蛋白药物的聚乙二醇定点修饰策略与最佳位点

聚乙二醇修饰是一种改善蛋白质药物临床药效行之有效的方法。聚乙二醇修饰具有延长蛋白质药物在体内的半衰期、降低免疫原性和延缓蛋白酶降解、提高稳定性和溶解性等优点。而聚乙二醇的定点修饰由于能够获得均一性和高活性保留率的产物,并能提高产率,已经引起了广泛关注。综述了近年来聚乙二醇定点修饰蛋白质药物方面的研究进展,着重介绍了聚乙二醇定点修饰的策略及最佳修饰位点,并对聚乙二醇定点修饰技术的发展趋势进行了展望。     

天然多糖作为蛋白质药物化学修饰剂的研究进展

蛋白质工程和基因工程技术的迅速发展迎来了蛋白质类药物的新时代。然而,蛋白质药物稳定性差、体内半衰期短且常具有免疫原性,极大限制了其临床治疗效果。目前,研究人员发展了多种策略改造蛋白质分子,其中以利用聚合物进行化学修饰发展最为迅速,并推动多种聚乙二醇修饰的蛋白质药物上市。天然多糖是构成生命体的大分子物质之一,与聚乙二醇类似,高相对分子质量的多糖可以赋予蛋白质类药物延长的半衰期、更高稳定性及更低免疫原性。另一方面,多糖修饰还可以提高蛋白质药物的靶向性、入胞能力,协同发挥多糖自身的抗凝、抗肿瘤和抗氧化等活性。本文对蛋白质药物的多糖修饰研究进展进行综述。     

蛋白质药物的聚乙二醇修饰

聚乙二醇被广泛应用于蛋白质药物的化学修饰,修饰后的蛋白质药物的性质发生多方面变化,如:增加了此类药物的溶解度和稳定性,耐酶水解的能力增强,减弱或消除免疫原性,增加药物在体内的半衰期等。近年来,聚乙二醇修饰剂的种类和修饰方法发展较快,蛋白质分子上的氨基、巯基、羧基均成为化学修饰的研究对象。本文综述了聚乙二醇修饰的原理与方法,修饰方法的比较与优化,修饰后产品的鉴定与检测。     

蛋白质的聚乙二醇修饰及其在医药研究中的应用

生物工程的发展使许多蛋白质类药物的广泛使用成为可能,但仍存在免疫原性、毒副反应等问题.蛋白质的化学修饰从某种程度上克服了上述不足。如消除抗原性、延长体内作用时间等,从而提高了药物蛋白质的效率.文章主要介绍聚乙二醇对蛋白质的修饰及其在抗肿瘤蛋白质、调节代谢酶类、溶血栓因子、抗炎症酶及血浆蛋白研究中的一些进展.     

多肽表面修饰脂质体药物递送系统

本文通过查阅并归纳近几年相关文献,较为系统地概述了靶向活性多肽、细胞穿膜肽和靶向细胞穿膜肽等多肽表面修饰脂质体药物递送系统(drug delivery system, DDS)的研究进展。经不同活性多肽表面修饰,或可增强脂质体DDS的靶向性,或可提高药物的细胞摄取率和生物利用度。总之,多肽表面修饰的脂质体在新型DDS研究及应用中具有良好的前景。     

酶分子化学修饰研究进展

酶是高效生物催化剂,在工业和临床医药上应用广泛。但由于酶是蛋白质,稳定性差,且在生物体内有较强的免疫原性,因而严重制约了其应用。对酶分子进行化学修饰是提高其稳定性和降低免疫原性的有效途径。简要介绍几种改进酶催化特性的方法、酶分子修饰效果的分析与评价、酶通过化学修饰获得的新性质及其原理、酶化学修饰的研究动态等。     

聚乙二醇对蛋白质类药物的修饰

随着基因工程技术的发展,蛋白质类药物的应用越来越受到人们的青睐。但蛋白质类药物具有血浆半衰期较短、有一定的免疫原性等不足之处,在一定程度上限制了其临床应用。由于聚乙二醇(PEG)具有与蛋白质相容的特性,用其对蛋白质类药物进行化学修饰已经成为医学和生物工程领域的热门课题。本文重点介绍了PEG的特性以及应用其修饰蛋白质类药物的原理和存在的一些问题。     

聚乙二醇化修饰对蛋白多肽药物药代动力学的影响

聚乙二醇（PEG）化修饰在生物制药领域被认为是改变蛋白多肽类药物生物、理化性质的最佳方法之一。众多研究表明,PEG化后的蛋白多肽在生物体内的药代动力学行为有了很大改变,主要表现在：吸收相半衰期及消除相半衰期延长．血药峰浓度提高,达峰时间滞后,表观分布容积变小,免疫反应性减弱,血浆清除减慢。这些变化极大地改善了蛋白多肽药物在机体内清除快、免疫原性高、有效血药浓度持续时间短、需频繁给药等缺点。聚乙二醇化修饰为生物制药领域开辟了新的天地。     

综述与专论: 适配体功能化外泌体在肿瘤靶向治疗中的应用

传统的肿瘤治疗方法因缺乏足够的靶向性而会产生严重的毒副作用。外泌体（exosome）是一种天然的纳米囊泡,参与细胞间的信息传递,并且作为药物递送载体具有出色的性能优势,包括低免疫原性、低毒性和能够穿越天然屏障等特点。然而以外泌体为载体的药物递送系统的靶向能力仍有不足。适配体（aptamer）是一类化学合成的单链核酸分子,具有分子质量小、易于修饰和免疫原性低等特点,可作为亲和性配体与靶向分子特异性结合。通过在外泌体表面修饰适配体,药物可以被精确递送到肿瘤细胞发生部位,从而实现对肿瘤的靶向治疗,提高肿瘤治疗效果,减少毒副作用。本篇综述将重点讨论适配体功能化外泌体药物靶向递送系统在各种肿瘤治疗方面的应用,并对其未来的挑战和机遇进行阐述。     

多肽固相合成的研究进展

多肽固相化学合成法是蛋白质研究领域非常重要的研究方法之一,主要可以分为Boc方法和Fmoc方法,在生物药物、蛋白质工程、免疫学等研究中得到了广泛的应用。该文论述了多肽固相合成法的原理,比较了两种典型合成方法的优缺点,介绍了适用于该方法的多肽种类,提出了多肽合成过程中存在的问题与解决策略,最后展望了多肽合成法的应用前景,以供相关领域的研究人员参考。     

Entwicklungsgeschichte und Ultrastruktur von Pollenkitt und Exine bei nahe verwandten entomophilen und anemophilen Angiospermensippen derAlismataceae,Liliaceae, Juncaceae,Cyperaceae, Poaceae undAraceae

Some closely related members of the monocotyledonous familiesAlismataceae, Liliaceae, Juncaceae, Cyperaceae, Poaceae andAraceae with variable modes of pollination (insect- and wind-pollination) were studied in relation to the ultrastructure of pollenkitt and exine (amount, consistency and distribution of pollenkitt on the surface of pollen grains). The character syndromes of pollen cementing in entomophilous, anemophilous and intermediate (ambophilous or amphiphilous) monocotyledons are the same in principal as in dicotyledons. Comparing present with former results one can summarize: 1) The pollenkitt is always produced in the same manner by the anther tapetum in all angiosperm sub-classes. 2) The variable stickiness of entomophilous and anemophilous pollen always depends on the particular distribution and consistency of the pollenkitt, but not its amount on the pollen surface. 3) The mostly dry and powdery pollen of anemophilous plants always contains a variable amount of inactive pollenkitt in its exine cavities. 4) A step-by step change of the pollen cementing syndrome can be observed from entomophily towards anemophily. 5) From the omnipresence of pollenkitt in all wind-pollinated angiosperms studied one can conclude that the ancestors of anemophilous angiosperms probably have been zoophilous (i.e. entomophilous) throughout.

     

Identification and Characterization of the First Equine Parainfluenza Virus 5

正Dear Editor,Parainfluenza virus 5 (PIV5), known as canine parainfluenza virus in the veterinary field, is a negative-sense,nonsegmented, single-stranded RNA virus belonging to the Paramyxoviridae family (Chen 2018). The virus was first reported in primary monkey kidney cells in 1954 (Hsiung1972), then it has been frequently discovered in various     

Pathogenic Characterization and Full Length Genome Sequence of a Reassortant Infectious Bursal Disease Virus Newly Isolated in Pakistan

<正>Dear Editor,Infectious bursal disease (IBD) is one of the most important diseases of the poultry. The IBD virus (IBDV), a nonenveloped virus belonging to the Birnaviridae family with a genome consisting of two segments of double-stranded RNA (segments A and B), targets B lymphocytes of bursa of Fabricious leading to immunosuppression. In Pakistan,poultry farming is the second biggest industry and IBD is the second biggest disease threating the poultry sector.However, there is limited genome information of IBDV     

Similar aerosol emission rates and viral loads in upper respiratory tracts for COVID-19 patients with Delta and Omicron variant infection

Highlights
1 Aerosol emission rates of Delta or Omicron patients were similar.
2 Viral loads in upper respiratory tract of Alpha, Delta and Omicron patients were similar.
3 Viral loads in upper respiratory tract of vaccinated or unvaccinated Delta patients had no difference.     

Recombinant human interferon-α1b inhibits SARS-CoV-2 better than interferon-α2b in vitro

Highlights
1) A comprehensive evaluation method for anti-SARS-CoV-2 drugs was established based on RT-qPCR, TCID₅₀ method, and immunofluorescence.
2) A significant antiviral effect of rHuIFN-α1b was shown with EC₅₀=0.12 IU/mL in Vero cells and EC₅₀=0.52 IU/mL in Calu-3 cells, which was better than rHuIFN-α2b (EC₅₀=0.25 IU/mL in Vero cells and EC₅₀=2.48 IU/mL in Calu-3 cells).
3) rHuIFN-α1b has a good potential in the application of anti-COVID-19 therapy.     

Continued antigenic variation of highly pathogenic avian influenza A (H7N9) virus in laying hens in China, 2020–2021

Highlights
1. 13 strains of H7N9 viruses from laying hens in 2020 and 2021 were identified.
2. H7N9 viruses in China comprised at least 11 genotypes.
3. H7N9 viruses are high pathogenic in chickens, not in ducks.
4. The most H7N9 viruses cross-reacted poorly with H7-Re3 antiserum.
5. The H7-Re3 vaccine was unable to prevent H7N9 infection.