Reactions of a modified lysine with aldehydic and diketonic dicarbonyl compounds: an electrospray mass spectrometry structure/activity study

2006 ◽  
Vol 41 (2) ◽  
pp. 216-228 ◽  
Author(s):  
Marco A. Saraiva ◽  
Carlos M. Borges ◽  
M. Helena Florêncio
2020 ◽  
Vol 64 (1) ◽  
pp. 97-110
Author(s):  
Christian Sibbersen ◽  
Mogens Johannsen

Abstract In living systems, nucleophilic amino acid residues are prone to non-enzymatic post-translational modification by electrophiles. α-Dicarbonyl compounds are a special type of electrophiles that can react irreversibly with lysine, arginine, and cysteine residues via complex mechanisms to form post-translational modifications known as advanced glycation end-products (AGEs). Glyoxal, methylglyoxal, and 3-deoxyglucosone are the major endogenous dicarbonyls, with methylglyoxal being the most well-studied. There are several routes that lead to the formation of dicarbonyl compounds, most originating from glucose and glucose metabolism, such as the non-enzymatic decomposition of glycolytic intermediates and fructosyl amines. Although dicarbonyls are removed continuously mainly via the glyoxalase system, several conditions lead to an increase in dicarbonyl concentration and thereby AGE formation. AGEs have been implicated in diabetes and aging-related diseases, and for this reason the elucidation of their structure as well as protein targets is of great interest. Though the dicarbonyls and reactive protein side chains are of relatively simple nature, the structures of the adducts as well as their mechanism of formation are not that trivial. Furthermore, detection of sites of modification can be demanding and current best practices rely on either direct mass spectrometry or various methods of enrichment based on antibodies or click chemistry followed by mass spectrometry. Future research into the structure of these adducts and protein targets of dicarbonyl compounds may improve the understanding of how the mechanisms of diabetes and aging-related physiological damage occur.


1998 ◽  
Author(s):  
Rebecca A. Clewell ◽  
Wayne T. Brashear ◽  
David T. Tsui ◽  
Sanwat Chaudhuri ◽  
Rachel S. Cassady

2019 ◽  
Vol 31 (12) ◽  
pp. 2740-2744
Author(s):  
Anil Verma ◽  
Vinod Kumar ◽  
Ramesh Kataria ◽  
Joginder Singh

Eleven acetohydrazide linked pyrazole derivatives were designed and synthesized via condensation of acetohyadrazide with different substituted formyl pyrazole derivatives under mild reaction conditions. Synthesized compounds were characterized on the basis of IR, NMR (1H & 13C) and mass spectrometry. The antimicrobial activities of all the compounds were screened against four bacterial and two fungal strains. Among the synthesized compounds, three compounds viz. 6b, 6c and 6d were found as efficient antimicrobial agents in reference to the standard drugs viz. ciprofloxacin and amphotericin-B. Further, structure-activity relationship (SAR) study revealed that electron-withdrawing group enhances the antimicrobial potential of synthesized derivatives as compared to other groups present in the ring. Hence, among compounds 6b-c, compound 6d could be explored further against other microbes to prove its vitality.


FEBS Letters ◽  
1996 ◽  
Vol 389 (3) ◽  
pp. 309-313 ◽  
Author(s):  
Monica Di Luca ◽  
Lucia Pastorino ◽  
Vittorio Raverdino ◽  
Pierre N.E. De Graan ◽  
Antonio Caputi ◽  
...  

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