title: Current Advances in L-DOPA and DOPA-Peptidomimetics: Chemistry, Applications and Biological Activity.
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 protein-coupled 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.
authors.forename: Bruno Mattia
authors.initials: BM
authors.lastname: Bizzarri
authors.forename: Silvia
authors.initials: S
authors.lastname: Tortolini
authors.forename: Luca
authors.initials: L
authors.lastname: Rotelli
authors.forename: Giorgia
authors.initials: G
authors.lastname: Botta
authors.affiliation: Dipartimento di Ecologia e Biologia, University of Tuscia, Via S. Camillo de Lellis snc, 01100 Viterbo Italy. saladino@unitus.it.
authors.forename: Raffaele
authors.initials: R
authors.lastname: Saladino
mesh_terms: D004298:Dopamine / Q000378:metabolism; D059290:Dopaminergic Neurons / Q000187:drug effects / Q000378:metabolism; D020820:Dyskinesias / Q000188:drug therapy / Q000473:pathology; D006801:Humans; D007980:Levodopa / Q000031:analogs & derivatives* / Q000138:chemical synthesis / Q000627:therapeutic use; D018384:Oxidative Stress / Q000187:drug effects; D010300:Parkinson Disease / Q000188:drug therapy / Q000378:metabolism / Q000473:pathology; D010455:Peptides / Q000737:chemistry*; D057786:Peptidomimetics; D011355:Prodrugs / Q000138:chemical synthesis / Q000494:pharmacology / Q000627:therapeutic use
chemical_list: D010455:Peptides; D057786:Peptidomimetics; D011355:Prodrugs; D007980:Levodopa; D004298:Dopamine