Title:Current Advances in L-DOPA and DOPA-Peptidomimetics: Chemistry, Applications and Biological Activity
Volume: 22
Issue: 36
Author(s): Bruno Mattia Bizzarri, Silvia Tortolini, Luca Rotelli, Giorgia Botta and Raffaele Saladino
Affiliation:
Keywords:
L-DOPA, Parkinson, peptidomimetics, biological and pharmacological activity, synthesis.
Abstract: L-3,4-Dihydroxyphenylalanine [2-amino-3-(3,4-dihydroxyphenyl) propanoic acid
(L-DOPA) is a natural constituent of animal and plant tissue derived from post-translational
modification of the amino acid tyrosine. L-DOPA is modified during metabolism to
catecholamine neurotransmitters, noradrenaline and adrenaline, which are characterized by
different biological activities. L-DOPA has been the first drug of choice in the therapy of
Parkinson’s disease that is a progressive neurodegenerative disorder involving the loss of
dopaminergic neurons of substantia nigra pars compacta. The social and economic impact of these diseases
is very high due to the progressive aging of the population. This review focuses on the biological effect of LDOPA,
as well as on the synthesis of L-DOPA derivatives and their application in central nervous system diseases.
Among them, L-DOPA-containing peptides (L-DOPA-Pep) show important biological and pharmacological
activities. For example, L-DOPA analogues of the alpha-factor interact with models of the G proteincoupled
receptor, inhibit the oxidation of low-density lipoproteins, and are used for improving L-DOPA absorption
in long-term treatment of Parkinson’s disease and as skin moisturizer in cosmetic compositions.
Moreover, L-DOPA residues in proteins provide reactive tools for the preparation of adhesives and coatings
materials. Usually, L-DOPA-Pep is prepared by traditional liquid or solid state procedures starting from simple
amino acids. Recently, selective side-chain modifications of pre-formed peptides have also been reported
both for linear and branched peptides. Here, we describe the recent advances in the synthesis of L-DOPA and
dopa-peptidomimetics and their biological and pharmacological activities, focusing the attention on new synthetic
procedures and biological mechanism of actions.
