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Identification and Design of a Next-Generation Multi Epitopes Bases Peptide Vaccine Candidate Against Prostate Cancer: An In Silico Approach.
Cell Biochemistry and Biophysics ( IF 2.6 ) Pub Date : 2020-04-28 , DOI: 10.1007/s12013-020-00912-7
Prasanta Patra 1 , Manojit Bhattacharya 1, 2 , Ashish Ranjan Sharma 2 , Pratik Ghosh 1 , Garima Sharma 3 , Bidhan Chandra Patra 1 , Bidyut Mallick 4 , Sang-Soo Lee 2 , Chiranjib Chakraborty 2, 5
Affiliation  

Prostate cancer (PCa) is the second most diagnosed cancer in men and ranked fifth in overall cancer diagnosis. During the past decades, it has arisen as a significant life-threatening disease in men at an older age. At the early onset of illness when it is in localized form, radiation and surgical treatments are applied against this disease. In case of adverse situations androgen deprivation therapy, chemotherapy, hormonal therapy, etc. are widely used as a therapeutic element. However, studies found the occurrences of several side effects after applying these therapies. In current work, several immunoinformatic techniques were applied to formulate a multi-epitopic vaccine from the overexpressed antigenic proteins of PCa. A total of 13 epitopes were identified from the five prostatic antigenic proteins (PSA, PSMA, PSCA, STEAP, and PAP), after validation with several in silico tools. These epitopes were fused to form a vaccine element by (GGGGS)3 peptide linker. Afterward, 5, 6-dimethylxanthenone-4-acetic acid (DMXAA) was used as an adjuvant to initiate and induce STING-mediated cytotoxic cascade. In addition, molecular docking was performed between the vaccine element and HLA class I antigen with the low ACE value of −251 kcal/mol which showed a significant binding. Molecular simulation using normal mode analysis (NMA) illustrated the docking complex as a stable one. Therefore, this observation strongly indicated that our multi epitopes bases peptide vaccine molecule will be an effective candidate for the treatment of the PCa.



中文翻译:

鉴定和设计针对前列腺癌的下一代多表位碱基肽疫苗候选对象:计算机方法。

前列腺癌(PCa)是男性中诊断第二多的癌症,在整体癌症诊断中排名第五。在过去的几十年中,它已成为老年男性中一种严重的威胁生命的疾病。在疾病以局部形式出现的早期发作时,对这种疾病进行放射和外科治疗。在不利情况下,雄激素剥夺疗法,化学疗法,激素疗法等被广泛用作治疗成分。但是,研究发现,应用这些疗法后会出现多种副作用。在当前的工作中,几种免疫信息学技术被用于从过表达的PCa抗原蛋白中配制多表位疫苗。从五个前列腺抗原蛋白(PSA,PSMA,PSCA,STEAP和PAP)中总共鉴定出13个表位,经过几个in silico工具验证后。这些表位通过(GGGGS)融合形成疫苗元件3个肽接头。之后,使用5,6-二甲基黄嘌呤酮-4-乙酸(DMXAA)作为佐剂来引发和诱导STING介导的细胞毒性级联反应。此外,在疫苗元件和HLA I类抗原之间进行了分子对接,其ACE值为-251 kcal / mol,具有很强的结合力。使用正态模式分析(NMA)进行的分子模拟表明,对接复合物是一种稳定的复合物。因此,该观察结果强烈表明我们的多表位碱基肽疫苗分子将是治疗PCa的有效候选者。

更新日期:2020-04-28
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