synthesis of functionalised nucleosides for incorporation into nucleic acid-based serine protease mimics合成functionalised并入核酸丝氨酸蛋白酶模拟核苷.pdfVIP

Molecules 2007, 12, 114-129 molecules ISSN 1420-3049 Full Paper Synthesis of Functionalised Nucleosides for Incorporation into Nucleic Acid-Based Serine Protease Mimics Mieke A. Catry and Annemieke Madder* Ghent University, Department of Organic Chemistry, Laboratory for Organic and Biomimetic Chemistry, Krijgslaan 281 (S4), B-9000 Gent, Belgium. * Author to whom correspondence should be addressed. E-mail: Annemieke.Madder@UGent.be Received: 21 December 2006; in revised form: 29 January 2007 / Accepted: 30 January 2007 / Published: 31 January 2007 Abstract: The synthesis of nucleosides modified with an extra imidazole, carboxyl and hydroxyl group is described. These nucleosides can be incorporated into an oligonucleotide duplex, thus generating a novel type of serine protease mimic. Keywords: Nucleoside synthesis, serine protease mimic, DNA scaffold, 2’ modification. Introduction Enzymes are of great importance in nature because of their ability to catalyse reactions in a selective and efficient way. The development of artificial catalysts which mimic enzymatic activity has always been a very challenging area of research. Among the different enzymes, proteases have been intensively studied because of their unequalled capacity for hydrolysing amide and peptide bonds under mild conditions. One of the most studied serine proteases is α-chymotrypsin, and X-ray diffraction studies give a good insight into the tertiary structure of the enzyme [1-4]. The active site contains three amino acids which are essential for catalysis of the cleavage of amide bonds (Figure 1). T