Date of Award
2020
Document Type
Thesis
Degree Name
MS in Chemistry
Department
Chemistry
First Advisor
Steven Graham
Second Advisor
Joseph Serafin
Third Advisor
Philips Lukeman
Abstract
N1-cyclic inosine 5’-diphosphate ribose, another class of the well-known calcium second messenger cyclic adenosine 5’-diphospate ribose, reveals nearly identical concentration-response calcium releasing activity intracellularly in a Jurkat T-cells (JTC) system. In this study, a three steps synthetic route is proposed to synthesize cIDPR analog 8-bromo-N1-cIDPR (8-Br-N1-cIDPR), the first 8-substitued analog has agonistic activity. The structure-activity relationship (SAR) of this messenger was investigated by the knowledge of its conformational landscapes, determined by variable-temperature NMR spectroscopy, in conjunction with PSEUROT and population analysis, allowing the study of thermodynamic parameters. A pure in-phase (PIP) heteronuclear correlation NMR experiment was adopted for direct extraction of coupling constants of non-first order proton signals. 8-Br-N1-cIDPR in many ways shows the opposite thermodynamics compared to cADPR analogs, despite its clear agonistic behavior.
Recommended Citation
Lyu, Wenjie, "Synthesis, Conformational Analysis, and Thermodynamic Study of N1-cyclic Inosine Diphosphate Ribose and Its Analogs: Towards the SAR of a Calcium Ion Releasing Second Messenger" (2020). Theses and Dissertations. 119.
https://scholar.stjohns.edu/theses_dissertations/119