Study on Polyethylene Glycol Modification of RAGE Specific Antagonist Peptide

Feng Gao; Yiyun Huang; Nian Fang; Huiru Luo; Qing Zheng; Qingping Zeng

Study on Polyethylene Glycol Modification of RAGE Specific Antagonist Peptide

Feng Gao, Yiyun Huang, Nian Fang, Huiru Luo, Qing Zheng, Qingping Zeng

Abstract

Aim We want to increase the biological stability of short peptides by PEG modification. Methods Through connecting the maleimide group to one end of polyethylene glycol and adding a cysteine (Cys) to one end of the short peptide, the short peptide was finally modified by PEG through chemical bonds. We established a reverse high-performance liquid chromatography (RP-HPLC) detection method to detect the change of substances before and after the reaction; screened out the optimal detection method by orthogonal test; purified the modified short peptide by ultrafiltration; detected the reaction by infrared spectroscopy Changes in functional groups; tested the stability of RP-1 in rat plasma before and after modification. Result and discussion Through single factor test and orthogonal test, the pH in the reaction was 6, reaction temperature was 25 ?C, reaction time was 1H, and reaction ratio was PEG: RP-1C 1:1.5. The solution does not contain RP-1C after ultrafiltration. Peripheral plasma stability testing found that the modified short peptides greatly enhanced the stability. Conclusion Through experiments, we found the best conditions for the modification of short peptides, purification methods, and the stability of the modified short peptides was greatly improved.

Keywords

Peptide; Polyethylene glycol; Reversed-phase high performance liquid chromatography; Orthogonal test.

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References

Lane, CA, Hardy J, Schott JM. Alzheimer's disease. Eur J Neurol. 2018, 25, 59-70.

Jia J, Wang F, Wei C, Zhou A, Jia X et al. The prevalence of dementia in urban and rural areas of China. Alzheimers Dement 2014, 10, 1-9.

Jia J, Wei C, Chen S, Li F, Tang Y et al. The cost of Alzheimer's disease in China and re-estimation of costs worldwide. Alzheimers Dement. 2018, 14, 483-491.

Bierhaus A, Humpert PM, Morcos M, Wendt T, Chavakis T et al. Understanding RAGE, the receptor for advanced glycation end products. J Mol Med. 2005;83: 876-886.

Deane R, Singh I, Sagare AP, Bell RD, Ross NT et al. A multimodal RAGE-specific inhibitor reduces amyloid beta-mediated brain disorder in a mouse model of Alzheimer disease. J Clin Invest. 2012;122: 1377-1392.

Galasko D, Bell J, Mancuso JY, Kupiec JW, Sabbagh MN et al. Clinical trial of an inhibitor of RAGE-Abeta interactions in Alzheimer disease. Neurology. 2014;82: 1536-1542.

Hong Y, Shen C, Yin Q, Sun M, Ma Y, Liu X. Effects of RAGE-Specific Inhibitor FPS-ZM1 on Amyloid-beta Metabolism and AGEs-Induced Inflammation and Oxidative Stress in Rat Hippocampus. Neurochem Res. 2016;41: 1192-1199.

Yan SD, Chen X, Fu J, Chen M, Zhu H, et al. RAGE and amyloid-beta peptide neurotoxicity in Alzheimer's disease. Nature 1996, 382, 685-691.

Cai C, Dai X, Zhu Y, Lian M, Xiao F et al. A specific RAGE-binding peptide biopanning from phage display random peptide library that ameliorates symptoms in amyloid beta peptide-mediated neuronal disorder. Appl Microbiol Biotechnol. 2016;100: 825-835.

Abuchowski A, van Es T, Palczuk NC, Davis FF. Alteration of immunological properties of bovine serum albumin by covalent attachment of polyethylene glycol. J Biol Chem. 1977;252: 3578-3581.

Abuchowski A, McCoy JR, Palczuk NC, van Es T, Davis FF. Effect of covalent attachment of polyethylene glycol on immunogenicity and circulating life of bovine liver catalase. J Biol Chem. 1977;252: 3582-3586.

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