多肽片段连接方法及肽硫酯和肽醛的合成*

本文综述了多肽和蛋白质合成中的片段连接方法,这是近年来多肽和蛋白质合成领域中方法学上的重要进展.该方法使用非保护的多肽片段,无需酶或化学活化试剂,在缓冲溶液中能够高产率地获得多肽和蛋白质.还介绍了与多肽片段连接有关的肽硫酯和肽醛的合成方法.     

肽自组装水凝胶的制备及在生物医学中的应用

短肽自组装水凝胶作为一种新型的生物材料,具有生物相容性高、免疫原性低、含水量高、降解产物可被机体重吸收利用、结构与天然细胞外基质类似等优点,使其在材料科学、生物医药及临床医学等领域具有广阔的应用前景。在这篇综述中,我们主要介绍了常用的几种制备稳定的肽自组装水凝胶方法,包括酶催化的水凝胶化、化学/物理交联的水凝胶化以及光催化的水凝胶化。进一步,我们介绍一些关于肽自组装水凝胶在药物递送和抗肿瘤治疗、抗菌和伤口愈合以及3D生物打印和组织工程中的应用。我们希望通过本文的论述能引起更多的人对肽自组装水凝胶的关注,以推进其在生物医学领域应用的发展。     

Review: Examining the Natural Role of Amphibian Antimicrobial Peptide Magainin

Host defense peptides (HDPs) are a group of antimicrobial peptides (AMPs) that are crucial components of the innate immune system of many different organisms. These small peptides actively kill microbes and prevent infection. Despite the presence of AMPs in the amphibian immune system, populations of these organisms are in decline globally. Magainin is an AMP derived from the African clawed frog (Xenopus laevis) and has displayed potent antimicrobial effects against a wide variety of microbes. Included in this group of microbes are known pathogens of the African clawed frog and other amphibian species. Arguably, the most deleterious amphibious pathogen is Batrachochytrium dendrobatidis, a chytrid fungus. Investigating the mechanism of action of magainin can help understand how to effectively fight off infection. By understanding amphibian AMPs’ role in the frog, a potential conservation strategy can be developed for other species of amphibians that are susceptible to infections, such as the North American green frog (Rana clamitans). Considering that population declines of these organisms are occurring globally, this effort is crucial to protect not only these organisms but the ecosystems they inhabit as well.     

从组合化学肽库中筛选亲和配基

在亲和色谱研究中 ,建立适合于某种分离对象的亲和色谱体系的关键是寻找适合的亲和配基 .小肽亲和配基具有性质稳定、合成简单、价格低及生物相容性好等特点[1] ,但这类配基也存在着亲和力弱或选择性低的缺点 .因此 ,如何寻找小肽配基以及如何提高小肽配基的亲和力和选择性的问题引起了人们的关注与重视 [1～ 3 ] .组合化学法是一种快速制备大量相关或同类化合物的革新性的方法 [4 ] ,组合肽库包括噬菌体展示肽库和合成肽库 ,这两类肽库均可用于小肽配基的筛选与优化 [1,5] .组合化学法尽管有效 ,但以小肽为目的物进行筛选时 ,往往因肽 -肽…     

A Novel Peptide from Buthus martensii Karch

A novel peptide was purified and characterized from Buthus martensii Karch.The peptide,named BmK M6,is a single-chain polypeptide cross-linked by four intramolecular disulfide bridges.The molecular weight of the peptide was determined by MOLDI-TOF-MS as 7034 Da.The partial amino acid sequence of BmK M6 from N-terminal is VRDAYIAKPEN CVYECGITQDCNKLCTENG.     

Effects of Heat Shock on Glucocorticoid Receptor

The changes of glucocorticoid receptor (GR) during the heat shock response have been studied using a human osteosarcoma cell line (HOS-8603) as the model. The expression of the heat shock protein 70 (hsp70) mRNA in HOS-8603 cells has been enhanced markedly after a heat treatment at 43 ℃ for 30 min. A mild thermal pretreatment (42℃ for 1 h) protects the HOS-8603 cells against a subsequent heat challenge (46℃). This induced thermotolerance is reflected by the increase of cell viability of HOS-8603 cells. The GR binding activity in HOS-8603 cells decreased rapidly after the heat treatment at 43℃; only 42. 61% of controls were detected 60 min after the heat treatment. However, there was no significant change in the dissociation constant value (Kd). These results indicate that the heat shock induce not only the heat shock mRNA expression, but also the rapid reduction in GR binding activity, suggesting that there might be a functional relationship between GR action and the heat shock response.     

Supramolecular Chemistry of Peptide Bundles

Amphiphilic octadecapeptides containing 8～9 leucines in the hydrophobic phase wete syn-thesized and shown to self-associate to form α-helical hexamers. The NMR spectra of molecular com-plexes from such peptides and substrate 1 showed that these hexamers exist as a twisted helical bundlecontaining an annular space in its middle.     

合成多肽疫苗研究进展

综述了合成多肽疫苗的研究进展,系统地介绍了目前寻找抗原肽的各种方法以及各类可用作疫苗接种的合成多肽抗原的制备和应用.     

肽类自组装研究进展*

近年来,多肽自组装因其结构多样性及在生命科学领域中良好的应用前景而逐渐成为人们研究的热点。本文总结了目前国内外多肽自组装方面的研究进展,并对肽类自组装形成的多种形态结构进行了介绍,同时也就自组装机制和影响因素进行了分析和探讨。     

基因网络前馈环路中的涨落共振

应用化学主方程和线性涨落近似方法,重点研究了前馈环路（FFL）对外界输入弱信号的响应,特别考察了它的涨落共振现象．研究发现Z基因的FR行为很大程度上依赖于FFL的协同性：协同FFL中Z的FR曲线呈明显的单峰,而非协同FFL中该曲线出现明显双峰．由于振荡信号常常在实际应用中用来探测网络的调控结构,因此可以利用涨落共振曲线的定性差别来区分FFL网络的性能．     

1-Ethyl-2-Fluoro Pyridinium Salt: A Highly Efficient CouplingReagents for Sterically Hindered Peptide Synthesis

Moreand"loreattentionfortheincorporationof,\l'-methylorC'.,(;'.-dialkylaminoacidresiduesintopeptideshasbeenpaidinviewoftheincreasingnumberofisolatednaturally-occurrillgpeptidebearingstericallyhinderedanlinoacidunits.suchasMeValalldAib.However.thechainelongationofsuchpeptideisotienineftlcientusillgconventionalpeptidecouplingreagents,suchasHOBt-basedphosphonium'.uronium:andimmoniUm;typereagents.Recently,HOAt-derivedoniumsalts'and11alogeneratedoniumsalts'wereshowntobeeffectiveforthesynthesiso…     

有机磷试剂在肽合成中的应用

本文综述有机磷试剂在肽合成中的应用情况,介绍了各种用作氨基保护试剂的磷(膦)酰氯及硫代膦酰氯和四价鏻盐;并着重介绍了不同价态的有机磷试剂用于羧基活化的发展状况。 . t     

树状多肽的合成及应用

树状多肽作为树枝状大分子的一种,具有不同于链状多肽的独特理化特性,在生物学领域中具有广泛的应用.本文简要综述了树状多肽的合成方法,及其在诱导免疫反应、生物分子模拟、免疫诊断试剂、人工酶、药物及基因载体等方面的应用.     

Nano‐Bio Engineered Carbon Dot‐Peptide Functionalized Water Dispersible Hyperbranched Polyurethane for Bone Tissue Regeneration

The present study delves into a combined bio‐nano‐macromolecular approach for bone tissue engineering. This approach relies on the properties of an ideal scaffold material imbued with all the chemical premises required for fostering cellular growth and differentiation. A tannic acid based water dispersible hyperbranched polyurethane is fabricated with bio‐nanohybrids of carbon dot and four different peptides (viz. SVVYGLR, PRGDSGYRGDS, IPP, and CGGKVGKACCVPTKLSPISVLYK) to impart target specific in vivo bone healing ability. This polymeric bio‐nanocomposite is blended with 10 wt% of gelatin and examined as a non‐invasive delivery vehicle. In vitro assessment of the developed polymeric system reveals good osteoblast adhesion, proliferation, and differentiation. Aided by this panel of peptides, the polymeric bio‐nanocomposite exhibits in vivo ectopic bone formation ability. The study on in vivo mineralization and vascularization reveals the occurrence of calcification and blood vessel formation. Thus, the study demonstrates carbon dot/peptide functionalized hyperbranched polyurethane gel for bone tissue engineering application.

     

HF‐Free Boc Synthesis of Peptide Thioesters for Ligation and Cyclization

We have developed a convenient method for the direct synthesis of peptide thioesters, versatile intermediates for peptide ligation and cyclic peptide synthesis. The technology uses a modified Boc SPPS strategy that avoids the use of anhydrous HF. Boc in situ neutralization protocols are used in combination with Merrifield hydroxymethyl resin and TFA/TMSBr cleavage. Avoiding HF extends the scope of Boc SPPS to post‐translational modifications that are compatible with the milder cleavage conditions, demonstrated here with the synthesis of the phosphorylated protein CHK2. Peptide thioesters give easy, direct, access to cyclic peptides, illustrated by the synthesis of cyclorasin, a KRAS inhibitor.     

多肽和蛋白质的聚乙二醇化修饰方法

聚乙二醇是一类具有独特理化性质的大分子聚合物。多肽和蛋白质类药物经聚 乙二醇共价修饰后能明显改善其药代学和药效学性质，如降低免疫原性、增加对蛋 白水解酶的稳定性、增加水溶性及延长体内的半衰期等。蛋白质的聚乙二醇化修饰 研究已取得较好的效果，多肽的聚乙二醇化修饰研究起步较晚。对近年来多肽和蛋 白质的聚乙二醇化修饰方法进行了综述，主要介绍了对多肽和蛋白质的N端、C端及 某些氨基酸侧链进行选择性聚乙二醇化修饰的方法。     

Regulatory T-cell vaccination independent of auto-antigen

To date, efforts to treat autoimmune diseases have primarily focused on the disease symptoms rather than on the cause of the disease. In large part, this is attributed to not knowing the responsible auto-antigens (auto-Ags) for driving the self-reactivity coupled with the poor success of treating autoimmune diseases using oral tolerance methods. Nonetheless, if tolerogenic approaches or methods that stimulate regulatory T (T_reg) cells can be devised, these could subdue autoimmune diseases. To forward such efforts, our approach with colonization factor antigen I (CFA/I) fimbriae is to establish bystander immunity to ultimately drive the development of auto-Ag-specific T_reg cells. Using an attenuated Salmonella vaccine expressing CFA/I fimbriae, fimbriae-specific T_reg cells were induced without compromising the vaccine''s capacity to protect against travelers'' diarrhea or salmonellosis. By adapting the vaccine''s anti-inflammatory properties, it was found that it could also dampen experimental inflammatory diseases resembling multiple sclerosis (MS) and rheumatoid arthritis. Because of this bystander effect, disease-specific T_reg cells are eventually induced to resolve disease. Interestingly, this same vaccine could elicit the required T_reg cell subset for each disease. For MS-like disease, conventional CD25⁺ T_reg cells are stimulated, but for arthritis CD39⁺ T_reg cells are induced instead. This review article will examine the potential of treating autoimmune diseases without having previous knowledge of the auto-Ag using an innocuous antigen to stimulate T_reg cells via the production of transforming growth factor-β and interleukin-10.     

Secondary Structure in Solution of an Analog of Salmon Calcitonin:[Val~1, Ala~7]sCT

Calcitoninisacyclicpeptidewith32residues.Alth0ughtherearemanydifferencesinindividuaIaminoacidsincalcitoninsfr0mdifferentsPScies-theyallhaveadisulfidebridgebetweencysteineresiduesatp0sitionsland7;andtheC-terminusisalwaysprolineamide.Salmoncalcit0nin(sCT)iskn0wnmainlyf0ritshighesthyp0calcemiceffectam0ngcalcit0nins.AlthoughthedisulfidebridgeintheN-terminalregion0fdifferentcalcitoninsisessentialforthebiologicalactivity0fhumancalcit0nin,itisnotrequiredf0rthat0feelandsalm0ncaIcitonin.ManysaIm0nc…     

O8肽的HPLC分析与制备研究

系统建立了化学合成小分子肽(08肽)的反相HPLC分离分析方法．考察了色谱填料种类、流动相组成及梯度条件对样品分离的影响．通过从分析型到半制备型分离线性放大过程中分离条件与分离效果的关系的探讨．建立了等度洗脱条件下较大规模地分离制备该小肽的方法试验结果表明：硅胶基质的色谱柱比聚合物基质的色谱柱更适合于分离该小肽,而粒径(5μm．10μm)对分离的影响不大;较缓的梯度条件可以明显改善分离,但所需分离时间延长一在制备分离中应综合考虑分离效果与运行时间的关系。     

A Simple Method for Cell Sheet Fabrication Using Mica Surfaces Grafted with Peptide Detergent A6K

Cell sheet technology is a very important strategy for scaffold‐free tissue engineering. In order to fabricate cell sheets by a simple method, peptide detergent A₆K was grafted on mica surfaces by dropping its aqueous solution at different concentrations on the surface. As revealed by surface topographical observation and water contact angle measurement, the most hydrophobic surface was obtained using peptide solution at the concentration of 0.2 mg · mL^?1. The peptide‐grafted mica surface was used to culture mouse preosteoblast cell MC3T3‐E1. After the cells reached confluence and the peptide was biodegraded, an intact cell sheet was peeled from the mica. This simple method does not need any non‐biological reagents or complicated procedures, and may have great potential in tissue engineering based on cell sheet technology.