In systems of biological origin, reducing sugars and other reactive carbonyl species like glyoxal are ubiquitous. Some of these may react non-enzymatically with the amino moieties of proteins, i.e., with the side chains of the amino acid lysine. These modifications are favored by prolonged reaction times and elevated temperatures. The reaction products of amines with sugars are named Maillard Reaction Products (MRPs), after Louis-Camille Maillard, a French scientist who has described the reaction between amines and sugars forming brownish products in 1912. They are also known as advanced glycation end products (AGEs).

Maillard products also may be formed during food-processing and can be quantified as indicator for thermal processing. There, MRPs are responsible for the brown color of, e.g., roasted meat, coffee and gingerbread, and are appreciated for their delicious and characteristic flavors.

In vivo, the glycosylation of proteins may impair their function and is associated with ageing, diabetes, cardiovascular and renal disease. HbA_1c (glycated hemoglobin) is an easily accessible blood borne biomarker, which is widely used to assess long-term glucose homeostasis and control, esp. in patients with diabetes.

The reactive metabolites glyoxal and methylglyoxal may crosslink proteins by forming imidazolium and methylimidazolium bridges between lysines. Maltosine and pyridosine may be found in beer and honey, dihydroxyacetone (DHA) is a key ingredient of sunless tanning products and exerts its coloring effect by converting skin proteins into AGE products.

Fmoc and Benzyl protected L-Maltosine (FAA9415, left), Fmoc2-GOLD (FAA9405) and Fmoc2-MOLD (FAA9410, with a methyl group at the imidazolium bridge, highlighted in red).

To support your studies of the effect of glycated amino acids in peptides and proteins, we have added three lysine derivatives as protected building blocks for Fmoc-peptide synthesis to our portfolio: Fmoc-2-GOLD (FAA9405), Fmoc2-MOLD (FAA9410) - both are imidazolium derivatives, representing crosslinked lysines - and Fmoc-L-Maltosine(Bzl)-OH (FAA9415), as well as the three lysine derivatives pyridosine (HAA9590), maltosine (HAA9560) and Lys-dihydroxyacetone (Lys-DHA) (HAA9600) for analytical purposes or further derivatization by yourself.

Structures of the L-lysine derivatives Lys-DHA (HAA9600), Pyridosine (HAA9590) and Maltosine (HAA9560). The latter two differ in the position of a methyl group at the oxopyridine system.

→ Discover our complete Maillard-Portfolio in our dedicated flyer!

→You are looking for a special Maillard reaction product not listed in our catalogue? Please inquire for a custom synthesis!

References:

Action of amino acids on sugars. Formation of Melanoidins in a Methodical Way; L. C. Maillard; Compt. Rend. 1912; 154: 66.

Food Processing and Maillard Reaction Products: Effect on Human Health and Nutrition; N. Tamanna, N. Mahmood; Int. J. Food. Sci. 2015; 526762. https://doi.org/10.1155/2015/526762

Health effects of dietary Maillard reaction products: the results of ICARE and other studies; F. J. Tessier, I. Birlouez-Aragon; Amino Acids 2010; 42: 1119 - 1131. https://doi.org/10.1007/s00726-010-0776-z

Role of the Maillard reaction in aging of tissue proteins. Advanced glycation end product-dependent increase in imidazolium cross-links in human lens proteins; E. B. Frye, T. P. Degenhardt, S. R. Thorpe, J. W. Baynes; J. Biol. Chem. 1998; 273(80): 18714-18719. https://doi.org/10.1074/jbc.273.30.18714

Imidazolium crosslinks derived from reaction of lysine with glyoxal and methylglyoxal are increased in serum proteins of uremic patients: evidence for increased oxidative stress in uremia; H. Odani, T. Shinzato, J. Usami, Y. Matsumoto, E. Brinkmann Frye, J. W. Baynes, K. Maeda; FEBS Lett. 1998; 427(3): 381-385. https://doi.org/10.1016/s0014-5793(98)00416-5

Protein crosslinking by the Maillard reaction: dicarbonyl-derived imidazolium crosslinks in aging and diabetes; P. Chellan, R. H. Nagaraj; Arch. Biochem. Biophys. 1999; 368(1): 98-104. https://doi.org/10.1006/abbi.1999.1291

Protein cross-linking by the Maillard reaction. Isolation, characterization, and in vivo detection of a lysine-lysine cross-link derived from methylglyoxal; R. H. Nagaraj, I. N. Shipanova, F. M. Faust; J. Biol. Chem. 1996; 271(32): 19338-19345. https://doi.org/10.1074/jbc.271.32.19338

Therapeutic potential of breakers of advanced glycation end product-protein crosslinks; S. Vasan, P. Foiles, H. Founds; Arch. Biochem. Biophys. 2003; 419(1): 89-96.https://doi.org/10.1016/j.abb.2003.08.016

Random coil shifts of posttranslationally modified amino acids; A. C. Conibear, K. J. Rosengren, C. F. W. Becker, H. Kaehlig; J. Biomol. NMR 2019; 73: 587-599. https://doi.org/10.1007/s10858-019-00270-4

Control of Maillard Reactions in Foods: Strategies and Chemical Mechanisms; M. N. Lund, C. A. Ray; J. Agric. Food Chem. 2017; 65(23): 4537-4552. https://doi.org/10.1021/acs.jafc.7b00882

Site-specific cross-linking of collagen peptides by lysyl advanced glycation endproducts; M. Kamalov, P. W. R. Harris, G. J. S. Cooper, M. A. Brimble. Chem. Commun. 2014; 50: 4944-4946. https://doi.org/10.1039/C4CC02003K

Chemical Synthesis of Peptides Containing Site-Specific Advanced Glycation Endproducts; H. Kaur, M. Kamalov, M. A. Brimble; Accounts Chem. Res. 2016; 49(10): 2199-2208. https://doi.org/10.1021/acs.accounts.6b00366

Yeast Metabolites of Glycated Amino Acids in Beer; M. Hellwig, F. Beer, S. Witte, T. Henle; J. Agric Food Chem. 2018; 66(28): 7451-7460. https://doi.org/10.1021/acs.jafc.8b01329

Free and Protein-Bound Maillard Reaction Products in Beer: Method Development and a Survey of Different Beer Types; M. Hellwig, S. Witte, T. Henle; J. Agric. Food Chem. 2016; 28(64): 7234-7243. https://doi.org/10.1021/acs.jafc.6b02649

Elucidation of the non-volatile fingerprint in oven headspace vapor from bread roll baking by ultra-high resolution mass spectrometry; L. Weidner, Y. Yan, D. Hemmler, M. Rychlick, P. Schmitt-Kopplin. Food. Chem. 2022; 16: 131618. https://doi.org/10.1016/j.foodchem.2021.131618

Unique Pattern of Protein-Bound Maillard Reaction Products in Manuka (Leptospermum scoparium) Honey; M. Hellwig, J. Rückriemen, D. Sandner, T. Henle; J. J. Agric. Food Chem. 2017; 65(17): 3532-3540. https://doi.org/10.1021/acs.jafc.7b00797

Quantitative determination of collagen cross-links; N. C. Avery, T. J. Sims, A. J. Bailey. Methods Mol. Biol. 2009; 522: 103-121. https://doi.org/10.1007/978-1-59745-413-1_6

The sunless tanning agent dihydroxyacetone induces stress response gene expression and signaling in cultured human keratinocytes and reconstructed epidermis; J. Perer, J. Jandova, J. Fimbres, E. Q. Jennings, J. J. Galligan, A. Hua, G. T. Wondrak; Redox Biol. 2020; 36: 101594. https://doi.org/10.1016/j.redox.2020.101594

Comparison of Color Development Kinetics of Tanning Reactions of Dihydroxyacetone with Free and Protected Basic Amino Acids; Y. Sun, S. Lee, L. Lin; ACS Omega 2022; 7(43): 45510-45517. https://doi.org/10.1021/acsomega.2c06124