Propyl Linker Research Articles

Base and sugar requirements for RNA cleavage of essential nucleoside residues in internal loop B of the hairpin ribozyme: implications for secondary structure.

The hairpin ribozyme is a small self-cleaving RNA that can be engineered for RNA cleavage in trans and has potential as a therapeutic agent. We have used a chemical synthesis approach to study the requirements of hairpin RNA cleavage for sugar and base moieties in residues of internal loop B, an essential region in one of the two ribozyme domains. Individual nucleosides were substituted by either a 2'-deoxy-nucleoside, an abasic residue, or a C3-spacer (propyl linker) and the abilities of the modified ribozymes to cleave an RNA substrate were studied in comparison with the wild-type ribozyme. From these results, together with previous studies, we propose a new model for the potential secondary structure of internal loop B of the hairpin ribozyme.

Self-Assembled Monolayers of Alkanethiolates Presenting Tri(propylene sulfoxide) Groups Resist the Adsorption of Protein

Self-Assembled Monolayers of Alkanethiolates Presenting Tri(propylene sulfoxide) Groups Resist the Adsorption of Protein

Synthesis and conformational analysis of pyrimidine nucleoside analogues with a rigid sugar moiety

In order to obtain rigidity within the sugar moiety of nucleosides, some bicyclic pyrimidine nucleoside analogues were synthesized starting from cyclopentanone. The C-3′ is fused to C-4′ via a propylene linker in order to obtain a [3.3.0]-bicyclic ring system wherein the sugar moiety should be restricted to mainly the C-1′-exo conformation.

Enhanced sequence specific recognition in the minor groove of DNA by covalent peptide dimers: bis(pyridine-2-carboxamidonetropsin)(CH2)3-6

The designed peptide pyridine-2-carboxamidonetropsin (2-PyN) binds to the minor groove of double-helical DNA at two very different sequences, 5'-TTTTT-3' and 5'-TGTCA-3', with comparable energetics but quite different structures. 2-PyN likely binds the 5'-TTTTT-3' site as a 1:1 complex, whereas 2-PyN binds 5'-TGTCA-3' sites as a 2:1 complex. In order to enhance the binding affinity of 2-PyN for the 5'-TGTCA-3' site, covalently linked dimers of 2-PyN have been synthesized wherein the nitrogens of the central pyrroles are connected with propyl, butyl, pentyl, and hexyl linkers. DNase I footprint titration experiments reveal that these bis(pyridine-2-carboxamidenetropsin)(CH_2)_(3-6) peptides bind to a 5'-TGTCA-3' site with binding affinities 10-fold greater than that of 2-PyN. By taking advantage of the different structures of peptides bound in the minor groove, the ratio of binding affinities of 2-PyN for 5'-TGTCA-3' and 5'-TTTTT-3' sites have been altered from 1:1 to 25:1.

Structural analysis of covalent peptide dimers, bis(pyridine-2-carboxamidonetropsin)(CH2)3-6, in complex with 5'-TGACT-3' sites by two-dimensional NMR

The peptide pyridine-2-carboxamidonetropsin (2-PyN) binds specifically in the minor groove of 5'-(A,T)G(A,T)C(A,T)-3' sequences as a side-by-side antiparallel dimer. Tethering two 2-PyN ligands through the nitrogens of the central pyrrole rings with propyl, butyl, pentyl and hexyl linkers affords covalent peptide dimers, bis(pyridine-2-carboxamide-netropsin)(CH_2)_(3-6), which bind in the minor groove of DNA with increased binding affinities and improved sequence specificities. Two-dimensional NMR studies of the complexes formed upon binding of these covalent peptide dimers to an oligonucleotide containing a 5'-TGACT-3' site reveal that the dimeric peptides bind as intramolecular dimers with nearly identical geometry and peptide-DNA contacts as in the (2-PyN)_2•5'-TGACT-3' complex.