Entwicklung von Quantenpunkten und Kolloidaler Goldpartikeln für die selektive Markierung P2Y6-exprimierender Zellen
Zusammenfassung der Projektergebnisse
Within the proposed research project, the development of quantum dots (QD) and gold nanoparticles (AuNPs) for the selective labeling of P2Y6 receptor expressing cells was envisaged. Introduction of poly(amidoamine) dendrons (PAMAM), on the surface of QDs or AuNPs, as a coating and drug linking moieties, anchored to the CdSe/ZnS-core material via a thioctic acid was planned. General structure A of a proposed functionalized quantum dot (QD) or gold nanoparticle (AuNP) with G2.5 PAMAM (terminal carboxylate) dendron. However, due to the chemical instability towards oxidation of PAMAM dendrons, demonstrated recently by Jacobson et al., I have decided to develop Newkome-type dendrons that are known to be stable to oxidative conditions. Furthermore, we have decided to use XAC, a non-selective adenosine (P1) receptor ligand, for dendron functionalization. The advantage of XAC is its chemical stability and an already existing broad pharmacological evaluation in various types of adenosine receptor assays. Furthermore, XAC is offering an amine linker that is insensitive to attachment of large carrier moieties. Pharmacological characterization of QD and AuNPs bearing XAC would provide a proof of principle for the new scaffolds and give a basis for future nanoparticle functionalization with chemically more challenging P2Y6 receptor ligands. The synthesis of functionalized dendrimers turned out to be quite challenging and so far I wasn’t able to complete this project. However, the preliminary results generated so far are quite encouraging and I am continuing this project in close collaboration with Dr. Jacobson.
Projektbezogene Publikationen (Auswahl)
- Structure-Based Design of 3-(4- Aryl-1H-1,2,3-triazol-1-yl)-Biphenyl Derivatives as P2Y14 Receptor Antagonists. J. Med. Chem. 2016, 59, 6149–6168
Junker, A.; Balasubramanian, R.; Ciancetta, A.; Uliassi, E.; Kiselev, E.; Martiriggiano, C.; Trujillo, K.; Mtchedlidze, G.; Birdwell, L.; Brown, K. A.; Harden, T. K.; Jacobson, K. A.
(Siehe online unter https://doi.org/10.1021/acs.jmedchem.6b00044)
