Dopamine D 2 and Serotonin 5-HT 1A Dimeric Receptor-Binding Monomeric Antibody scFv as a Potential Ligand for Carrying Drugs Targeting Selected Areas of the Brain.
Agata KowalikMateusz MajerekKrzysztof MrowiecJoanna SolichFaron-Górecka AgataOlga WoźnickaMarta Dziedzicka-WasylewskaSylwia ŁukasiewiczPublished in: Biomolecules (2022)
Targeted therapy uses multiple ways of ensuring that the drug will be delivered to the desired site. One of these ways is an encapsulation of the drug and functionalization of the surface. Among the many molecules that can perform such a task, the present work focused on the antibodies of single-chain variable fragments (scFvs format). We studied scFv, which specifically recognizes the dopamine D 2 and serotonin 5-HT 1A receptor heteromers. The scFv D2-5-HT1A protein was analyzed biochemically and biologically, and the obtained results indicated that the antibody is properly folded and non-toxic and can be described as low-immunogenic. It is not only able to bind to the D 2 -5-HT 1A receptor heteromer, but it also influences the cAMP signaling pathway and-when surfaced on nanogold particles-it can cross the blood-brain barrier in in vitro models. When administered to mice, it decreased locomotor activity, matching the effect induced by clozapine. Thus, we are strongly convinced that scFvD 2 -5-HT 1A , which was a subject of the present investigation, is a promising targeting ligand with the potential for the functionalization of nanocarriers targeting selected areas of the brain.
Keyphrases
- cancer therapy
- binding protein
- signaling pathway
- white matter
- resting state
- drug delivery
- spinal cord injury
- human health
- drug induced
- epithelial mesenchymal transition
- adverse drug
- emergency department
- transcription factor
- adipose tissue
- metabolic syndrome
- functional connectivity
- climate change
- cell proliferation
- oxidative stress
- risk assessment
- drug release
- protein kinase
- electronic health record