TP10-Dopamine Conjugate as a Potential Therapeutic Agent in the Treatment of Parkinson's Disease.

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 anti-parkinsonian 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.

Capillary electrophoresis study of systemin peptides spreading in tomato plant.

Systemin (Sys) is an 18-aa plant peptide hormone involved in the regulation of plant's defensive response. Sys is considered as a fast-spreading systemic wound signal. We developed a simple and rapid CE method to monitor the spreading of Sys peptides through tomato plant. A 1,2,3-triazole-linked AZT-systemin conjugate was designed as a model to study the possibility of translocating small cargo molecules 3'-Azido-2',3'-dideoxythymidine by systemin. The Sys peptides (Sys, N-propiolyl Sys, and AZT-systemin conjugate) were injected into the stem and leaves of mature tomato plant. Its transportation throughout the plant tissue was traced by CE. The peptides were clearly visible in the crude tomato exudates and an optimum separation was achieved in 25 mM phosphate "buffer" at pH 2.5 and a voltage of 20 kV using uncoated fused silica capillary. CE analysis showed that Sys peptides are well separated from tomato plant exudates ingredients and are stable in tomato stem and leaf exudates for up to 24 h. CE study revealed that the Sys peptides are effectively spreading throughout tomato stem and leaves and the peptides could be directly detected in the crude plant matrixes. The translocation was strongly inhibited by sodium azide. The results showed that the established CE method can be used to characterize plant peptides spreading under plant physiological conditions.