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The structure and function of peptides are affected by the changes of environmental factors, including temperature, pH value and ionic strength. Sugar groups can form covalent bonds with amino acid side chain groups of peptides to undergo structural modification, and then the glycosylation modification can effectively improve the stability and biological activity of peptide molecules. In this review, the preparation methods and structural characterization strategies of glycosylated peptides were summarized, and the recent research progress on their physiological activities were highlighted. The challenges and future research directions of glycosylated peptides were also discussed.

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[1] 陈月华, 程云辉, 许宙, 等. 食源性生物活性肽免疫调节功能研究进展[J]. 食品与机械, 2016, 32(5): 209-213. CHEN Y H, CHENG Y H, XU Z, et al. Research progress in immunomodulatory function of food-derived bioactive peptides[J]. Food & Machinery, 2016, 32(5): 209-213.
[2] SHI J, ZHAO X H. In vitro immuno-modulatory ability of tryptic caseinate hydrolysate affected by prior caseinate glycation using the Maillard reaction or transglutaminase[J]. Food and Agricultural Immunology, 2017, 28(6): 1 029-1 045.
[3] LI M, MCCLEMENTS D J, LIU X, et al. Design principles of oil-in-water emulsions with functionalized interfaces: Mixed, multilayer, and covalent complex structures[J]. Comprehensive Reviews in Food Science and Food Safety, 2020, 19(6): 3 159-3 190.
[4] ZHANG X X, LI X D, LIU L, et al. Covalent conjugation of whey protein isolate hydrolysates and galactose through Maillard reaction to improve the functional properties and antioxidant activity[J]. International Dairy Journal, 2020, 102: 104584.
[5] HE W Y, TIAN L, FANG F, et al. Heat-induced glycosylation with dextran to enhance solubility and interfacial properties of enzymatically hydrolyzed zein[J]. Journal of Food Engineering, 2022, 321: 110946.
[6] YU M, HE S D, TANG M M, et al. Antioxidant activity and sensory characteristics of Maillard reaction products derived from different peptide fractions of soybean meal hydrolysate[J]. Food Chemistry, 2018, 243: 249-257.
[7] ZHAO M G, MA A M, HE H, et al. Desalted duck egg white peptides-chitosan oligosaccharide copolymers as calcium delivery systems: Preparation, characterization and calcium release evaluation in vitro and vivo[J]. Food Research International, 2020, 131: 108974.
[8] ZHU B, HE H, GUO D, et al. Two novel calcium delivery systems fabricated by casein phosphopeptides and chitosan oligosaccharides: Preparation, characterization, and bioactive studies[J]. Food Hydrocolloids, 2020, 102: 105567.
[9] WANG C H, SHI S S, CHEN Q, et al. Antitumor and immunomodulatory activities of ganoderma lucidum polysaccharides in glioma-bearing rats[J]. Integrative Cancer Therapies, 2018, 17(3): 674-683.
[10] CONG H H, WU Q M, ZHANG Z R, et al. Improvement of functional characteristics of hypophthalmichthys molitrix protein by modification with chitosan oligosaccharide[J]. Frontiers in Nutrition, 2023, 10: 1140191.
[11] HAN Y, WANG L X, JIANG W P, et al. An enhanced stability nanoparticle preparation by corn protein hydrolysate-carboxymethyl chitosan Maillard conjugates loaded with rutin[J]. Journal of Food Science, 2019, 84(7): 1 829-1 835.
[12] CHEN K, YANG Q, HONG H, et al. Physicochemical and functional properties of Maillard reaction products derived from cod (Gadus morhua L.) skin collagen peptides and xylose[J]. Food Chemistry, 2020, 333: 127489.
[13] KCHAOU H, BENBETTAIEB N, JRIDI M, et al. Influence of Maillard reaction and temperature on functional, structure and bioactive properties of fish gelatin films[J]. Food Hydrocolloids, 2019, 97: 105196.
[14] DALEFIELD R R, MUELLER U. Gastric mucosal irritation following oral exposure to sodium metabisulphite: A reproducible effect?[J]. Regulatory Toxicology and Pharmacology, 2016, 80: 277-282.
[15] HOU C, WU S, XIA Y, et al. A novel emulsifier prepared from Acacia seyal polysaccharide through Maillard reaction with casein peptides[J]. Food Hydrocolloids, 2017, 69: 236-241.
[16] YANG S Y, LEE S, PYO M C, et al. Improved physicochemical properties and hepatic protection of Maillard reaction products derived from fish protein hydrolysates and ribose[J]. Food Chemistry, 2017, 221: 1 979-1 988.
[17] PIRESTANI S, NASIRPOUR A, KERAMAT J, et al. Preparation of chemically modified canola protein isolate with gum Arabic by means of Maillard reaction under wet-heating conditions[J]. Carbohydrate Polymers, 2017, 155: 201-207.
[18] CHEN X, ZOU Y, WANG D, et al. Effects of ultrasound pretreatment on the extent of Maillard reaction and the structure, taste and volatile compounds of chicken liver protein[J]. Food Chemistry, 2020, 331: 127369.
[19] XU W, ZHAO X H. Structure and property changes of the soy protein isolate glycated with maltose in an ionic liquid through the Maillard reaction[J]. Food & Function, 2019, 10(4): 1 948-1 957.
[20] RUIZ G A, XI B, MINOR M, et al. High-Pressure-High-Temperature processing reduces Maillard reaction and viscosity in whey protein-sugar solutions[J]. Journal of Agricultural and Food Chemistry, 2016, 64(38): 7 208-7 215.
[21] CHEN X, JIANG D, XU P, et al. Structural and antimicrobial properties of Maillard reaction products in chicken liver protein hydrolysate after sonication[J]. Food Chemistry, 2021, 343: 128417.
[22] LIU S, CAO W, WANG Y, et al. Characteristics and mechanisms of nitrogen transformation during chicken manure gasification in supercritical water[J]. Waste Management, 2022, 153: 240-248.
[23] MA X J, GAO J Y, TONG P, et al. Tracking the behavior of Maillard browning in lysine/arginine-sugar model systems under high hydrostatic pressure[J]. Journal of the Science of Food and Agriculture, 2017, 97(15): 5 168-5 175.
[24] DUARTE L, MATTE C R, BIZARRO C V, et al. Review transglutaminases: Part II-industrial applications in food, biotechnology, textiles and leather products[J]. World Journal of Microbiology & Biotechnology, 2019, 36(1): 11.
[25] DUARTE L, MATTE C R, BIZARRO C V, et al. Transglutaminases: Part I-origins, sources, and biotechnological characteristics[J]. World Journal of Microbiology & Biotechnology, 2020, 36(1): 15.
[26] SHEN M L, CIOU J Y, HSIEH L S, et al. Recombinant Streptomyces netropsis transglutaminase expressed in Komagataella phaffii (Pichia pastoris) and applied in plant-based chicken nugget[J]. World Journal of Microbiology & Biotechnology, 2023, 39(8): 200.
[27] PARROTTA L, TANWAR U K, ALOISI I, et al. Plant transglutaminases: New insights in biochemistry, genetics, and physiology[J]. Cells, 2022, 11(9): 1 529.
[28] KIELISZEK M, MISIEWICZ A. Microbial transglutaminase and its application in the food industry: A review[J]. Folia Microbiologica, 2014, 59(3): 241-250.
[29] CHEN H R, WU D, MA W C, et al. Strong fish gelatin hydrogels double crosslinked by transglutaminase and carrageenan[J]. Food Chemistry, 2022, 376: 131873.
[30] LIU J P, ZHANG Y Q, HE S Z, et al. Microbial transglutaminase-induced cross-linking of sodium caseinate as the coating stabilizer of zein nanoparticles[J]. LWT-Food Science and Technology, 2021, 138: 110624.
[31] FUCHSBAUER H L. Approaching transglutaminase from streptomyces bacteria over three decades[J]. Febs Journal, 2022, 289(16): 4 680-4 703.
[32] YANG R, ZUO P, ZHANG M, et al. Transglutaminase induced oligochitosan glycosylation of ferritin as a novel nanocarrier for food bioactive molecules[J]. Food Hydrocolloids, 2019, 94: 500-509.
[33] JIANG Z, WANG L, WU W, et al. Biologicalactivities and physicochemical properties of Maillard reaction products in sugar-bovine casein peptide model systems[J]. Food Chemistry, 2013, 141(4): 3 837-3 845.
[34] BI B W, YANG H, FANG Y P, et al. Characterization and emulsifying properties of beta-lactoglobulin-gum Acacia Seyal conjugates prepared via the Maillard reaction[J]. Food Chemistry, 2017, 214: 614-621.
[35] CHEN X, FANG F, WANG S. Physicochemical properties and hepatoprotective effects of glycated Snapper fish scale peptides conjugated withxylose via maillard reaction[J]. Food and Chemical Toxicology, 2020, 137: 111115.
[36] ZHANG C, WANG Z G, LI Y, et al. The preparation and physiochemical characterization of rapeseed protein hydrolysate-chitosan composite films[J]. Food Chemistry, 2019, 272: 694-701.
[37] DONG S Y, PAN Y A, ZENG M Y, et al. Characteristics and antioxidant activity of hydrolyzed beta-lactoglobulin-glucose Maillard reaction products[J]. Food Research International, 2013, 51(2): 992.
[38] LI Y, ZHONG F, JI W, et al. Functional properties of Maillard reaction products of rice protein hydrolysates with mono-, oligo- and polysaccharides[J]. Food Hydrocolloids, 2013, 30(1): 53-60.
[39] GAZI I, FRANC V, TAMARA S, et al. Identifying glycation hot-spots in bovine milk proteins duringproduction and storage of skim milk powder[J]. International Dairy Journal, 2022, 129: 105340.
[40] SONG R, SHI Q, YANG P, et al. Identification of antibacterial peptides from Maillard reaction products of half-fin anchovy hydrolysates/glucose via LC-ESI-QTOF-MS analysis[J]. Journal of Functional Foods, 2017, 36: 387-395.
[41] BAI Y, LIANG Y, LI G, et al. Metal-ion-assisted structural and anomeric analysis of Amadori compounds by electrospray ionization mass spectrometry[J]. Rapid Communications in Mass Spectrometry, 2021, 35(1): e8960.
[42] ESHGHI S T, YANG W, HU Y, et al. Classification of tandem mass spectra for identification of N- and O-linked glycopeptides[J]. Scientific Reports, 2016, 6: 37189.
[43] LIU X L, WANG J T, LIU Y, et al. Conjugation of the glutelin hydrolysates-glucosamine by transglutaminase and functional properties and antioxidant activity of the products[J]. Food Chemistry, 2022, 380: 132210.
[44] QIAO G H, WENXIM D, ZHIGANG X, et al. Antioxidant and anti-inflammatory capacities of pepper tissue[J]. Italian Journal of Food Science, 2020, 32(2): 265-274.
[45] SHARIPOV A, TURSUNOV K, FAZLIEV S, et al. Hypoglycemic and anti-inflammatory effects of triterpene glycoside fractions from aeculus hippocastanum seeds[J]. Molecules, 2021, 26(13): 3 784.
[46] LIU L, LI S, ZHENG J, et al. Safety considerations on food protein-derived bioactive peptides[J]. Trends in Food Science & Technology, 2020, 96: 199-207.
[47] CHEN J Y, SUN Y J, HUANG S, et al. Grub polypeptide extracts protect against oxidative stress through the NRF2-ARE signaling pathway[J]. Animal Cells and Systems, 2021, 25(6): 405-415.
[48] LIU X L, WANG J T, LIU Y, et al. Conjugation of the glutelin hydrolysates-glucosamine by transglutaminase and functional properties and antioxidant activity of the products[J]. Food Chemistry, 2022, 380: 132210.
[49] NGOH Y Y, GAN C Y. Enzyme-assisted extraction and identification of antioxidative and alpha-amylase inhibitory peptides from Pinto beans (Phaseolus vulgaris cv. Pinto)[J]. Food Chemistry, 2016, 190: 331-337.
[50] CUI H, HAYAT K, ZHANG X. Antioxidant activity in vitro of N-(1-deoxy-alpha-d-xylulos-1-yl)-Phenylalanine: Comparison among Maillard reaction intermediate, end-products and xylose-phenylalanine[J]. Journal of Food Science, 2019, 84(5): 1 060-1 067.
[51] NOOSHKAM M, VARIDI M, BASHASH M. The Maillard reaction products as food-born antioxidant and antibrowning agents in model and real food systems[J]. Food Chemistry, 2019, 275: 644-660.
[52] JIANG W, LIU Y, YANG X Q, et al. Antioxidant and antibacterial activities of modified crab shell bioactive peptides by Maillard reaction[J]. International Journal of Food Properties, 2018, 21(1): 2 730-2 743.
[53] LIU M, MIN L, ZHU C, et al. Preparation, characterization and antioxidant activity of silk peptides grafted carboxymethyl chitosan[J]. International Journal of Biological Macromolecules, 2017, 104: 732-738.
[54] WANG Q H, KUANG H X, SU Y, et al. Naturally derived anti-inflammatory compounds from Chinese medicinal plants[J]. Journal of Ethnopharmacology, 2013, 146(1): 9-39.
[55] CHENG X, GAO D, CHEN B, et al. Endotoxin-Binding peptides derived from casein glycomacropeptide inhibit lipopolysaccharide-stimulated inflammatory responses via blockade of NF-kappa B activation in macrophages[J]. Nutrients, 2015, 7(5): 3 119-3 137.
[56] ROLDAN N R, JIMENEZ M, CERVANTES-GARCIA D, et al. Glycomacropeptide administration attenuates airway inflammation and remodeling associated to allergic asthma in rat[J]. Inflammation Research, 2016, 65(4): 273-283.
[57] ORTEGA-GONZALEZ M, CAPITAN-CANADAS F, REQUENA P, et al. Validation of bovine glycomacropeptide as an intestinal anti-inflammatory nutraceutical in the lymphocyte-transfer model of colitis[J]. British Journal of Nutrition, 2014, 111(7): 1 202-1 212.
[58] CHENG X, GAO D X, CHEN B, et al. Endotoxin-binding peptides derived from casein glycomacropeptide inhibit lipopolysaccharide-stimulated inflammatory responses via blockade of NF-kappa B activation in macrophages[J]. Nutrients, 2015, 7(5): 3 119-3 137.
[59] LI T G, GAO D X, DU M, et al. Casein glycomacropeptide hydrolysates inhibit PGE2 production and COX2 expression in LPS-stimulated RAW 264.7 macrophage cells via Akt mediated NF-kappa B and MAPK pathways[J]. Food & Function, 2018, 9(4): 2 524-2 532.
[60] REYES-PAVON D, CERVANTES-GARCIA D, BERMUDEZ-HUMARAN L G, et al. Protective effect of glycomacropeptide on food allergy with gastrointestinal manifestations in a rat model through down-regulation of type 2 immune response[J]. Nutrients, 2020, 12(10): 2 942.
[61] KARNJANAPRATUM S, O'CALLAGHAN Y C, BENJAKUL S, et al. In vitro cellular bioactivities of Maillard reaction products from sugar-gelatin hydrolysate of unicorn leatherjacket skin system[J]. Journal of Functional Foods, 2016, 23: 87-94.
[62] ORLIAGUET L, EJLALMANESH T, ALZAID F. Metabolic and molecular mechanisms of macrophage polarisation and adipose tissue insulin resistance[J]. International Journal of Molecular Sciences, 2020, 21(16): 5 731.
[63] BRUNTON S. GLP-1 receptor agonists vs. DPP-4 inhibitors for type 2 diabetes: Is one approach more successful or preferable than the other?[J]. International Journal of Clinical Practice, 2014, 68(5): 557-567.
[64] WANG X, SON M, MERAM C, et al. Mechanism and potential of egg consumption and egg bioactive components on type-2 diabetes[J]. Nutrients, 2019, 11(2): 357.
[65] SONG J J, GAO J, DU M, et al. Casein glycomacropeptide hydrolysates ameliorate hepatic insulin resistance of C57BL/6J mice challenged with high-fat diet[J]. Journal of Functional Foods, 2018, 45: 190-198.
[66] YUAN Q C, ZHAN B Y, CHANG R, et al. Antidiabetic effect of casein glycomacropeptide hydrolysates on high-fat diet and STZ-induced diabetic mice via regulating insulin signaling in skeletal muscle and modulating gut microbiota[J]. Nutrients, 2020, 12(1): 220.
[67] SONG J J, WANG Q, DU M, et al. Casein glycomacropeptide-derived peptide IPPKKNQDKTE ameliorates high glucose-induced insulin resistance in HepG2 cells via activation of AMPK signaling[J]. Molecular Nutrition & Food Research, 2017, 61(2): 1600301.
[68] SANKARGANESH M, RAJESH J, KUMAR G G V, et al. Synthesis, spectral characterization, theoretical, antimicrobial, DNA interaction and in vitro anticancer studies of Cu(II) and Zn(II) complexes with pyrimidine-morpholine based Schiff base ligand[J]. Journal of Saudi Chemical Societ, 2018, 22(4): 416-426.
[69] CHUDINOVA Y V, SHAGDAROVA B T, IL'INA A V, et al. Antibacterial effect of peptide conjugates with a quaternized chitosan derivative and its estimation by the method of atomic force microscopy[J]. Applied Biochemistry and Microbiology, 2016, 52(5): 496-501.
[70] RONG Y, LU Z, ZHANG H, et al. Effects of casein glycomacropeptide supplementation on growth performance, intestinal morphology, intestinal barrier permeability and inflammatory responses in Escherichia coli K88 challenged piglets[J]. Animal Nutrition (Zhongguo Xu Mu Shou Yi Xue Hui), 2015, 1(2): 54-59.
[71] JIANG W, LIU Y, YANG X, et al. Antioxidant and antibacterial activities of modified crab shell bioactive peptides by Maillard reaction[J]. International Journal of Food Properties, 2018, 21(1): 2 730-2 743.
[72] BATOOL S, CHOKKAKULA S, SONG M S. Influenza treatment: Limitations of antiviral therapy and advantages of drug combination therapy[J]. Microorganisms, 2023, 11(1): 183.
[73] YAN J, LI J H, HU Z F, et al. Enzymatic synthesis of sialyl lactosamine grafted chitooligosaccharides[J]. Chinese Journal of Chemistry, 2023, 41(11): 1 299-1 304.
[74] SAUVE M F, SPAHIS S, DELVIN E, et al. Glycomacropeptide: A bioactive milk derivative to alleviate metabolic syndrome outcomes[J]. Antioxidants & Redox Signaling, 2021, 34(3): 201-222.
[75] TSUJI S, ASO Y, OHARA H, et al. Aqueous synthesis of sialylglycopeptide-grafted glycopolymers with high affinity for the lectin and the influenza virus hemagglutinin[J]. Journal of Polymer Science, 2020, 58(4): 548-556.
[76] STADTMUELLER M N, BHATIA S, KIRAN P, et al. Evaluation of multivalent sialylated polyglycerols for resistance induction in and broad antiviral activity against influenza a viruses[J]. Journal of Medicinal Chemistry, 2021, 64(17): 12 774-12 789.



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