SYNTHESIS OF POLYRIBONUCLEOTIDES OF DEFINED SEQUENCE

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An automated solid phase system for the rapid synthesis of oligoribonucleotides will be developed. it will use the o- nitrobenzyl group for protection of ribonucleoside 2' hydroxyls and a versatile glass-based support incorporating a novel linker mechanism. New analytical methods will be designed for RNA oligomers, to ascertain their purity and confirm their homogeneity with respect to the 3'-5' linkage. The synthetic methods will first be employed to prepare a number of sets of oligonucleotides as models for the study of RNA hairpin structures, using UV and NMR spectroscopy, and X-ray crystallography. This investigation will focus on the effects of loop sequence and size on hairpin shape and stability. The solid phase system will also be adapted to provide special oligonucleotides that can be joined enzymatically to produce large RNA molecules for the study of more complex secondary structure. The oligonucleotides will carry novel terminal protecting groups to bring about the desired specific ligations. The results of these investigations are expected to contribute to methods for prediction of the secondary structures of ribonucleic acids from their sequences, and should aid studies of structure- function relationships in human RNA viruses.