TP10-dopamine conjugate as a potential therapeutic agent in the treatment of Parkinson’s disease

Izabela Rusiecka , Jarosław Ruczyński , Agnieszka Kozłowska , Ewelina Backtrog , Piotr Mucha , Ivan Kocić , Piotr Rekowski


Parkinson’s disease (PD) is a common progressive neurodegenerative disorder for which the current treatment is not fully satisfactory. One of the major drawbacks of current PD therapy is poor penetration of drugs across the blood-brain barrier (BBB). In recent years, cell-penetrating peptides (CPPs) such as Tat, SynB, or TP10 have gained great interest due to their ability to penetrate cell membranes and to deliver different cargos to their targets including the central nervous system (CNS). However, there is no data with respect to the use of CPPs as drug carriers to the brain for the treatment of PD. In the presented research, the covalent TP10-dopamine conjugate was synthesized and its pharmacological properties were characterized in terms of its ability to penetrate the BBB and anti-parkinsonian activity. The results showed that dopamine (DA) in the form of a conjugate with TP10 evidently gained access to the brain tissue, exhibited low susceptibility to O-methylation reaction by catechol-O-methyltransferase (lower than that of DA), possessed a relatively high affinity to both dopamine D1 and D2 receptors (in the case of D1, a much higher than that of DA), and showed antiparkinsonian activity (higher than that of L-DOPA) in the MPTP-induced preclinical animal model of PD. The presented results prove that the conjugation of TP10 with DA may be a good starting point for the development of a new strategy for the treatment of PD.
Author Izabela Rusiecka
Izabela Rusiecka,,
, Jarosław Ruczyński (FCh/DMB/LChBAC)
Jarosław Ruczyński,,
- Laboratory of Chemistry of Biologically Active Compounds
, Agnieszka Kozłowska (FCh/DMB/LChBAC)
Agnieszka Kozłowska,,
- Laboratory of Chemistry of Biologically Active Compounds
, Ewelina Backtrog (FCh/DMB/LChBAC)
Ewelina Backtrog,,
- Laboratory of Chemistry of Biologically Active Compounds
, Piotr Mucha (FCh/DMB/LChBAC)
Piotr Mucha,,
- Laboratory of Chemistry of Biologically Active Compounds
, Ivan Kocić
Ivan Kocić,,
, Piotr Rekowski (FCh/DMB/LChBAC)
Piotr Rekowski,,
- Laboratory of Chemistry of Biologically Active Compounds
Journal seriesBioconjugate Chemistry, ISSN 1043-1802, (N/A 100 pkt)
Issue year2019
Publication size in sheets0.70
Keywords in Polishtransportan 10, dopamina, choroba Parkinsona, bariera krew-mózg, chemia klik
ASJC Classification1605 Organic Chemistry; 3003 Pharmaceutical Science; 3004 Pharmacology; 2204 Biomedical Engineering; 1502 Bioengineering; 1305 Biotechnology
Languageen angielski
Score (nominal)100
Score sourcejournalList
ScoreMinisterial score = 100.0, 28-01-2020, ArticleFromJournal
Publication indicators WoS Citations = 0.000; Scopus SNIP (Source Normalised Impact per Paper): 2018 = 0.991; WoS Impact Factor: 2018 = 4.349 (2) - 2018=4.561 (5)
Citation count*5 (2020-07-16)
Share Share

Get link to the record

* presented citation count is obtained through Internet information analysis and it is close to the number calculated by the Publish or Perish system.
Are you sure?