修饰氨基酸的人干扰素-α2b聚乙二醇化增加循环半衰期和抗增殖活性

IF 2.8 3区综合性期刊 Q2 MULTIDISCIPLINARY SCIENCES

Journal of Taibah University for Science Pub Date : 2023-11-09 DOI:10.1080/16583655.2023.2272365

Syeda Kiran Shahzadi, Muhammad Abdul Qadir, Nasir Mahmood, Mahmood Ahmed

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引用次数: 0

摘要

干扰素-α2b (IFN-α2b)被用作治疗各种类型癌症的药物。在目前的研究中，我们制备了修饰形式的人INF-α2b，以研究氨基酸取代对干扰素受体结合和抗增殖活性的影响。修饰后的人IFN-α2b蛋白被聚乙二醇化，以增加其体内循环半衰期。用mpeg -丙醛琥珀酸酯(20和40 kDa)进行n端聚乙二醇化。由于这些修饰，与野生型IFN-α2b (0.125 ng)相比，修饰R(23)H的IFN-α2b在0.062 ng时达到IC50。与野生型IFN-α2b相比，聚乙二醇化IFN-α2b及其修饰形式的水动力体积和血清滞留时间(高达62小时)增加。然而，与野生型相比，聚乙二醇化IFN-α2b的大小增加，聚乙二醇化IFN对HepG2细胞系的抗增殖活性降低(高达4.7%)。

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PEGylation of human interferon-α2b with modified amino acids increases circulation half-life and antiproliferative activity

Interferon-α2b (IFN-α2b) is used as a therapeutic agent against various types of cancer. In the current research, modified forms of human INF-α2b were produced to investigate the effect of amino acid substitutions on binding to the interferon receptor and antiproliferative activity. The resulting modified human IFN-α2b proteins were PEGylated to increase their in vivo circulation half-life. N-terminal PEGylation was performed using mPEG-propionaldehyde succinate (20 and 40 kDa). As a result of these modifications, IFN-α2b with modification R(23)H achieved IC50 at 0.062 ng as compared to wild type IFN-α2b (0.125 ng). PEGylation of IFN-α2b and its modified forms resulted in an increase in hydrodynamic volume and serum retention time (up to 62 h) compared to wild type IFN-α2b (4 h). However, the antiproliferative activities of PEGylated IFN against HepG2 cell line were decreased (up to 4.7%) with an increase in PEGylated IFN-α2b size as compared to the wild type.

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来源期刊

Journal of Taibah University for Science MULTIDISCIPLINARY SCIENCES-

CiteScore

6.60

自引率

6.10%

发文量

102

审稿时长

19 weeks

期刊介绍： Journal of Taibah University for Science (JTUSCI) is an international scientific journal for the basic sciences. This journal is produced and published by Taibah University, Madinah, Kingdom of Saudi Arabia. The scope of the journal is to publish peer reviewed research papers, short communications, reviews and comments as well as the scientific conference proceedings in a special issue. The emphasis is on biology, geology, chemistry, environmental control, mathematics and statistics, nanotechnology, physics, and related fields of study. The JTUSCI now quarterly publishes four issues (Jan, Apr, Jul and Oct) per year. Submission to the Journal is based on the understanding that the article has not been previously published in any other form and is not considered for publication elsewhere.