Helical peptide models for protein glycation: proximity effects in catalysis of the Amadori rearrangement

Venkatraman, Janani; Aggarwal, Kamna; Balaram, Padmanabhan

doi:10.1016/s1074-5521(01)00036-9

Cited by 70 publications

(51 citation statements)

References 74 publications

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“…This might be attributed to nearby residues or more generally the local environment, i.e. reagent accessibility and nearby functional groups affecting the pK a of the Lys residue or acting as local acid/base catalysts in glycation reactions (56,58,59). Furthermore, the differences were relatively moderate (3-6-fold compared with the other cohorts) and were detected only in one peptide per modification type, which suggests that the changes would not be detectable with an analytical approach relying on protein hydrolysis.…”

Section: Discussionmentioning

confidence: 99%

Plasma Proteins Modified by Advanced Glycation End Products (AGEs) Reveal Site-specific Susceptibilities to Glycemic Control in Patients with Type 2 Diabetes

Greifenhagen

Frolov

Blüher

et al. 2016

Journal of Biological Chemistry

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Protein glycation refers to the reversible reaction between aldoses (or ketoses) and amino groups yielding relatively stable Amadori (or Heyns) products. Consecutive oxidative cleavage reactions of these products or the reaction of amino groups with other reactive substances (e.g. ␣-dicarbonyls) yield advanced glycation end products (AGEs) that can alter the structures and functions of proteins. AGEs have been identified in all organisms, and their contents appear to rise with some diseases, such as diabetes and obesity. Here, we report a pilot study using highly sensitive and specific proteomics approach to identify and quantify AGE modification sites in plasma proteins by reversed phase HPLC mass spectrometry in tryptic plasma digests. In total, 19 AGE modification sites corresponding to 11 proteins were identified in patients with type 2 diabetes mellitus under poor glycemic control. The modification degrees of 15 modification sites did not differ among cohorts of normoglycemic lean or obese and type 2 diabetes mellitus patients under good and poor glycemic control. The contents of two amide-AGEs in human serum albumin and apolipoprotein A-II were significantly higher in patients with poor glycemic control, although the plasma levels of both proteins were similar among all plasma samples. These two modification sites might be useful to predict long term, AGE-related complications in diabetic patients, such as impaired vision, increased arterial stiffness, or decreased kidney function.The reaction between reducing sugars (i.e. aldoses or ketoses) and amines is termed glycation or nonenzymatic glycosylation (1). The initially formed aldimines or ketimines can rearrange forming relatively stable Amadori or Heyns products, respectively. Consecutive rearrangements and oxidations yield advanced glycation end products (AGEs) 3 (2-6), a structurally heterogeneous group of compounds including cross-linked proteins (1). Alternatively, ␣-dicarbonyls generated by Amadori degradation (7,8), saccharide autoxidation (9, 10), lipid peroxidation (11, 12), and enzymatic reactions (13-15) can modify the side chains of lysine and arginine residues (16 -18). Degradation of glucose-derived Amadori products, for example, yields 1-deoxyglucosone (7, 19) and its tautomers, which upon nucleophilic attack by a N ⑀ -amino group of a lysine residue undergo hydrolytic ␤-cleavage yielding amide-AGEs, such as N ⑀ -acetyl-, formyl-, and glycerinyl-lysine ( Fig. 1) (20). Generally, AGEs can alter the structure of proteins contributing to diabetic retinopathy (21, 22), increased arterial stiffness (23, 24), or impaired renal function (25) along with aging and diabetes. Furthermore, receptor binding-induced activation of proinflammatory signaling pathways is associated with the development and progression of atherosclerosis (26) and nephropathy (25).AGEs have been localized in biological tissues by immunohistochemistry (27-29) and quantified with ELISA using monoclonal antibodies recognizing methylglyoxal-derived hydroimidazolone (30), imidazol...

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Section: Discussionmentioning

confidence: 99%

Plasma Proteins Modified by Advanced Glycation End Products (AGEs) Reveal Site-specific Susceptibilities to Glycemic Control in Patients with Type 2 Diabetes

Greifenhagen

Frolov

Blüher

et al. 2016

Journal of Biological Chemistry

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“…7a), but produced lower product amounts that could not be traced back to a higher product diversity. Whereas spatially proximate histidine has been reported to act as an acid-base-catalyst in the Amadori rearrangement, strongly basic residues such as arginine have been reported to enhance Amadori formation by reducing the lysine's pK a (Venkatraman et al 2001). Principally, a catalyst enhancing Amadori rearrangement should exert the same effect on the reverse reaction, which explains the faster deglycation when histidine is positioned i + 4.…”

Section: Discussionmentioning

confidence: 99%

Oxidative degradation of N ε-fructosylamine-substituted peptides in heated aqueous systems

2015

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Glycation, or non-enzymatic glycosylation, is a common protein modification formed by reactions between reducing sugars (i.e. aldoses and ketoses) with protein amino groups. Resulting Amadori and Heyns compounds, respectively, can be oxidatively degraded yielding a structurally heterogeneous group of advanced glycation end-products. We have studied this process in aqueous conditions at 95 °C in terms of appearing products and their formation kinetics in the presence or absence of reactive oxygen species (ROS)-generating systems (iron(II) sulfate). RP-HPLC-ESI-MS revealed 20 products, 12 of which were confirmed after synthesis by identical retention times and fragmentation patterns. These products accumulated during the incubation period of 4 h (N(ε)-carboxymethyl-, N(ε)-formyl- and N(ε)-methyl lysine) or appeared intermediately (2-aminoadipic semialdehyde, N(ε)-ethanalyl lysine). Acidic and basic amino acid residues near the glycation site and elevated ROS levels in the reaction mixture had significant effects on both product formation and degradation kinetics.

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“…The presence of a carboxylic acid has been proposed to act as an internal catalyst for glycation, with the oxygen atom acting as a nucleophile to propagate the conversion of the Schiff base to the more stable Amadori product. 26,27 As seen in Figure 5B, K99 has 2 carboxylic acids, D105 on the heavy chain and E61 on the light chain, in proximity (at 2.5A and 2.6A…”

Section: Structural Analysis Reveals a Putative Glycation Hotspot Mecmentioning

confidence: 94%

A chemical and computational approach to comprehensive glycation characterization on antibodies

Saleem

Affholter

Deng

et al. 2015

mAbs

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, liquid chromatography coupled with tandem mass spectrometry; mAb, monoclonal antibody; MS 1 , a mass to charge ratio survey scan; MS 2 , tandem mass spectrometry -selected ions from MS 1 are fragmented and fragment ion mass measured; UPLC, ultrahigh performance liquid chromatography Non-enzymatic glycation is a challenging post-translational modification to characterize due to the structural heterogeneity it generates in proteins. Glycation has become increasingly recognized as an important product quality attribute to monitor, particularly for the biotechnology sector, which produces recombinant proteins under conditions that are amenable to protein glycation. The elucidation of sites of glycation can be problematic using conventional collision-induced dissociation (CID)-based mass spectrometry because of the predominance of neutral loss ions. A method to characterize glycation using an IgG1 monoclonal antibody (mAb) as a model is reported here. The sugars present on this mAb were derivatized using sodium borohydride chemistry to stabilize the linkage and identified using CID-based MS 2 mass spectrometry and spectral search engines. Quantification of specific glycation sites was then done using a targeted MS 1 based approach, which allowed the identification of a glycation hot spot in the heavy chain complementarity-determining region 3 of the mAb. This targeted approach provided a path forward to developing a structural understanding of the propensity of sites to become glycated on mAbs. Through structural analysis we propose a model in which the number and 3-dimensional distances of carboxylic acid amino acyl residues create a favorable environment for glycation to occur.

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Helical peptide models for protein glycation: proximity effects in catalysis of the Amadori rearrangement

Cited by 70 publications

References 74 publications

Plasma Proteins Modified by Advanced Glycation End Products (AGEs) Reveal Site-specific Susceptibilities to Glycemic Control in Patients with Type 2 Diabetes

Plasma Proteins Modified by Advanced Glycation End Products (AGEs) Reveal Site-specific Susceptibilities to Glycemic Control in Patients with Type 2 Diabetes

Oxidative degradation of N ε-fructosylamine-substituted peptides in heated aqueous systems

A chemical and computational approach to comprehensive glycation characterization on antibodies

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