-
近年来,核能与核技术的发展及广泛应用使人们暴露于辐射的风险增加。电离辐射引起生物基质的电离与激发,产生一系列的辐射生物效应,造成机体直接或间接的辐射损伤,最终可导致骨髓型、胃肠型和脑型等多种辐射病。辐射防护剂可有效降低辐射对细胞的有害影响,预防和减轻辐射损伤。多数辐射防护剂通过直接清除自由基或增强抗氧化能力发挥作用[1]。由于多肽在维持机体正常生理功能方面起着至关重要的作用,采用多肽类药物防治辐射损伤已越来越受关注。截至2015年,约有140种多肽类药物被用于临床试验,其中多种多肽及其类似物具有辐射损伤防护的潜在价值[2],我们对此进行综述。
多肽类辐射防护药物应用的研究进展
Application research progress in polypeptides radioprotective agents
-
摘要: 近年来,核能与核技术在工业、医药、科技、军事等领域的广泛应用使人们暴露于辐射的风险增加,而临床上仍缺乏安全、高效的辐射防护药物。功能多肽在体内担负着重要的调节功能,且多肽类药物具有靶向性、高特异活性、药品安全性高、易于改造修饰等优势。因此,多肽类辐射防护药物的相关研究较多。笔者将对多肽类辐射防护药物的特性和设计思路及其应用进行综述,旨在为多肽类辐射防护药物的研究奠定基础。Abstract: The potential risk of radiation exposure is increasing because of the widespread use of nuclear technologies in the fields of medicine, science, technology, and military and various industries. Moreover, safe and effective radioprotective agents are lacking. Polypeptides play a vital regulatory role in various living processes. Polypeptide drugs are highly selective, efficacious, and safe, and modifications are easy to incorporate for the optimization of peptide functionality. Hence, many studies on radioprotective polypeptides have been conducted. Here, we provide an overview of peptides as radioprotective agents, particularly their molecular characteristics, design ideas, and the specific therapeutic effects of potential radioprotective peptides, aiming to lay the groundwork for the research of radioprotective polypeptides.
-
Key words:
- Peptides /
- Radiation injuries /
- Radiation-protective agents
-
[1] Smith TA, Kirkpatrick DR, Smith S, et al. Radioprotective agents to prevent cellular damage due to ionizing radiation[J/OL]. J Transl Med, 2017, 15(1): 232[2020-11-15]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC5680756. DOI: 10.1186/s12967-017-1338-x. [2] Fosgerau K, Hoffmann T. Peptide therapeutics: current status and future directions[J]. Drug Discov Today, 2015, 20(1): 122−128. DOI: 10.1016/j.drudis.2014.10.003. [3] Angell Y, Holford M, Moos WH. Building on success: a bright future for peptide therapeutics[J]. Protein Pept Lett, 2018, 25(12): 1044−1050. DOI: 10.2174/0929866525666181114155542. [4] Lau JL, Dunn MK. Therapeutic peptides: historical perspectives, current development trends, and future directions[J]. Bioorg Med Chem, 2018, 26(10): 2700−2707. DOI: 10.1016/j.bmc.2017.06.052. [5] Burdelya LG, Krivokrysenko VI, Tallant TC, et al. An agonist of toll-like receptor 5 has radioprotective activity in mouse and primate models[J]. Science, 2008, 320(5873): 226−230. DOI: 10.1126/science.1154986. [6] Allen RJ, Mathew B, Rice KG. PEG-peptide inhibition of scavenger receptor uptake of nanoparticles by the liver[J]. Mol Pharmaceutics, 2018, 15(9): 3881−3891. DOI: 10.1021/acs.molpharmaceut.8b00355. [7] Bao WK, Holt LJ, Prince RD, et al. Novel fusion of GLP-1 with a domain antibody to serum albumin prolongs protection against myocardial ischemia/reperfusion injury in the rat[J/OL]. Cardiovasc Diabetol, 2013, 12: 148[2020-11-15]. https://cardiab.biomedcentral.com/articles/10.1186/1475-2840-12-148. DOI: 10.1186/1475-2840-12-148. [8] Rubin SJS, Tal-Gan Y, Gilon C, et al. Conversion of protein active regions into peptidomimetic therapeutic leads using backbone cyclization and cycloscan—how to do it yourself[J]. Curr Top Med Chem, 2018, 18(7): 556−565. DOI: 10.2174/1568026618666180518094322. [9] Rádis-Baptista G, Campelo IS, Morlighem JERL, et al. Cell-penetrating peptides (CPPs): from delivery of nucleic acids and antigens to transduction of engineered nucleases for application in transgenesis[J]. J Biotechnol, 2017, 252: 15−26. DOI: 10.1016/j.jbiotec.2017.05.002. [10] Toler J, Deputy S, Zakris E, et al. Cognitive dysfunction after cranial radiation for a brain tumor[J]. J Pediatr Infect Dis Soc, 2016, 5(1): 96−99. DOI: 10.1093/jpids/piv085. [11] Lu LN, Li ZL, Zuo YH, et al. Radioprotective activity of glutathione on cognitive ability in X-ray radiated tumor-bearing mice[J]. Neurol Res, 2018, 40(9): 758−766. DOI: 10.1080/01616412.2018.1476080. [12] Sharma UC, Sonkawade SD, Baird A, et al. Effects of a novel peptide Ac-SDKP in radiation-induced coronary endothelial damage and resting myocardial blood flow[J/OL]. Cardiooncology, 2018, 4: 8[2020-11-15]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6497419. DOI: 10.1186/s40959-018-0034-1. [13] Hajem N, Chapelle A, Bignon J, et al. The regulatory role of the tetrapeptide AcSDKP in skin and hair physiology and the prevention of ageing effects in these tissues—a potential cosmetic role[J]. Int J Cosmet Sci, 2013, 35(3): 286−298. DOI: 10.1111/ics.12046. [14] Daly MJ, Gaidamakova EK, Matrosova VY, et al. Small-molecule antioxidant proteome-shields in Deinococcus radiodurans[J/OL]. PLoS One, 2010, 5(9): e12570[2020-11-15]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC2933237. DOI: 10.1371/journal.pone.0012570. [15] Gaidamakova EK, Myles IA, McDaniel DP, et al. Preserving immunogenicity of lethally irradiated viral and bacterial vaccine epitopes using a radio- protective Mn2+-Peptide complex from Deinococcus[J]. Cell Host Microbe, 2012, 12(1): 117−124. DOI: 10.1016/j.chom.2012.05.011. [16] Gupta P, Gayen M, Smith JT, et al. MDP: A Deinococcus Mn2+-decapeptide complex protects mice from ionizing radiation[J/OL]. PLoS One, 2016, 11(8): e0160575[2020-11-15]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4976947. DOI: 10.1371/journal.pone.0160575. [17] Xu Y, Wang S, Shen MQ, et al. hGH promotes megakaryocyte differentiation and exerts a complementary effect with c-Mpl ligands on thrombopoiesis[J]. Blood, 2014, 123(14): 2250−2260. DOI: 10.1182/blood-2013-09-525402. [18] Long S, Wang GJ, Shen MQ, et al. dTMP-GH fusion protein therapy improves survival after radiation injury combined with skin-burn trauma in mice[J]. Radiat Res, 2019, 191(4): 360−368. DOI: 10.1667/RR5218.1. [19] Okunieff P, Cornelison T, Mester M, et al. Mechanism and modification of gastrointestinal soft tissue response to radiation: role of growth factors[J]. Int J Radiat Oncol Biol Phys, 2005, 62(1): 273−278. DOI: 10.1016/j.ijrobp.2005.01.034. [20] Zhang LR, Sun WM, Wang JJ, et al. Mitigation effect of an FGF-2 peptide on acute gastrointestinal syndrome after high-dose ionizing radiation[J]. Int J Radiat Oncol Biol Phys, 2010, 77(1): 261−268. DOI: 10.1016/j.ijrobp.2009.11.026. [21] Booth C, Booth D, Williamson S, et al. Teduglutide ([Gly2]GLP-2) protects small intestinal stem cells from radiation damage[J]. Cell Prolif, 2004, 37(6): 385−400. DOI: 10.1111/j.1365-2184.2004.00320.x. [22] Demori I, El Rashed Z, Corradino V, et al. Peptides for skin protection and healing in amphibians[J/OL]. Molecules, 2019, 24(2): 347[2020-11-15]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6359409. DOI: 10.3390/molecules24020347. [23] Zhang SY, Wang WJ, Peng Y, et al. Amelioration of radiation-induced skin injury by HIV-TAT-mediated protein transduction of RP-1 from Rana pleurade[J]. Int J Med Sci, 2014, 11(1): 44−51. DOI: 10.7150/ijms.7463. [24] Lee SW, Moon SY, Kim YH, et al. The use of recombinant human epidermal growth factor to promote healing for chronic radiation ulcer[J]. Int Wound J, 2007, 4(3): 216−220. DOI: 10.1111/j.1742-481X.2007.00332.x. [25] Ryu SH, Kim YH, Lee SW, et al. The preventive effect of recombinant human growth factor (rhEGF) on the recurrence of radiodermatitis[J]. J Radiat Res, 2010, 51(5): 511−517. DOI: 10.1269/jrr.10010. [26] Bernhardt SL, Gjertsen MK, Trachsel S, et al. Telomerase peptide vaccination of patients with non-resectable pancreatic cancer: a dose escalating phase Ⅰ/Ⅱ study[J]. Br J Cancer, 2006, 95(11): 1474−1482. DOI: 10.1038/sj.bjc.6603437. [27] Park JK, Kim Y, Kim H, et al. The anti-fibrotic effect of GV1001 combined with gemcitabine on treatment of pancreatic ductal adenocarcinoma[J/OL]. Oncotarget, 2016, 7(46): 75081−75093[2020-11-15]. http://www.oncotarget.com. DOI: 10.18632/oncotarget.12057. [28] Chen W, Shin KH, Kim S, et al. hTERT peptide fragment GV1001 demonstrates radioprotective and antifibrotic effects through suppression of TGF-β signaling[J]. Int J Mol Med, 2018, 41(6): 3211−3220. DOI: 10.3892/ijmm.2018.3566. [29] Holler M, Grottke A, Mueck K, et al. Dual targeting of Akt and mTORC1 impairs repair of DNA double-strand breaks and increases radiation sensitivity of human tumor cells[J/OL]. PLoS One, 2016, 11(5): e0154745[2020-11-15]. https://www.ncbi.nlm.nih.gov/pmc/articles/PMC4854483. DOI: 10.1371/journal.pone.0154745. [30] 李亚楠, 邹炯, 宋璐瑶, 等. 胶原三肽生物活性及其应用研究进展[J]. 食品工业科技, 2018, 39(3): 333−337. DOI: 10.13386/j.issn1002-0306.2018.03.064.
Li YN, Zou J, Song LY, et al. Bioactivities and applications of collagen tripeptides: a review[J]. Sci Technol Food Ind, 2018, 39(3): 333−337. DOI: 10.13386/j.issn1002-0306.2018.03.064.[31] Pollard JD, Quan S, Kang T, et al. Effects of copper tripeptide on the growth and expression of growth factors by normal and irradiated fibroblasts[J]. Arch Facial Plast Surg, 2005, 7(1): 27−31. DOI: 10.1001/archfaci.7.1.27. [32] He LX, Wang JB, Sun B, et al. Suppression of TNF-α and free radicals reduces systematic inflammatory and metabolic disorders: radioprotective effects of ginseng oligopeptides on intestinal barrier function and antioxidant defense[J]. J Nutr Biochem, 2017, 40: 53−61. DOI: 10.1016/j.jnutbio.2016.09.019.
计量
- 文章访问数: 9318
- HTML全文浏览量: 7330
- PDF下载量: 61