The process by which RNA folds into a three-dimensional structure will be probed by the use of oligoribonucleotides containing alkyl thiol tethers. These tethers will be used to form disulfide cross-links, which allow mapping of the folding pathways of these macromolecules. These studies will define the general principles that govern ribonucleotide folding. In the course of this research, the following topics will be addressed: (1) The design and synthesis of unique RNA nucleosides that possess thiol tethers; (2) Incorporation of thiol-modified nucleosides into oligoribonucleotides by synthesizing several key RNA structural units; and (3) Mapping of the folding pathway of tRNA-Phe through disulfide bond trapping of folding intermediates. %%% This grant from the Organic Dynamics Program supports the work of Professor Gary D. Glick of the University of Michigan. Functions of the important biomolecule RNA are mediated by the manner in which it is folded. This research will seek to define the principles that guide RNA folding and thereby will aid in predicting structure of this macromolecule and its function from the sequence of bases in RNA. The pathways of folding will be mapped by the use of derivatives of RNA whereby sulfur-sulfur bonds can be formed as markers. The research will be involve the synthesis of these RNA derivatives and the determination of the structures of intermediates in the folding process.
