Synthesis of Peptoid Nucleic Acid with Thymine as Nucleic Base

The synthesis of peptoid nucleic acid bearing thymine as nucleobase has been achieved. This modified oligonucleotide showed good hybridization with DNA.

Peptoids with aliphatic sidechains as helical structures without hydrogen bonds and collagen/ inverse-collagen type structures

Aliphatic homo-polypeptoids of NAla, NVal, NIle and NLeu both in the presence and absence of protecting groups adopt helical structures without hydrogen bonds with Φ, Ψ values of ~ 0, ± 90° with trans amide bonds. These structures are stabilized by carbonyl-carbonyl interactions and characterized by ~ 3.16 residues per turn with a pitch of ~ 6.13 ?. It has been shown that like polyvaline and polyleucine peptides, poly-peptoids can also be exploited for the construction of potential surfactant like molecules by incorporating charged amino acid residues at the N terminal. A single-handed template with Φ, Ψ values of ~ 0, 90° can be attained by incorporating L-leu or L-val at the C-terminal of poly-NIle. Analysis of the simulation results in water as a function of time reveals that the opening of helical structures without hydrogen bonds takes place at sub-picosecond time scale starting from the N-terminal. This leads to the formation of collagen or inverse-collagen type structures (Φ, Ψ ~ -60, 145° and 60, -145° respectively) stabilized by interactions of water molecules with the backbone carbonyl groups.

Assembly of highly efficient aqueous light-harvesting system from sequence-defined peptoids for cytosolic microRNA detection

Precisely controlled spatial distributions of artificial light-harvesting systems in aqueous media are of significant importance for mimicking natural light-harvesting systems;however,they are often restrained by the solubility and the aggregation-caused quenching effect of the hydrophobic chromophores.Herein,we report one highly efficient artificial light-harvesting system based on peptoid nanotubes that mimic the hierarchical cylindrical structure of natural systems.The high crystallinity of these nanotubes enabled the organization of arrays of donor chromophores with precisely controlled spatial distributions,favoring an efficient Förster resonance energy transfer(FRET)process in aqueous media.This FRET system exhibits an extremely high efficiency of 98.6%with a fluorescence quantum yield of 40%and an antenna effect of 29.9.We further demonstrated the use of this artificial light-harvesting system for quantifying miR-210 within cancer cells.The fluorescence intensity ratio of donor to acceptor is linearly related to the concentration of intercellular miR-210 in the range of 3.3–156 copies/cell.Such high sensitivity in intracellular detection of miR-210 using this artificial light-harvesting system offers a great opportunity and pathways for biological imaging and detection,and for the further creation of microRNA(miRNA)toolbox for quantitative epigenetics and personalized medicine.

Azobenzene-based ultrathin peptoid nanoribbons for the potential on highly efficient artificial light-harvesting

The development of artificial light-harvesting systems based on long-range ordered ultrathin organic nanomaterials(i.e., below3 nm), which were assembled from stimuli-responsive sequence-controlled biomimetic polymers, remains challenging. Herein,we report the self-assembly of azobenzene-containing amphiphilic ternary alternating peptoids to construct photo-responsive ultrathin peptoids nanoribbons(UTPNRs) with a thickness of ~2.3 nm and the length in several micrometers. The pendants hydrophobic conjugate stacking mechanism explained the formation of one-dimensional ultrathin nanostructures, whose thickness was highly dependent on the length of side groups. The photo-isomerization of azobenzene moiety endowed the aggregates with a reversible morphology transformation from UTPNRs to spherical micelles(46.5 nm), upon the alternative irradiation with ultraviolet and visible light. Donor of 4-(2-hydroxyethylamino)-7-nitro-2,1,3-benzoxadiazole(NBD) and acceptor of rhodamine B(RB) were introduced onto the hydrophobic and hydrophilic regions, respectively, to generate photocontrollable artificial light-harvesting systems. Compared with the spheres-based systems, the obtained NBD-UTPNRs@RB composite proved a higher energy transfer efficiency(90.6%) and a lower requirement of RB acceptors in water. A proof-ofconcept use as fluorescent writable ink demonstrated the potential of UTPNRs on information encryption.

Investigation of Peptoid Chiral Stationary Phases Terminated with N＇-Substituted PhenyI-L-proline/leucine Amide

Eight peptoid chiral stationary phases （CSPs） terminated with N＇substituted phenyl-L-proline or L-leucine amide were prepared and evaluated under normal phase mode. With 59 racemic analytes, we compared the enantio- meric separations on CSPs terminated with p-methylphenyl, p-chlorophenyl and unsubstituted phenyl. For short peptoid selectors containing only one S-N-（1-phenylethyl） glycine （Nspe） unit, the terminal p-methyl substituent did not affect chiral recognition abilities significantly. In L-proline amide terminated CSPs, p-chloro substituent resulted in obviously inferior selectivity while in L-leucine amide terminated CSPs, it worked much better. Longer peptoid selectors containing two more Nspe units generally performed much better than the shorter ones, due to the great contributions of peptoid chain to chiral recognition. Meanwhile, the effects of the terminal substituent on selectivity were found changed on these CSPs. For CSPs terminated with L-leucine amide, the terminal p-chloro substituent in longer selector no longer produced the best recognition ability; the CSP with unsubstituted phenyl instead performed best. Comparison of these peptoid CSPs varied in terminal substituents and chain length was conducted to gain a better understanding of the chiral recognition mechanism of this type CSP and promote the development of more useful CSPs.

Blockade of CD28 by a synthetical peptoid inhibits T-ce proliferation and attenuates graft-versus-host disease

CD28 is one of the costimulatory molecules crucial for T-cell activation and thus has become an attractive target for therapeutic immunomodulation. Conventional strategies for blocking CD28 activity using monoclonal antibodies, Fab fragments, antagonistic peptide and fusion proteins, have apparent disadvantages such as inherent immunogenicity, unwanted Fc signaling, poor tissue penetration and bioinstability. Recent research has been directed toward the creation of non-natural, sequence-specific biomimetic oligomers with bioinspired structures that capture the amino-acid interface of the targeted proteins. One such family of molecules is the poly-N-substituted glycines or peptoids, which have close structural similarity to peptides but are essentially invulnerable to protease degradation. To screen for peptoids that specifically target CD28, we first designed and chemically synthesized 19 candidate peptoids based on molecular modeling and docking. Using the phage-displaying system that expresses the extracellular domain of the CD28 homodimer and contains the core B7-binding motif, a peptoid （No. 9） with a molecular formula of C21H29N307, was identified to display the highest binding activity to CD28. This peptoid not only inhibited the lymphocyte proliferation in vitro, but suppressed immunoresponses against alloantigens in vivo, and attenuated the graft-versus-host disease in a mouse bone-marrow transplantation model. These results suggested that peptoids targeting CD28 are effective agents for blocking the CD28-mediated costimulation and suitable for development of novel therapeutic approaches for diseases involving this pathway.

Synthesis and biological evaluation of tetrahydroisoquinoline derivatives as potential multidrug resistance reversal agents in cancer

Tetrahydroisoquinoline derivatives were synthesized and their multidrug resistance reversal activities were evaluated in vitro. The results showed that some of the synthetic compounds had higher multidrug resistance （MDR） reversal activities than verapamil.

利用多中心合成方法同步合成含N-取代甘氨酸的类肽化合物(英文)

N-取代甘氨酸聚合体是一类新的聚合体化合物,同多肽相比,N-取代甘氨酸聚合体具有抗酶解稳定性,同时使用市售的伯胺作为构建单元(building block)大大地扩展了天然多肽分子结构的多样性,本文报道了利用多中心多肽合成方法合成了九个含N-取代甘氨酸聚合体多肽杂合休,由于此类聚合体具有抗酶的能力,因此可用于蛋白酶抑制剂的研究。

含NSG残基取代的RGD相关肽的固相合成

目的:应用固相肽合成方法制备RGD肽类似物。方法:用NSG残基Ida代替Asp,用酰甲胺或酰乙胺代替C末端的羧基,生成N取代类肽型的产物。结果:五个RGD肽类似物结构经LC-MS分析证明,总收率均在85%以上。结论:通过本合成工作,为建立经济、可行的类肽合成提供了一种途径。

精氨酸-甘氨酸-天冬氨酸肽类似物的固相合成(英文)

【目的】含有Arg-Gly-Asp(精氨酰甘氨酰天冬氨酸,RGD)片段的多肽可以识别整合素受体家族,但是这些含RGD小肽在体内很容易被蛋白酶降解。本研究设计并合成RGD肽类似物,通过结构改造克服这一缺点,以期开发新的高效的抗肿瘤药物。【方法】分子设计采用N取代甘氨酸(NSG)残基替代法,即用NSG残基Ida代替Asp、用酰甲胺或酰乙胺代替C末端的羧基,生成N取代类肽型的产物;化学合成采用Boc保护策略,在Merrifield树脂上逐步固相合成N取代类肽型的产物。【结果】全部RGD肽类似物结构均经LC-MS分析证明,总收率在85%以上,纯度>95.1%。【结论】通过本合成工作,为建立经济、可行的类肽合成提供了一种有效途径。

植物水孔蛋白PIP2表达量快速无标记检测

相较于传统的抗体检测,适配体更易于大量快速合成,且可和多种检测技术相结合,在蛋白检测方面具有巨大的潜力.水孔蛋白作为生物体内水分跨膜运输的主要途径,了解其表达量的变化在植物水代谢研究中有着重要意义.利用传统的混合列分法构建了8个C端恒定半胱氨酸残基的类肽适配体文库,结合表面等离激元共振成像技术,筛选得到能特异性结合高等植物水孔蛋白PIP2的类肽适配体PPA7,其亲和力 K D高达2.52×10 -9 mol/L.利用PPA7检测了石竹玻璃化和正常植株的水孔蛋白表达量,结果表明,石竹玻璃化植株的水孔蛋白表达量显著高于正常植株.研究提供了一种新的植物蛋白定量检测策略,也为进一步明确水孔蛋白在组培苗玻璃化发生中的作用奠定了基础.

N,N′-双取代-L-谷氨酰胺类肽化合物的合成与抑瘤活性研究

设计合成了 7个谷氨酰胺小分子类肽化合物。对肺腺癌细胞体外初步抑瘤活性实验表明 ,化合物 1b、1g在16 0 μg/m l的剂量下 ,抑制率高于对照品抗瘤酮

超分子类肽纳米片层的全自动高通量制备

类肽是以N-取代甘氨酸为合成单元的类似多肽的非天然化合物。类肽保留了多肽可折叠可自组装的优点,同时类肽组成单元的多样性导致其结构多样性,使得类肽获得比多肽更多样的化学、生物活性。目前,其良好的生物活性和药理性质使得人们开始关注其在化学、生物和药学等领域应用。我们开发一种非朗缪尔槽的方法,利用少量样品就可以高效进行全自动和高通量的两维类肽纳米片层的制备,该方法可快速优化类肽自组装的条件,并可以用在其它肽类超分子的自组装研究。

两类类肽图的Wiener指标

文献[1]中给出了线性骨架类肽图的Wiener指标,文章结合实际给出了两类骨架更为复杂的类肽图的Wiener指标的计算方法,即当骨架图分别为完全图和轮时的类肽图的Wiener指标的计算方法及其精确结果。

类肽图的Wiener指标

结合实际利用图论方法给出了一类骨架更复杂的类肽图当骨架图为轮时的类肽图的Wiener指标的计算方法及其精确结果.同时还得到了一般类肽图的Wiener指标的计算方法.本研究结果为与Wiener指标有关的研究提供数据库.

Biomimetic ultrathin pepsomes for photo-controllable catalysis

Artificial vesicles for mimicking the unique structures and functions of natural organelles represent a promising scientific object in biomimicry.However,the development of the stimuli-responsive and ultrathin vesicles assembled from sequence-defined biomimetic polymers for controllable applications is still a significant challenge.Herein,we report the self-assembly of azobenzene-based amphiphilic alternating peptoids to generate photo-responsive and ultrathin peptoid vesicle(pepsomes)with an average diameter of∼180 nm.Both cryo-transmission electron microscopy(TEM)and dissipative particle dynamics simulation proved that the vesicular membrane was the ultrathin bilayer structure around∼1.6 nm.The photo-responsive ability of pepsomes was demonstrated by the reversible size changes upon the alternative irradiation with ultraviolet(UV)and visible lights,which was attributable to the photoisomerization virtue of azobenzene moiety.As a proof-of-concept,the photo-controllable catalytic action of gold nanoparticles-decorated pepsomes was evaluated toward the borohydride-mediated reduction from 4-nitrophenol to 4-aminophenol.Photo-controllable reversible and recyclable catalytic activity was effectively modulated using the alternative irradiation with UV and visible lights for five cycles.Our work provides a simple strategy to prepare stimuli-responsive and ultrathin vesicles for potential application on nanocatalysis.

Telechelic Triblock Poly(α-Amino Acid)-Poly(Tetrahydrofuran)-Poly(α-Amino Acid)Copolymers:Chain-End Transformation,Polymerization and pH-Responsive Hydrolysis

Main observation and conclusion Block copolymers not only combine properties of different segments but also generate new application prospects.Poly(α-amino acid)-b-poly(tetrahydrofuran)-b-poly(α-amino acid)(PAA-PTHF-PAA)is one of the copolymers.In this contribution,di-hydroxyl-ended HO-PTHF-OH is transferred into di-oxyamino-ended H2NO-PTHF-ONH2 quantitatively,which is used as a macroinitiator to polymerize sarcosine N-thiocarboxyanhydride(Sar-NTA)and N-phenyoxycarbonyl N-ε-carbobenzyloxy-D-lysine(ZDL-NPC).Well-defined triblock PAA-NHO-PTHF-ONH-PAA is produced with high molecular weight(up to 25.3 kg/mol)and narrow dispersity.The amphiphilic PSar-NHO-PTHF-ONH-PSar(STS)self-assembles into micelles with uniform diameters of 30—40 nm according to DLS.Owing to oxygen amide groups inside the backbone of these copolymers,the polyether-poly(amino acid)s block copolymers are cleavable under an acidic environment and therefore have potential applications in smart biomedicine and engineering.

聚酰胺类多肽二级结构模拟物的结构设计与性质分析

多肽与蛋白质具有结构支持、酶促催化、蛋白-蛋白相互作用等一系列功能。其中,二级结构作为少数氨基酸参与的相对局域性的结构,是一切高级结构的基础。为了模拟天然多肽的结构与功能,人们成功设计并合成了多种非天然的寡聚物结构。这些拟肽或类肽结构能有效地模拟以α-螺旋、转角为主体的多肽二级结构。二级结构模拟物具有重要的理论意义,并被进一步用于蛋白-蛋白相互作用的抑制剂研究与新药设计中。本文从分析多肽的二级结构特征入手,分类阐述了目前的各类多肽二级结构模拟物,并重点分析了最为主要的基于酰胺键型的模拟物的设计与结构多样性。同时,本文提出一系列形象化的命名手段进行分类,如χ肽、ζ/ξ-肽及ζ-ξ-肽等。

基于类肽等级自组装结构仿生纳米材料:合成,表征和应用

类肽(或N-取代甘氨酸)具有合成效率高、化学稳定性强、抗酶水解及生物相容性好等优点,是一类潜在的可自定义序列的生物仿生聚合物.通过调节类肽的侧链化学,可以精确地控制类肽序列并实现侧链的多样性.基于以上类肽分子独特的优势,在过去的几年里,研究者设计和合成了大量的双亲性类肽作为基本的结构单元,通过自下而上的分子自组装作用构建了结构可控和具有特定功能的仿生纳米材料.本文从以下三个方面综述了我们在类肽自组装领域取得的一些成果.首先,概述了以云母和硅片为无机基底辅助类肽自组装.将原子力显微镜原位成像技术和单分子力谱技术相结合,可实时观察类肽分子在表面的组装过程并直接测定类肽分子与基底间的相互作用,揭示基底表面对类肽自组装的影响.其次,介绍了类肽分子在溶液中自组装成纳米管和具有自修复功能的纳米薄膜.最后,综述了基于类肽自组装纳米材料的应用,包括以类肽自组装纳米材料为催化模板构建纳米仿生催化剂和作为细胞内输送物质的载体等.