Synthetic oligoribonucleotides carrying site-specific modifications for RNA structure-function analysis

A Rearrangement of the Guanosine-Binding Site Establishes an Extended Network of Functional Interactions in the Tetrahymena Group I Ribozyme Active Site

“…Chemical biology probes, based on site-specific modifications of the RNA backbone and its nucleobases, are invaluable tools for testing and extending models and proposals derived from structural approaches ,− . Further, as illustrated herein, functional studies can provide information about the conformational transitions and the connectivity of interactions that are used to establish active sites and precisely position substrates and active site groups (e.g., refs and − ).…”

A Rearrangement of the Guanosine-Binding Site Establishes an Extended Network of Functional Interactions in the Tetrahymena Group I Ribozyme Active Site

“…Chemical biology probes, based on site-specific modifications of the RNA backbone and its nucleobases, are invaluable tools for testing and extending models and proposals derived from structural approaches ,− . Further, as illustrated herein, functional studies can provide information about the conformational transitions and the connectivity of interactions that are used to establish active sites and precisely position substrates and active site groups (e.g., refs and − ).…”

The Hydrolysis of RNA: From Theoretical Calculations to the Hammerhead Ribozyme-Mediated Cleavage of RNA

“…A major advantage of chemically synthesized ribozymes is that site-specific modi-fications can be introduced at any position in the molecule. [250][251][252][253] This approach provides flexibility in the design of ribozymes that have wild-type catalytic activity and are not cleaved by nucleases.…”

“…Trans -acting ribozymes exert their activity in a highly specific manner and they are, therefore, not expected to have negative effects on nontargeted cellular functions. , Because of this specificity, the concept of exploiting ribozymes for cleavage of a specific target mRNA is now emerging as a therapeutic strategy in human diseases such as cancer and AIDS. ,− For ribozymes to function as therapeutic agents, they must be introduced exogenously or produced endogenously in the target cells. , In the former case, the chemically modified ribozyme must maintain its catalytic activity while also being resistant to nucleases. A major advantage of chemically synthesized ribozymes is that site-specific modifications can be introduced at any position in the molecule. − This approach provides flexibility in the design of ribozymes that have wild-type catalytic activity and are not cleaved by nucleases.…”

Comparative analysis of hairpin ribozyme structures and interference data

“…All of the unexplained interferences cluster around the scissile phosphate in a pocket formed by the conserved residues G+1, A9, A10, C25 and A38 (12). All of the functional groups that point into this cavity are required for catalysis, including the N2 amine of G+1, the N6 amine of A38, and the N1 imino group of A10 (2,13,15). Furthermore, occupation of this cavity by methylation of the N6 amine of A9 significantly disrupts activity (13).…”

A Rearrangement of the Guanosine-Binding Site Establishes an Extended Network of Functional Interactions in the Tetrahymena Group I Ribozyme Active Site

“…Chemical biology probes, based on site-specific modifications of the RNA backbone and its nucleobases, are invaluable tools for testing and extending models and proposals derived from structural approaches ,− . Further, as illustrated herein, functional studies can provide information about the conformational transitions and the connectivity of interactions that are used to establish active sites and precisely position substrates and active site groups (e.g., refs and − ).…”

The Hydrolysis of RNA: From Theoretical Calculations to the Hammerhead Ribozyme-Mediated Cleavage of RNA

“…A major advantage of chemically synthesized ribozymes is that site-specific modi-fications can be introduced at any position in the molecule. [250][251][252][253] This approach provides flexibility in the design of ribozymes that have wild-type catalytic activity and are not cleaved by nucleases.…”

“…Trans -acting ribozymes exert their activity in a highly specific manner and they are, therefore, not expected to have negative effects on nontargeted cellular functions. , Because of this specificity, the concept of exploiting ribozymes for cleavage of a specific target mRNA is now emerging as a therapeutic strategy in human diseases such as cancer and AIDS. ,− For ribozymes to function as therapeutic agents, they must be introduced exogenously or produced endogenously in the target cells. , In the former case, the chemically modified ribozyme must maintain its catalytic activity while also being resistant to nucleases. A major advantage of chemically synthesized ribozymes is that site-specific modifications can be introduced at any position in the molecule. − This approach provides flexibility in the design of ribozymes that have wild-type catalytic activity and are not cleaved by nucleases.…”

Comparative analysis of hairpin ribozyme structures and interference data

“…All of the unexplained interferences cluster around the scissile phosphate in a pocket formed by the conserved residues G+1, A9, A10, C25 and A38 (12). All of the functional groups that point into this cavity are required for catalysis, including the N2 amine of G+1, the N6 amine of A38, and the N1 imino group of A10 (2,13,15). Furthermore, occupation of this cavity by methylation of the N6 amine of A9 significantly disrupts activity (13).…”

A Rearrangement of the Guanosine-Binding Site Establishes an Extended Network of Functional Interactions in the Tetrahymena Group I Ribozyme Active Site

“…Chemical biology probes, based on site-specific modifications of the RNA backbone and its nucleobases, are invaluable tools for testing and extending models and proposals derived from structural approaches ,− . Further, as illustrated herein, functional studies can provide information about the conformational transitions and the connectivity of interactions that are used to establish active sites and precisely position substrates and active site groups (e.g., refs and − ).…”

The Hydrolysis of RNA: From Theoretical Calculations to the Hammerhead Ribozyme-Mediated Cleavage of RNA

“…A major advantage of chemically synthesized ribozymes is that site-specific modi-fications can be introduced at any position in the molecule. [250][251][252][253] This approach provides flexibility in the design of ribozymes that have wild-type catalytic activity and are not cleaved by nucleases.…”

“…Trans -acting ribozymes exert their activity in a highly specific manner and they are, therefore, not expected to have negative effects on nontargeted cellular functions. , Because of this specificity, the concept of exploiting ribozymes for cleavage of a specific target mRNA is now emerging as a therapeutic strategy in human diseases such as cancer and AIDS. ,− For ribozymes to function as therapeutic agents, they must be introduced exogenously or produced endogenously in the target cells. , In the former case, the chemically modified ribozyme must maintain its catalytic activity while also being resistant to nucleases. A major advantage of chemically synthesized ribozymes is that site-specific modifications can be introduced at any position in the molecule. − This approach provides flexibility in the design of ribozymes that have wild-type catalytic activity and are not cleaved by nucleases.…”

Comparative analysis of hairpin ribozyme structures and interference data

“…All of the unexplained interferences cluster around the scissile phosphate in a pocket formed by the conserved residues G+1, A9, A10, C25 and A38 (12). All of the functional groups that point into this cavity are required for catalysis, including the N2 amine of G+1, the N6 amine of A38, and the N1 imino group of A10 (2,13,15). Furthermore, occupation of this cavity by methylation of the N6 amine of A9 significantly disrupts activity (13).…”