This subproject is one of many research subprojects utilizing theresources provided by a Center grant funded by NIH/NCRR. The subproject andinvestigator (PI) may have received primary funding from another NIH source,and thus could be represented in other CRISP entries. The institution listed isfor the Center, which is not necessarily the institution for the investigator.Our long-term goal is to develop a variety of multi-functional nanostructured materials for biomedical applications. In the short-term, for the period covered by this application, we intend to enhance our understanding of the fundamental principles that modulate the self-assembly of guanine derivatives into functional nanostructures such as dendrimers. Therefore, the specific aims for this application are: (1) To synthesize and characterize appropriately derivatized 8-arylguanine analogues (8ArGs), (2) to construct self-assembled dendrimers (SADs) using 8ArGs as building blocks, and (3) to elucidate the supramolecular behavior (thermodynamics and kinetics) of such SADs, in particular their host-guest properties with molecules of biomedical importance. The rationale and intellectual merit of the proposed studies is that they will reveal important fundamental knowledge on the principles and rules that allow the self-assembly (and disassembly) of guanine derivatives into dendrimers. The proposed research builds on recent discoveries from our laboratory on how the self-assembly properties of 8ArGs can be modulated by the nature of a group attached to the C8 of the guanine base. Our research team is well-qualified to conduct this project because of our: (i) expertise with the synthesis and characterization of a variety of 8ArGs and their resulting quadruplexes; (ii) preliminary data demonstrating that the behavior of quadruplexes can be modulated by the structure of the 8ArGs building blocks. The proposed research is innovative because, for the first time, guanine analogues will be used to construct self-assembled dendrimers for biomedical applications. Our expectations are that, at the conclusion of this research, we will have a good understanding on the use of 8ArGs building blocks for the efficient construction of SADs. We should also be able to use such SADs as receptors and carriers for molecules of biomedical relevance.
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