Characterization of the Organic Component of Low-Molecular-Weight Chromium-Binding Substance and Its Binding of Chromium

Chen, Yuan; Watson, Heather M.; Gao, Junjie; Sinha, Sarmistha; Cassady, Carolyn J.; Vincent, John B.

doi:10.3945/jn.111.139147

Cited by 45 publications

(24 citation statements)

References 35 publications

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“…EEEEGDD is a fragment of low-molecular weight chromium-binding substance (LMWCr, also known as chromodulin), a biological peptide found in humans and animals that is involved in metabolism [63–65] and may have utility in diabetes treatment [66]. We have recently sequenced a biological form of this peptide, pEEEEGDD [67]. This was a challenge because the high acidity of the peptide resulted in only deprotonation by ESI and MALDI.…”

Section: Resultsmentioning

confidence: 99%

The Use of Chromium(III) to Supercharge Peptides by Protonation at Low Basicity Sites

Feng

Commodore

Cassady

2014

J. Am. Soc. Mass Spectrom.

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The addition of chromium(III) nitrate to solutions of peptides with seven or more residues greatly increases the formation of doubly protonated peptides, [M+2H]2+, by electrospray ionization. The test compound heptaalanine has only one highly basic site (the N-terminal amino group) and undergoes almost exclusive single protonation using standard solvents. When Cr(III) is added to the solution, abundant [M+2H]2+ forms, which involves protonation of the peptide backbone or the C-terminus. Salts of Al(III), Mn(II), Fe(III), Fe(II), Cu(II), Zn (II), Rh(III), La(III), Ce(IV), and Eu(III) were also studied. While several metal ions slightly enhance protonation, Cr(III) has by far the greatest ability to generate [M+2H]2+. Cr(III) does not supercharge peptide methyl esters, which suggests that the mechanism involves interaction of Cr(III) with a carboxylic acid group. Other factors may include the high acidity of hexaaquochromium(III) and the resistance of Cr(III) to reduction. Nitrate salts enhance protonation more than chloride salts and a molar ratio of 10:1 Cr(III):peptide produces the most intense [M+2H]2+. Cr(III) also supercharges numerous other small peptides, including highly acidic species. For basic peptides, Cr(III) increases the charge state (2+ versus 1+) and causes the number of peptide molecules being protonated to double or triple. Chromium(III) does not supercharge the proteins cytochrome c and myoglobin. The ability of Cr(III) to enhance [M+2H]2+ intensity may prove useful in tandem mass spectrometry because of the resulting overall increase in signal-to-noise ratio, the fact that [M+2H]2+ generally dissociate more readily than [M+H]+, and the ability to produce [M+2H]2+ precursors for electron-based dissociation techniques.

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Section: Resultsmentioning

confidence: 99%

The Use of Chromium(III) to Supercharge Peptides by Protonation at Low Basicity Sites

Feng

Commodore

Cassady

2014

J. Am. Soc. Mass Spectrom.

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“…We have previously found that trivalent chromium, Cr(III), readily cationizes acidic and neutral peptides [58, 68, 69] and that during CID these Cr(III)-peptide ions undergo extensive sequence-informative fragmentation [68]. Also, Cr(III) readily binds to acidic peptides in solution [10, 70, 71]. However, Cr(III) proved to be a poor choice for sequencing fibrinopeptide B by ETD (see Supplementary Figure S9).…”

Section: Discussionmentioning

confidence: 99%

The Effects of Trivalent Lanthanide Cationization on the Electron Transfer Dissociation of Acidic Fibrinopeptide B and its Analogs

Commodore

Cassady

2016

J. Am. Soc. Mass Spectrom.

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Electrospray ionization (ESI) on mixtures of acidic fibrinopeptide B and two peptide analogs with trivalent lanthanide salts generates [M + Met + H]4+, [M + Met]3+, and [M + Met − H]2+, where M = peptide and Met = metal (except radioactive promethium). These ions undergo extensive and highly efficient electron transfer dissociation (ETD) to form metallated and non-metallated c- and z-ions. All metal adducted product ions contain at least two acidic sites, which suggests attachment of the lanthanide cation at the side chains of one or more acidic residues. The three peptides undergo similar fragmentation. ETD on [M + Met + H]4+ leads to cleavage at every residue; the presence of both a metal ion and an extra proton is very effective in promoting sequence-informative fragmentation. Backbone dissociation of [M + Met]3+ is also extensive, although cleavage does not always occur between adjacent glutamic acid residues. For [M + Met − H]2+, a more limited range of product ions form. All lanthanide metal peptide complexes display similar fragmentation except for europium (Eu). ETD on [M + Eu − H]2+ and [M + Eu]3+ yields a limited amount of peptide backbone cleavage; however, [M + Eu + H]4+ dissociates extensively with cleavage at every residue. With the exception of the results for Eu(III), metallated-peptide ion formation by ESI, ETD fragmentation efficiencies, and product ion formation are unaffected by the identity of the lanthanide cation. Adduction with trivalent lanthanide metal ions is a promising tool for sequence analysis of acidic peptides by ETD.

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“…This led to a number of studies designed to isolate and characterize endogenous LMWCr and synthetic molecular mimics of LMWCr . A recently published report claims to have characterized the structure of the apoLMWCr which may pave way for future studies in understanding the role of the polypeptide in the management of diabetes [36]. …”

Section: Chromium and Insulin Signalingmentioning

confidence: 99%

Molecular mechanisms of chromium in alleviating insulin resistance

Hua

Clark

Ren

et al. 2012

The Journal of Nutritional Biochemistry

190

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Type 2 diabetes is often associated with obesity, dyslipidemia, and cardiovascular anomalies and is a major health problem approaching global epidemic proportions. Insulin resistance, a prediabetic condition, precedes the onset of frank type 2 diabetes and offers potential avenues for early intervention to treat the disease. Although lifestyle modifications and exercise can reduce the incidence of diabetes, compliance has proved to be difficult, warranting pharmacological interventions. However, most of the currently available drugs that improve insulin sensitivity have adverse effects. Therefore, attractive strategies to alleviate insulin resistance include dietary supplements. One such supplement is chromium, which has been shown reduce insulin resistance in some, but not all, studies. Furthermore, the molecular mechanisms of chromium in alleviating insulin resistance remain elusive. This review examines emerging reports on the effect of chromium, as well as molecular and cellular mechanisms by which chromium may provide beneficial effects in alleviating insulin resistance.

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Characterization of the Organic Component of Low-Molecular-Weight Chromium-Binding Substance and Its Binding of Chromium

Cited by 45 publications

References 35 publications

The Use of Chromium(III) to Supercharge Peptides by Protonation at Low Basicity Sites

The Use of Chromium(III) to Supercharge Peptides by Protonation at Low Basicity Sites

The Effects of Trivalent Lanthanide Cationization on the Electron Transfer Dissociation of Acidic Fibrinopeptide B and its Analogs

Molecular mechanisms of chromium in alleviating insulin resistance

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