Exploring the space of histidine containing dipeptides in search of novel efficient RCS sequestering agents.

Details

Serval ID
serval:BIB_F0ED3342AF38
Type
Article: article from journal or magazin.
Collection
Publications
Institution
Title
Exploring the space of histidine containing dipeptides in search of novel efficient RCS sequestering agents.
Journal
European Journal of Medicinal Chemistry
Author(s)
Vistoli G., De Maddis D., Straniero V., Pedretti A., Pallavicini M., Valoti E., Carini M., Testa B., Aldini G.
ISSN
1768-3254 (Electronic)
ISSN-L
0223-5234
Publication state
Published
Issued date
2013
Peer-reviewed
Oui
Volume
66
Pages
153-160
Language
english
Notes
Publication types: Journal Article
Abstract
The study reports a set of forty proteinogenic histidine-containing dipeptides as potential carbonyl quenchers. The peptides were chosen to cover as exhaustively as possible the accessible chemical space, and their quenching activities toward 4-hydroxy-2-nonenal (HNE) and pyridoxal were evaluated by HPLC analyses. The peptides were capped at the C-terminus as methyl esters or amides to favor their resistance to proteolysis and diastereoisomeric pairs were considered to reveal the influence of configuration on quenching. On average, the examined dipeptides are less active than the parent compound carnosine (βAla + His) thus emphasizing the unfavorable effect of the shortening of the βAla residue as confirmed by the control dipeptide Gly-His. Nevertheless, some peptides show promising activities toward HNE combined with a remarkable selectivity. The results emphasize the beneficial role of aromatic and positively charged residues, while negatively charged and H-bonding side chains show a detrimental effect on quenching. As a trend, ester derivatives are slightly more active than amides while heterochiral peptides are more active than their homochiral diastereoisomer. Overall, the results reveal that quenching activity strongly depends on conformational effects and vicinal residues (as evidenced by the reported QSAR analysis), offering insightful clues for the design of improved carbonyl quenchers and to rationalize the specific reactivity of histidine residues within proteins.
Pubmed
Web of science
Create date
20/09/2013 17:34
Last modification date
20/08/2019 16:18
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