With Nucleoside Analogues Of The Protein Functional Groups Design, Synthesis,

As is well known that cell functions come from continuous and tremendous recognition and chemical interactions between macromolecules and/or small molecules. While the chemical groups responsible for the interactions is the most important consideration to understand these processes, natural or pathologically, occurring in organisms. Three dimensional mimicking of the chemical functional groups in an appropriate scaffold is one of the ways for the investigations.In our research on biomolecular recognition and interactions, helical nucleic acid structures and the residues were used for the mimicking of functional domains of biomolecules. Compared with proteins usually used in this kind of research, nucleic acid holds advantages with its relatively regular helical structures, recoverable and stable properties over proteins. But its poor active functional groups is not compatible with this project. Introduction of proteinic functional groups into nucleic acid (base, sugar, or phosphate) and their compositions in the helical structure according to computer-aided mimicking of biomolecules will be a completely new way to study the biomolecular interactions.In this work of the project, the well-understood chymotripson were chosen for the structural and functional simulation. Firstly, we designed and synthesized the phosphoramidites 1-8 bearing hydroxyl, imidazolyl, and hydrophobic groups constituting the catalytic domain of chymotripson, which can then be used for solid-phase synthesis of oligodeoxynucleotides for the structural and functional simulations of the target enzyme and other biomolecules. In the 5-position of 2'-deoxyuridine, 3-hydroxypropynyl (BWX3), 4-ethenylimidazolyl (BWX4), phenylacetynyl (BWXl), and phenylethyl (BWX2) were introduced; in the 7-position of 8-aza-7-deaza-2'-deoxyadenosine, 3-hydroxypropynyl (BWX7), 3-hydroxypropyl (BWX8), phenylacetynyl (BWX5), and phenylethyl (BWX6) were introduced. In the synthesis of these target compounds, the preparation of several important intermediates were optimized.