Darstellung aliphatischer Amadori‐Produkte

Quantification of the extent of glycation of human serum albumin (HSA) and of haemoglobin provides a record of average mid- and long-term blood-sugar concentrations, respectively; this is very useful for the management of diabetes. The reaction of D-glucose with propylamine affords the corresponding Schiff base, N-propylamino-D-glucoside, in the cyclic form. This compound is not stable: upon standing or treatment with acid it is converted, by an Amadori rearrangement, into N-propylfructosamine. Both amino sugars occur predominantly in the beta-pyranose form. Phenylboronate forms highly stable boronate esters through binding of the cis 1,2-diol moiety in the furanose form of N-propylfructosamine. Between pH 5 and 10, an electrostatic interaction between the protonated amino group and the negatively charged boronate moiety affords an additional stabilisation of the ester. The Schiff base, however, has no observable interaction with phenylboronate. In aqueous solution the Schiff base is in equilibrium with propylamine and glucose. Upon addition of phenylboronate, this equilibrium shifts to the side of glucose due to the formation of highly stable phenylboronate esters of the beta-furanose form of this compound. After Amadori rearrangement, the sugar moieties in glycated human serum albumin have a similar structure, they occur as an equilibrium of the beta-pyranose (59%), alpha-furanose (19%) and beta-furanose (24%) anomers. The open form was not observed. The beta-furanose anomer is selectively recognised by phenylboronate.

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“…[27,28] No solvent was applied in this reaction. Schiff base 3 a is stable at À 20 8C for at least a year.…”

Section: Resultsmentioning

confidence: 99%

The Structure of the Sugar Residue in Glycated Human Serum Albumin and Its Molecular Recognition by Phenylboronate

Rohovec

Maschmeyer

Aime

et al. 2003

Chemistry A European J

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“…For reducing AGE-Hb, NaBH 4 was employed as described by Horiuchi et al (14). 1-Deoxy-1-propylamino-D-fructose, an Amadori compound, was synthesized by the method of Micheel and Hagemann (15). N ␣ -Tosyl-N ⑀ -carboxymethyllysine methyl ester (CM-TsLME) was synthesized from N ␣ -tosyl-lysine methyl ester by the method of Ahmed et al (16) with minor modifications.…”

Section: Preparation Of Age-proteins and Amadorimentioning

confidence: 99%

Advanced Glycation End Products-driven Angiogenesis in Vitro

Yamagishi

Yonekura

Yamamoto

et al. 1997

Journal of Biological Chemistry

260

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This study was undertaken to determine whether and how advanced glycation end products (AGE), senescent macroproteins accumulated in various tissues under hyperglycemic states, cause angiogenesis, the principal vascular derangement in diabetic microangiopathy. We first prepared AGE-bovine serum albumin (BSA) and anti-AGE antiserum using AGE-RNase A. Then AGE-BSA was administered to human skin microvascular endothelial cells in culture, and their growth was examined. The AGE-BSA, but not nonglycated BSA, was found to induce a statistically significant increase in the number of viable endothelial cells as well as their synthesis of DNA. The increase in DNA synthesis by AGE-BSA was abolished by anti-AGE antibodies. AGE-BSA also stimulated the tube formation of endothelial cells on Matrigel. We obtained the following evidence that it is vascular endothelial growth factor (VEGF) that mainly mediates the angiogenic activities of AGE. Glucose and other reducing sugars can react nonenzymatically with the amino groups of proteins to form reversible Schiff bases and, then, Amadori products. These early glycation products undergo further complex reactions such as rearrangement, dehydration, and condensation to become irreversibly crosslinked, heterogeneous fluorescent derivatives termed advanced glycation end products (AGE) 1 (1). The formation and accumulation of AGE in various tissues have been known to progress during normal aging and at an extremely accelerated rate in diabetes mellitus. This has been implicated in the development of diabetic micro-and macro-vascular complications (1), which may account for the disabilities and high mortality rate in patients with this disease (2).Microvessels are composed of only two types of cells, endothelial cells and pericytes, and have been known to show both functional and structural abnormalities during prolonged diabetic exposure, resulting in the deleterious effects on the organs that they supply (3-5). Using pericyte-endothelial cell co-culture systems, we have shown previously that pericytes can not only regulate the growth but also preserve the prostacyclin-producing ability and protect against lipid peroxide-induced injury of endothelial cells (6). This has provided a basis for understanding how diabetic retinopathy develops consequent to "pericyte loss," the earliest histopathological hallmark in diabetic retinopathy (5, 7).Recently, we have found that AGE exert a growth inhibitory effect and a cell type-specific immediate toxicity on pericytes through interactions with their receptor for AGE (RAGE), a cell surface receptor belonging to the immunoglobulin superfamily (8), and have proposed a novel mechanism for pericyte loss (9). The AGE-induced, RAGE-mediated decrease in pericyte number would then indirectly cause angiogenesis (6,9).In the present study, we investigated the effects of AGE on the growth and tube formation of human skin microvascular endothelial cells, the key steps of angiogenesis. We demonstrate that AGE exert angiogenic activities directly on microvasc...

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“…1-Deoxyfructosyl propylamine (Amadori product) and N-glucosyl propylamine (Schiff base adduct) were prepared according to the method of Micheel and Hagemann (28). Briefly, 28 g (0.16 mol) of anhydrous glucose were dissolved in 28 ml (0.34 mol) of propylamine at 70°C.…”

Section: Reagentsmentioning

confidence: 99%

Involvement of Hydrogen Peroxide in Collagen Cross-linking by High Glucose in Vitro and in Vivo

Elgawish

Glomb

Friedlander

et al. 1996

Journal of Biological Chemistry

183

101

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The Maillard reaction has been implicated in crosslinking and fluorescence formation of collagen exposed to high glucose in vitro. However, several pharmacologic agents, whose action seems unrelated to pathways of nonenzymatic glycation, have been demonstrated to prevent cross-linking in diabetes. To clarify this discrepancy, kinetic changes in glycation, glycoxidation (carboxymethyllysine, CML), and cross-linking (measured as tendon breaking time, TBT) were evaluated in rat tail tendons incubated in 5 and 30 mM glucose in vitro and in tendons implanted in vivo into diabetic rat peritoneal cavity. In vitro, rates were found to be both O 2 -and glucose-dependent. Tendon preglycation and presence of added 2 mM glycosylamine and Amadori compounds (Amadori product of glucose and propylamine) catalyzed these changes in a primarily O 2 -dependent manner. In the presence of Amadori compounds, kinetic changes were dramatically increased and were preventable by addition of catalase to the medium. Tendons implanted into diabetic rat peritoneum became more rapidly glycoxidized and cross-linked when implanted at day 30 from diabetes onset (high tissue glycation) compared to day 3 (low tissue glycation) in spite of similar glycation kinetics, suggesting a mechanistic dissociation between glycation, glycoxidation, and crosslinking in diabetes. Indeed, intraperitoneal injection of catalase and other antioxidants dramatically suppressed cross-linking, fluorescence formation, and, to some extent, glycoxidation, without affecting glycation. This study confirms the role of oxidative stress in protein cross-linking by the Maillard reaction in vitro and provides the first evidence for a role of H 2 O 2 in crosslinking in diabetes. Whereas Amadori products are a potent source of H 2 O 2 formation in vitro, their precise contribution to H 2 O 2 generation and the actual role of Maillard reaction products in collagen cross-linking in diabetes requires further investigation.Considerable efforts have been devoted in recent years toward understanding of the pathogenetic mechanisms leading to collagen insolubilization in diabetes and aging (1-3). The rationale for this research lies in the hope that understanding the biochemical basis of stochastic mechanisms of damage to collagen will help elucidate their role in diabetic complications and aging. One key proposition is that protein cross-links are generated in the advanced Maillard reaction (4, 5). According to the original concept proposed by Hodge (6), the central molecule responsible for the advanced Maillard reaction is the Amadori product which, upon dehydration and rearrangement, forms highly reactive deoxyosones Ϫ potent precursors of protein cross-links. This concept was challenged by Namiki (7) who found that sugar fragmentation can also occur at the stage of the glycosylamine, or Schiff base, i.e. prior to the Amadori rearrangement. Glyoxal is then formed which can serve as a protein cross-link (8 -10). More recently, Wolff et al. (11) obtained evidence from in vitro experimenta...

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Darstellung aliphatischer Amadori‐Produkte

Cited by 38 publications

References 5 publications

The Structure of the Sugar Residue in Glycated Human Serum Albumin and Its Molecular Recognition by Phenylboronate

The Structure of the Sugar Residue in Glycated Human Serum Albumin and Its Molecular Recognition by Phenylboronate

Advanced Glycation End Products-driven Angiogenesis in Vitro

Involvement of Hydrogen Peroxide in Collagen Cross-linking by High Glucose in Vitro and in Vivo

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