参数。在本文条件下,应用该组参数得到的计算值与实验值符合较好。本文确认了聚丁二烯反-1,4-序列第四峰(T_4)的存在。初步研究了聚丁二烯~13℃-NMR谱图的定量处理问题。     

二维紧密蛋白质链折叠序列的特性研究

采用完全计数法,研究了二维紧密蛋白质链在不同HP序列时的构象性质,特别是具有唯一基态能量的折叠序列的性质.对于具有N个单体的紧密蛋白质链,发现有一定比例的序列为折叠序列.在这些折叠序列中,疏水基团(H)的数目比亲水基团(P)多20%,并同200种真实蛋白质分子的疏水基团和亲水基团的结果进行了比较.对于不同的折叠序列,根据序列中其疏水基团的数目,把具有相同疏水基团数目的序列归在同一类,发现这样的序列在总的序列中的相对含量满足高斯分布.同时还对序列中H(或者P)团族大小及其分别进行了研究,发现折叠序列与无规随机序列不同.还研究了不同折叠序列在不同链长时的比热情况,发现其相转变温度TC主要与链长有关,与折叠序列无关.     

高效液相色谱/质谱法识别不同明胶酶解产物中特征多肽

在不同动物胶原蛋白序列比对基础上,利用高效液相色谱/质谱联用技术(HPLC/MS)建立一种通过特征多肽进行明胶鉴别的方法。实验以牛明胶和猪明胶为对象,序列比对结果表明,牛和猪的Ⅰ型胶原蛋白α1链和α2链均存在氨基酸序列差异。利用胰蛋白酶将牛明胶和猪明胶降解,通过HPLC/MS分析了两种明胶酶解产物中的多肽片段。结果表明:牛明胶和猪明胶酶解产物中均可检测出存在序列差异的特征性多肽,其氨基酸序列差异与两种胶原蛋白序列比对结果中的序列差异一致;酶解产物中特征多肽上的脯氨酸存在不同程度的羟基化修饰,特征多肽的相对含量主要受明胶分子量范围影响。利用HPLC/MS检测明胶酶解产物中的特征多肽是一种鉴别牛明胶和猪明胶的有效方法。     

EVAc共聚物的序列结构和它的~(13)C NMR谱的关系

本文以EVAc共聚物为例,阐述了EV共聚物序列结构的符号表示与Bovey关系(Ⅰ)的一致性。在此基础上,选择了EV共聚物序列结构的Sung表示并赋予它以化学位移的意义,在二元组和三元组序列水平上分析了EV共聚物的13种序列结构与Sung表示,与取代基参数,与其~(13)C NMR谱13个谱峰之间的一一对应关系。其主要内容由Sung表示与取代基参数之间的α～S_1,β～S_2,γ～S_3,δ～S_4,δ~+～0ppm对应关系表征,从而构架了由EV共聚物的~(13)C NMR谱通向其序列结构的桥梁,建立起研究EV共聚物序列结构的普适方法。     

基于一维序列的三维染色质相分离：驱动力、过程与功能

染色质高级结构在基因调控中起到不可忽视的作用,染色质结构的形成与调控机制受到广泛关注。"相分离"理论近年来受到较多关注,异染色质与转录因子在其中的作用引人瞩目。但是,目前的相分离模型更关注结合因子与表观遗传性质,对DNA序列自身的作用理解尚较不充分。许多物种基因组的序列分布均具有多尺度的不均一性,仅基于Cp G岛(Cp G island,CGI)密度差异这一序列性质,就可以划分出基因、表观遗传、结构和转录性质都截然不同的高CGI密度"森林"和低CGI密度"草原"两种序列区域,体现了基因组自身的马赛克性。本文聚焦染色质结构的序列依赖性,讨论了染色质结构模型的研究进展,关注在序列几乎相同的不同细胞类型中的序列–结构关系及其功能调控,对发育、分化、衰老、疾病等多种过程的染色质结构变化进行了系统分析。针对基于序列的染色质相分离模型,对其物理驱动力进行了讨论,并在该模型的框架下基于相分离的物理特性,对温度、序列不均一性等物理因素对染色质结构可能造成的影响进行了探讨。     

MICROSTRUCTURES AND SEQUENCE DISTRIBUTIONS IN POLYDIENES

The sequence distribution of polydienes is studied both theoretically and experimentally. The expressions for sequence length distribution, the probability functions for monads and dyads are derived from solving a set of kinetic differential equations on the condition of constant monomer concentration [M]. The microstructure data of polybutadiene generated by anion and Ziegler-Natta catalyst at low conversion or in the case of constant [M] show that our theory mentioned above is correct, i. e. as in the case of batch reactor, there is also an unsteady stage during the initial period of polymerization for the system of constant [M] when the sequence structures of the product vary with reaction time; then the polymerization arrives at the steady stage when the microstructures become unchanging.     

Carbon-13 nuclear magnetic resonance quantitative measurements of monomer sequence distributions in hydrogenated polybutadienes

The 1,4–1,2 additions in three hydrogenated polybutadienes are described in terms of triads of monomer units, average sequence lengths, and branches per 1000 carbon atoms. A test for conformity with Markov statistical behavior shows that the measured triad distributions can be closely reproduced assuming a first-order model. Transition probabilities from the statistical analysis can be used to calculate the relative concentration of any desired sequence. Steric factors during polymerization may lead to the first-order bias in the monomer distribution.     

Kinetics theory of anionic copolymerization with constant monomer ratio, 1. Sequence distribution

The chain microstructure of copolymers generated via anionic copolymerization with constant monomer ratio is studied theoretically by using the linear operator technique to solve the kinetic differential equations. The microstructural parameters for copolymers, such as the functions of sequence distributions, average length of the sequence and fractions of dyads and triads, are derived and further connected with initial conditions and reaction time so that one can predict the chain microstructure for copolymers from the polymerization conditions.     

Theoretical study of sequence distributions in polydienes. II. Non-steady-state analysis of a bernoullian process

With the aid of the non-steady-state kinetic method, the sequence distribution of polydienes conforming to a Bernoullian process is treated theoretically. The expressions for sequence length distribution, the probability functions, and other structural parameters are derived in closed form. The results obtained show that at the beginning of polymerization all the parameters mentioned vary with reaction time, monomer conversion, and the ratio of initial concentrations of monomer to initiator, but monotropically approach their respective limits which are identical with those derived from statistics.     

Kinetics of self‐condensing vinyl hyperbranched polymerization in three‐dimensional space

Self‐condensing vinyl hyperbranched polymerization (SCVP) with A‐B* type monomer is simulated applying Monte Carlo method using 3d bond fluctuation lattice model in three‐dimensional space. The kinetics of SCVP with zero active energy of reaction is studied in detail. It is found that the maximal number–average and weight–average polymerization degrees and the maximal molecular weight distribution, at varying the initial monomer concentration and double bond conversion, are about 52, 190, and 3.93, respectively, which are much lower than theoretical values. The maximal average fraction of branching points is about 0.27, obtained at full conversion at the initial monomer concentration of 0.75. The simulation demonstrated the importance of steric effects and intramolecular cyclization in self‐condensing vinyl hyperbranched polymerization. The results are also compared with experiments qualitatively and a good agreement is achieved. © 2008 Wiley Periodicals, Inc. J Polym Sci Part A: Polym Chem 46: 4486–4494, 2008     

Kinetic theory of anionic copolymerization with constant monomer ratio, 2 . Molecular weight distribution

The kinetic differential equations for the anionic copolymerization with constant monomer ratio are treated by Laplace transformation and a graphical technique. A theoretical method is established by which all molecular parameters of the copolymers, such as the molecular distribution (MWD), the average molecular weight and the polydispersity, can be calculated from reaction rate constants, initial conditions and polymerization time. Three-dimensional plots obtained by numerical computation are presented to illustrate the influence of the reaction conditions on the MWD's of the copolymers.     

Synthesis of monodisperse polystyrene microspheres by dispersion polymerization using sodium polyaspartate

We prepared monodisperse polystyrene microspheres by dispersion polymerization using sodium polyaspartate (PAspNa) as a dispersion stabilizer in an ethanol/water medium. The influence of reaction parameters, i.e., the volume fraction of ethanol in the medium, stabilizer concentration, and the monomer concentration, on the average diameter of the prepared polystyrene microspheres and its distribution were investigated. Polystyrene microspheres were successfully prepared, and the average diameter of the prepared monodisperse polystyrene microspheres was controlled by adjusting the reaction parameters. The zeta potential of the microspheres and the time course of conversion, the particle diameter and its distribution, and particle numbers were also examined. It was found that PAspNa as a dispersion stabilizer provides an environmentally benign process for the preparation of monodisperse polymer microspheres by dispersion polymerization.     

Translocation of a heterogeneous polymer

We present results on the sequence dependence of translocation kinetics for a partially charged heteropolymer moving through a very thin pore using theoretical tools and Langevin dynamics simulational techniques. The chain is composed of two types of monomers of differing frictional interaction with the pore and charge. We present exact analytical expressions for passage probability, mean first passage time, and mean successful passage times for both reflecting/absorbing and absorbing/absorbing boundary conditions, showing rich and unexpected dependence of translocation behavior on charge fraction, distribution along the chain, and electric field configuration. We find excellent qualitative and good quantitative agreement between theoretical and simulation results. Surprisingly, there emerges a threshold charge fraction of a diblock copolymer beyond which the success rate of translocation is independent of charge fraction. Also, the mean successful translocation time of a diblock copolymer displays non-monotonic behavior with increasing length of the charged block; there is an optimum length of the charged block where the mean translocation rate is the slowest; and there can be a substantial range of higher charge fractions which make the translocation slower than even a minimally charged chain. Additionally, we find for a fixed total charge on the chain, finer distribution along the backbone significantly decreases mean translocation time.     

Inclusion of the effects of polydispersity and volatility on the random chain scission statistical analysis for polymer degradation

The statistical product distribution for a linear polydisperse polymer of finite molecular weight was included into the statistical analysis for a system undergoing random chain scission showing the effect of volatilization of species other than monomer. Two sets of equations were derived. One set is for the nonvolatile fraction; the other is for the volatile fraction. Within each set there are three equations, one for the number of polymer molecules, the second for the molar (or number) fraction, and the third for the weight fraction of polymer molecules containing a specific number of repeat units. As degradation proceeds the polydispersity index should converge to a value of 1 rather than 2, which has been reported previously. The expected effects of polydispersity, number‐average degree of polymerization, and volatility were treated individually, and we determined that the molecular weight of a polymer has no theoretical influence on the product distribution. As for the effect of volatility, we determined that only the volatile product distribution would change. © 2000 John Wiley & Sons, Inc. J Polym Sci A: Polym Chem 38: 3690–3696, 2000     

Nonlinear depression of the lower critical solution temperatures in aqueous solutions of thermo-sensitive random copolymers

We develop a theoretical model of cooperative hydration to clarify the molecular origin of the observed nonlinear depression of the lower critical solution temperature (LCST) in the aqueous solutions of thermosensitive random copolymers and find the monomer composition at which LCST shows a minimum. Phase diagrams of poly(N-isopropylacrylamide-co-N,N-diethylacrylamide) copolymer solutions are theoretically derived on the basis of the theory of cooperative hydration by introducing the microscopic structure parameter η which characterizes the distribution of the monomer sequences along the chains. We compared them with the experimental data of LCST of random copolymers with various monomer compositions and also of the diblock copolymers with equimolar monomer composition. The transition temperature shifts to lower than those of homopolymer counterparts when the monomer sequence of the chains has an alternative tendency. On the contrary, for the blocky polymers such as diblock copolymers, the transition temperature remains almost the same as those of the homopolymers. Thus, the nonlinear effect in phase separation appears when the average block length of the copolymers is shorter than the average sequence length of the cooperative hydration. The degree of hydration is calculated as a function of the temperature and polymer concentration for varied distribution of the copolymer compositions. © 2013 Wiley Periodicals, Inc. J. Polym. Sci., Part B: Polym. Phys. 2013, 51, 1112–1123