Synthesis of Tetrapeptides and Screening of their Antioxidant Properties

Author(s): Rani Maharani*, Dadan Sumiarsa, Achmad Zainuddin, Nuruzzahra Ammatillah, Ace T. Hidayat, Desi Harneti, Nurlelasari, Unang Supratman.

Journal Name: Current Bioactive Compounds

Volume 15 , Issue 6 , 2019

Become EABM
Become Reviewer

Graphical Abstract:


Abstract:

Background: Tetrapeptide Pro-Ala-Gly-Tyr (PAGY) is an antioxidant peptide that was isolated by Nikoo et al. (2014) from hydrolysate of skin gelatin of amur sturgeon fish (Acipenser schrenckii). This research aims to synthesize PAGY and its analogues by a solid-phase method, and to screen their antioxidant activities.

Methods: PAGY and its analogues, namely, Pro-Ser-Gly-Tyr (PSGY), Pro-Ala-Phe-Tyr (PAFY), Pro- Phe-Phe-Tyr (PFFY) and Pro-Ala-Ile-Tyr (PAIY), were synthesized via a solid phase peptide synthesis method with the Fmoc/t-Bu strategy. The synthesis was undertaken on 2-chlorotritylchloride resin as solid support, and all coupling reactions were facilitated by a combination of HBTU and HOBt reagents. All peptides were cleaved from the resin by using 95% TFA in water.

Results: Through the solid-phase synthesis method, all peptides were obtained in 50-85% yields. Pure peptides were analysed by analytical RP-HPLC, and were characterized by HR-TOF-ESI-MS and 1HNMR. DPPH inhibition assay was applied to all of the peptides with IC50 of 1.750; 1.116; 1.177 ;1.437; and 1.642 mg/mL for PAGY, PSGY, PAFY, PFFY, and PAIY, respectively.

Conclusion: PAGY and its four analogs were successfully synthesized by solid-phase method. PSGY compound was found to have the highest activity of all in DPPH assay.

Keywords: Antioxidant, tetrapeptide, solid phase peptide synthesis, PAGY, PAFY, PAIY, PFFY, PSGY.

[1]
Fosgerau, K.; Hoffmann, T. Peptide therapeutics: Current status and future directions. Drug Discov. Today, 2015, 20(1), 122-128.
[http://dx.doi.org/10.1016/j.drudis.2014.10.003] [PMID: 25450771]
[2]
Sewald, N.; Jakubke, H-D. Peptides: Chemistry and Biology; John Wiley & Sons: New Jersey, 2015.
[3]
Mollica, A.; Pinnen, F.; Azzurra, S.; Costante, R. The evolution of peptide synthesis: From early days to small molecular machines. Curr. Bioact. Compd., 2013, 9, 184-202.
[http://dx.doi.org/10.2174/157340720903140119151919]
[4]
Kim, S-K. Marine Proteins and Peptides: Biological Activities and Applications; John Wiley & Sons: New Jersey, 2013.
[http://dx.doi.org/10.1002/9781118375082]
[5]
de Castro, R.J.S.; Sato, H.H. Biologically active peptides: Processes for their generation, purification and identification and applications as natural additives in the food and pharmaceutical industries. Food Res. Int., 2015, 74, 185-198.
[http://dx.doi.org/10.1016/j.foodres.2015.05.013] [PMID: 28411983]
[6]
Stefanucci, A.; Uysal, S.; Ceylan, R.; Zengin, G. Natural occurring β-peptides: A fascinating world of bioactive molecules. Curr. Bioact. Compd., 2017, 14(1), 3-8.
[7]
Uhlig, T.; Kyprianou, T.; Martinelli, F.G.; Oppici, C.A.; Heiligers, D.; Hills, D.; Calvo, X.R.; Verhaert, P. The emergence of peptides in the pharmaceutical business: From exploration to exploitation. EuPA Open Proteom., 2014, 4, 58-69.
[http://dx.doi.org/10.1016/j.euprot.2014.05.003]
[8]
Xiong, Y.L. Antioxidant peptides. . In: Bioactive proteins and peptides as functional foods and nutraceuticals; Mine, Y.; Li‐Chan, E.; Jiang, B., Eds.; Blackwell Publishing Ltd.: Oxford, 2010, pp. 29-42.
[9]
Yu, X.; Wang, W.; Yang, M. Antioxidant activities of compounds isolated from Dalbergia Odorifera T. Chen and their inhibition effects on the decrease of glutathione level of rat lens induced by UV irradiation. Food Chem., 2007, 104, 715-720.
[http://dx.doi.org/10.1016/j.foodchem.2006.10.081]
[10]
Stephen, D.W.; Jamieson, D.J. Glutathione is an important antioxidant molecule in the yeast Saccharomyces cerevisiae. FEMS Microbiol. Lett., 1996, 141(2-3), 207-212.
[http://dx.doi.org/10.1111/j.1574-6968.1996.tb08386.x] [PMID: 8768524]
[11]
Martins, P.F.; Carvalho, G.; Gratão, P.L.; Dourado, M.N.; Pileggi, M.; Araújo, W.L.; Azevedo, R.A. Effects of the herbicides acetochlor and metolachlor on antioxidant enzymes in soil bacteria. Process Biochem., 2011, 46, 1186-1195.
[http://dx.doi.org/10.1016/j.procbio.2011.02.014]
[12]
Stuerenburg, H.J.; Kunze, K. Concentrations of free carnosine (a putative membrane-protective antioxidant) in human muscle biopsies and rat muscles. Arch. Gerontol. Geriatr., 1999, 29(2), 107-113.
[http://dx.doi.org/10.1016/S0167-4943(99)00020-5] [PMID: 15374064]
[13]
Bonfanti, L.; Peretto, P.; De Marchis, S.; Fasolo, A. Carnosine-related dipeptides in the mammalian brain. Prog. Neurobiol., 1999, 59(4), 333-353.
[http://dx.doi.org/10.1016/S0301-0082(99)00010-6] [PMID: 10501633]
[14]
Samaranayaka, A.G.; Li-Chan, E.C. Food-derived peptidic antioxidants: A review of their production, assessment, and potential applications. J. Funct. Foods, 2011, 3, 229-254.
[http://dx.doi.org/10.1016/j.jff.2011.05.006]
[15]
Doucet, O.; Pujos, M.; Robert, C.; Bernini, D. Cosmetic composition for use in increasing the collagen synthesis in skin cells. E.P. Patent 2514403A1, Nov,. 2013.
[16]
Zhang, X.; Zeng, Q. Hexapeptide and its application in preparation of pharmaceutical and cosmetic. C.N. Patent 105131086A, Oct,. 2018.
[17]
Fan, J.; He, J.; Zhuang, Y.; Sun, L. Purification and identification of antioxidant peptides from enzymatic hydrolysates of Tilapia (Oreochromis niloticus) frame protein. Molecules, 2012, 17(11), 12836-12850.
[http://dx.doi.org/10.3390/molecules171112836] [PMID: 23117426]
[18]
Nikoo, M.; Benjakul, S.; Ehsani, A.; Li, J.; Wu, F.; Yang, N.; Xu, B.; Jin, Z.; Xu, X. Antioxidant and cryoprotective effects of a tetrapeptide isolated from Amur sturgeon skin gelatin. J. Funct. Foods, 2014, 7, 609-620.
[http://dx.doi.org/10.1016/j.jff.2013.12.024]
[19]
Ruban, G.Q. Acipenser schrenckii; The IUCN Red List of Threatened Species, 2010.
[20]
Zou, T-B.; He, T-P.; Li, H-B.; Tang, H-W.; Xia, E-Q. The structure-activity relationship of the antioxidant peptides from natural proteins. Molecules, 2016, 21(1), 72.
[http://dx.doi.org/10.3390/molecules21010072] [PMID: 26771594]
[21]
Barlos, K.; Chatzi, O.; Gatos, D.; Stavropoulos, G. 2-Chlorotrityl chloride resin. Studies on anchoring of Fmoc-amino acids and peptide cleavage. Int. J. Pept. Protein Res., 1991, 37(6), 513-520.
[PMID: 1917309]
[22]
Chan, W.C.; White, P.D. Fmoc solid phase peptide synthesis; Oxford University Press: Oxford, 2000.
[23]
Cai, L.; Wu, X.; Zhang, Y.; Li, X.; Ma, S.; Li, J. Purification and characterization of three antioxidant peptides from protein hydrolysate of grass carp (Ctenopharyngodon idella) skin. J. Funct. Foods, 2015, 16, 234-242.
[http://dx.doi.org/10.1016/j.jff.2015.04.042]


Rights & PermissionsPrintExport Cite as

Article Details

VOLUME: 15
ISSUE: 6
Year: 2019
Page: [680 - 685]
Pages: 6
DOI: 10.2174/1573407214666180417152417

Article Metrics

PDF: 24
HTML: 2
EPUB: 1
PRC: 1