多肽介导的核酸药物递送系统研究进展

核酸药物作为新型基因治疗药物备受关注,但生物学稳定性差、易被体内核酸酶降解、生物利用度低、靶组织内聚集浓度低等是制约其发展的主要因素。新的药物递送技术的快速发展在一定程度上解决了核酸药物的稳定性及靶向递送问题,极大地推动了核酸药物的研发进展。尤其是多肽蛋白类递送载体,已成为核酸药物递送系统研究领域的热点之一。介绍核酸药物递送载体多肽修饰的两种主要方式——共价缀合和非共价络合,重点综述近年来多肽缀合物和复合物以及多肽修饰的载体在核酸药物递送系统中的应用研究,探讨多肽介导的核酸药物递送系统在应用中存在的问题,为新型核酸药物递送系统研发提供参考。     

多肽药物研究进展

人体内存在各种各样的天然多肽,它们参与调控各种生理功能,在临床应用上具有非常重要的开发价值。目前全球药物市场上有60～70个多肽药物,更多的多肽药物处在各级临床试验、临床前试验和实验室研究阶段。很多多肽药物以G蛋白偶联受体为靶点。传统的化学合成也仍然是开发多肽药物最主要的手段。然而,我们在多肽药物开发方面仍面临各种挑战,不仅要解决传统问题如不稳定,易降解,难穿越细胞膜,而且也要进一步降低生产成本,完善大批量生产工艺技术。尤其是多肽药物的口服生物利用度问题,一直是我们面临的最大的挑战和决定市场的关键因素。随着在现代技术及其它方面不断取得进展,多肽药物将具有更加广阔的前景。在新一代受体靶向药物研究中,多肽更被作为一种有效的药物载体,通过细胞表面受体将药物传递到特定细胞,达到提高特异性,减少副作用的目的。     

多肽类药物有关物质研究的探讨

多肽类药物一般需要通过注射给药,有关物质检查是控制药品安全性的重要指标。由于多肽类药物的自身特点,如何进行多肽药物的有关物质研究是一个很值得探讨的问题。笔者结合多肽药物的特性和自身工作实践,总结了多肽药物有关物质研究中常见的问题,并提出了自己的见解。     

浅析多肽类药物常用的分析方法

多肽类药物作为药物研究的新课题越来越多地受到了人们的关注,其分析手段的研究也成为了最活跃、发展最迅速的领域之一。目前,建立灵敏、准确、操作简便的多肽类药物分析方法面临着诸多挑战和机遇。本文中,作者首先介绍了几种常见的多肽类药物及其主要优势,进而介绍了几种备受关注的多肽类药物的分析方法。     

蝎毒抗癌多肽对大肠癌LoVo细胞的影响

目的探讨东亚钳蝎毒抗癌多肽对大肠癌LoVo细胞的影响及其与多种化疗药物的协同作用。方法采用MTT法(噻唑蓝比色试验)测定该抗癌多肽单独及与化疗药物协同对LoVo细胞的增殖抑制作用。结果蝎毒抗癌多肽可抑制LoVo细胞增殖,并且低浓度的蝎毒抗癌多肽与化疗药物协同,可产生较强的抑制细胞增殖的作用。结论蝎毒抗癌多肽具有直接的抗肿瘤作用,并且具有增强化疗药物作用的功效。     

多肽蛋白质类药物微球制备方法研究进展

多肽蛋白质药物在人类疾病治疗中的作用日趋重要,开发多肽蛋白质类药物的微球给药系统,防止药物在体内很快降解,将药物有效递送至人体相应部位,这对多肽蛋白质药物的的开发和利用特别有意义。目前,微球制备中常用的方法有液中干燥法、喷雾干燥法、相分离法和乳化交联法等。     

蛋白质和多肽类药物分子化学修饰的研究进展

目的蛋白质、多肽等药物分子免疫原性和毒副反应的存在及体内作用时间短等问题限制了其应用 ,这可以通过化学修饰部分或全部加以克服。随着生物大分子构效关系逐步得到揭示 ,生物大分子化学修饰的研究迅速发展。此文对蛋白质、多肽等药物分子化学修饰的国内外研究现状和发展动态加以评述 ,包括化学修饰原理、化学修饰方法、修饰后药物分子的应用等     

基于德尔菲法构建《中国妊娠期药物风险评估专家共识》

目的:基于德尔菲法构建《中国妊娠期药物风险评估专家共识》,为进一步开展妊娠期药物风险评估研究提供方法学基础.方法:参考妊娠期药物风险评估研究相关文献,撰写《中国妊娠期药物风险评估专家共识》,并设计专家咨询问卷.选取北京、上海等省市51名专家,应用德尔菲法进行两轮专家咨询,对《中国妊娠期药物风险评估专家共识》的内容进行修...     

多肽药物的发展现状

随着生物技术与多肽合成技术的日臻成熟．越来越多的多肽药物被开发并应用于临床。因适应证广、安全性高且疗效显著．多肽药物目前已广泛应用于肿瘤、肝炎、糖尿病、艾滋病等疾病的预防、诊断和治疗,具有广阔的开发前景。简介多肽药物的来源与特点及制备方法．重点综述国内外多肽药物的研发概况、国外近年获准上市的主要多肽药物和我国自主研发并进入临床研究的主要多肽药物,旨在为该类新药的研发提供参考。     

多肽在生物医药和诊断试剂中的应用

简要介绍多肽作为药物及诊断试剂的特点、主要的筛选途径及国内外研究概况。系统介绍多肽在疫苗、抗肿瘤、抗病毒及抗菌药物、导向药物、细胞因子模拟肽、诊断试剂等领域的研究及应用情况     

固相法在多肽合成领域的应用

综述近年来固相多肽合成方法在聚合物载体、连接分子、保护基、缩合方法和切割条件等方面的应用进展。多肽的全合成不仅具有重要的理论意义，而且具有重要的应用价值。特别是固相多肽合成方法的创立和发展，是多肽合成领域的一个重大突破，对化学、生化、医药、免疫及分子微生物学等领域都起了巨大的推动作用。     

多肽类药物口服吸收的研究进展

多肽类药物对癌症、自身免疫性疾病具有良好的治疗前景。目前，市售肽类制剂以注射剂为主，频繁的注射给患者造成很大的痛苦。口服作为一种方便、顺应性好的给药途径，日益成为研究焦点；然而肽类药物口服受消化道屏障限制，生物利用度低，半衰期短，制约了它的发展。提高多肽类药物口服生物利用度的研究工作业已展开。本文综述了限制肽类药物口服吸收的主要影响因素及针对性的解决策略。     

Progress with peptide scanning to study structure-activity relationships: the implications for drug discovery

ABSTRACT

Introduction: Peptides have gained renewed interest as candidate therapeutics. However, to bring them to a broader clinical use, challenges such as the rational optimization of their pharmacological properties remain. Peptide scanning techniques offer a systematic framework to gain information on the functional role of individual amino acids of a peptide. Due to progress in mastering new chemical synthesis routes targeting amino acid backbone, they are currently diversified. Structure-activity relationship (SAR) analyses such as alanine- or enantioneric- scanning can now be supplemented by N-substitution, lactam cyclisation- or aza-amino scanning procedures addressing not only SAR considerations but also the peptide pharmacological properties.

Areas covered: This review highlights the different scanning techniques currently available and illustrates how they can impact drug discovery.

Expert opinion: Progress in peptide scanning techniques opens new perspectives for peptide drug development. It comes with the promise of a paradigm change in peptide drug design in which peptide drugs will be closer to the parent peptides. However, scanning still remains assimilable to a trial and error strategy that could benefit from being combined with specific in silico approaches that start reaching maturity.     

MAGE-3多肽诱导特异性T细胞对人肝癌细胞株的杀伤作用

目的观察MAGE-3多肽特异性T细胞的诱导和对人肝癌细胞株HepG 2细胞的作用。方法合成MAGE-3多肽271～279肽段,合成肽诱导培养的淋巴细胞与人肝癌细胞株HepG 2细胞共同混合培养,观察T细胞对肿瘤细胞的结合;MAGE-3多肽诱导肝癌患者外周淋巴细胞,四聚体方法检验MAGE-3多肽特异性T细胞的诱导。结果MAGE-3多肽特异性淋巴细胞与对人肝癌细胞株HepG 2细胞有明显的聚集、粘附和可能的攻击作用;肝癌患者外周淋巴细胞中特异性T细胞频数提高。结论MAGE-3多肽可以诱导肿瘤患者特异性T细胞,诱导的特异性T细胞对人肝癌细胞株HepG 2细胞可能有杀伤作用,显示MAGE-3多肽可作为肝癌生物治疗特异性表位肽候选多肽。     

Peptidic Inhibitors for in Vitro Pentamer Formation of Human Papillomavirus Capsid Protein L1

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新抗菌靶点肽去甲酰基酶抑制剂的研究进展

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用多中心合成方法快速、同步合成多肽

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cDNA sequence and in vitro folding of GsMTx4, a specific peptide inhibitor of mechanosensitive channels.

The peptide GsMTx4 from the tarantula venom (Grammostola spatulata) inhibits mechanosensitive ion channels. In this work, we report the cDNA sequence encoding GsMTx4. The gene is translated as a precursor protein of 80 amino acids. The first 21 amino acids are a predicted signal sequence and the C-terminal residues are a signal for amidation. An arginine residue adjacent to the N-terminal glycine of GsMTx4 is the cleavage site for release. The resulting peptide is 34 amino acids in length with a C-terminal phenylalanine and not a serine-alanine previously identified [J. Gen. Physiol. 115 (2000) 583]. We chemically synthesized this peptide and folded it in 0.1 M Tris, pH 7.9 with oxidized/reduced glutathione (1/10). Properties of the synthetic peptide were identical to the wild type for high performance liquid chromatography (HPLC), mass spectrometry, CD, and NMR. We also cloned GsMTx4 in a thioredoxin fusion protein system containing six histidines. Nickel affinity columns allowed rapid purification and folding occurred in conditions described above with 0.5 M guanidiniumHCl present. Thrombin cleavage liberated GsMTx4 with three extra amino acids at the N-terminus. The retention time in HPLC analysis and the CD spectrum was similar to wild type. Both the synthetic and cloned peptides were active in the patch clamp assay.     

A rational nomenclature for naming peptide toxins from spiders and other venomous animals

Molecular toxinology research was initially driven by an interest in the small subset of animal toxins that are lethal to humans. However, the realization that many venomous creatures possess a complex repertoire of bioactive peptide toxins with potential pharmaceutical and agrochemical applications has led to an explosion in the number of new peptide toxins being discovered and characterized. Unfortunately, this increased awareness of peptide-toxin diversity has not been matched by the development of a generic nomenclature that enables these toxins to be rationally classified, catalogued, and compared. In this article, we introduce a rational nomenclature that can be applied to the naming of peptide toxins from spiders and other venomous animals.     

Proteome of monocled cobra (Naja kaouthia) venom and potent anti breast cancer peptide from trypsin hydrolyzate of the venom protein

Anticancer peptide is one of the target in the development of new anticancer drug. Bioactive peptide can be originated from isolated free peptide or produced by hydrolysis of protein. Protein is the main component of Naja kaouthia venom, and due to the toxicity of the venom, it can be assessed as the source of anticancer peptides. This study aims to characterize the venom protein and to identify peptides from the snake venom of N. kaouthia as anticancer. Proteome analysis was employed trypsin hydrolysis of N. kaouthia venom protein completed with HRMS analysis protein database query. Preparative tryptic hydrolysis of the protein followed by reverse-phased fractionation and anti breast cancer activity testing were performed to identify the potent anticancer from the hydrolysate. Proteomic analysis by high-resolution mass spectrometry revealed that there are 20 enzymatic and non-enzymatic proteins in N. kaouthia venom. The 25% methanol peptide fraction had the most active anticancer activity against MCF-7 breast cancer cells and showed promising selectivity (selectivity index = 12.87). Amino acid sequences of eight peptides were identified as potentially providing anticancer compounds. Molecular docking analysis showed that WWSDHR and IWDTIEK peptides gave specific interactions and better binding affinity energy with values of −9.3 kcal/mol and −8.4 kcal/mol, respectively. This study revealed peptides from the snake venom of N. kaouthia became a potent source of new anticancer agents.