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Amino Acids

, Volume 43, Issue 1, pp 111–126 | Cite as

Transforming dietary peptides in promising lead compounds: the case of bioavailable carnosine analogs

  • Giulio Vistoli
  • Marina Carini
  • Giancarlo AldiniEmail author
Review Article

Abstract

The ability of carnosine to prevent advanced glycoxidation end products (AGEs) and advanced lipoxidation end products (ALEs) formation, on the one hand, and the convincing evidence that these compounds act as pathogenetic factors, on the other hand, strongly support carnosine as a promising therapeutic agent for oxidative-based diseases. The mechanism/s by which carnosine inhibits AGEs and ALEs is still under investigation but an emerging hypothesis is that carnosine acts by deactivating the AGEs and ALEs precursors and in particular the reactive carbonyl species (RCS) generated by both lipid and sugar oxidation. The ability of carnosine to inhibit AGEs and ALEs formation and the corresponding biological effects has been demonstrated in several in vitro studies and in some animal models. However, such effects are in line of principle, limited in humans, due to the effect of serum carnosinase (absent in rodents), which catalyzes the carnosine hydrolysis to its constitutive amino acids. Such a limitation has prompted a great interest in the design of carnosine derivatives, which maintaining (or improving) the reactivity with RCS, are more resistant to carnosinase. The present paper intends to critically review the most recent studies oriented to obtaining carnosine derivatives, optimized in terms of reactivity with RCS, selectivity (no reaction with physiological aldehydes) and the pharmacokinetic profile (mainly through an enhanced resistance to carnosinase hydrolysis). The review also includes a brief description of AGEs and ALEs as drug targets and the evidence so far reported regarding the ability of carnosine as inhibitor of AGEs and ALEs formation and the proposed reaction mechanisms.

Keywords

Carnosine and derivatives thereof Advanced glycoxidation end products (AGEs) Advanced lipoxidation end products (ALEs) Reactive carbonyl species Carbonyl quenching 

Notes

Acknowledgments

This work was supported by funds from the Italian Ministry of University and Research (PRIN 2007 and 2009) and from the Regione Lombardia-MIUR (L.297—Art. 12/BioTech DM27909).

Conflict of interest

The Authors are co-inventors of patents related to some of the carnosine derivatives included in the present review and they are partially supported by Flamma S.p.a.

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Copyright information

© Springer-Verlag 2012

Authors and Affiliations

  • Giulio Vistoli
    • 1
  • Marina Carini
    • 1
  • Giancarlo Aldini
    • 1
    Email author
  1. 1.Department of Pharmaceutical Sciences “Pietro Pratesi”Università degli Studi di MilanoMilanItaly

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