Changed reactivity of secondary hydroxy groups in C8-modified adenosine – lessons learned from silylation

Synthesis of site-specifically modified oligonucleotides has become a major tool for RNA structure and function studies. Reporter groups or specific functional entities are required to be attached at a pre-defined site of the oligomer. An attractive strategy is the incorporation of suitably functionalized building blocks that allow post-synthetic conjugation of the desired moiety. A C8-alkynyl-modified adenosine derivative was synthesized, reviving an old synthetic pathway for iodination of purine nucleobases. Silylation of the C8-alkynyl-modified adenosine revealed unexpected selectivity of the two secondary sugar hydroxy groups, with the 3'-O-isomer being preferentially formed. Optimization of the protection scheme lead to a new and economic route to the desired C8-alkynylated building block and its incorporation in RNA.

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Changed reactivity of secondary hydroxyl groups in C8-modified adenosine – lessons learned from silylation

10.3762/bxiv.2020.102.v1 ◽

2020 ◽

Author(s):

Jennifer Frommer ◽

Sabine Müller

Keyword(s):

Building Block ◽

Rna Structure ◽

Building Blocks ◽

Structure And Function ◽

Lessons Learned ◽

Hydroxyl Groups ◽

Modified Oligonucleotides ◽

Secondary Hydroxyl ◽

Protection Scheme ◽

And Function

Synthesis of site-specifically modified oligonucleotides has become a major tool for RNA structure and function studies. Reporter groups or specific functional entities are required to be attached at a pre-defined site of the oligomer. An attractive strategy is the incorporation of suitably functionalized building blocks that allow post-synthetic conjugation of the desired moiety. A C8-alkynyl modified adenosine derivative was synthesized, reviving an old synthetic pathway for iodination of purine nucleobases. Silylation of the C8-alkynyl modified adenosine revealed unexpected selectivity of the two secondary sugar hydroxyl groups, with the 3'-O-isomer being preferentially formed. Optimization of the protection scheme lead to a new and economic route to the desired C8-alkynylated building block and its incorporation in RNA.

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Bioelectrocatalytic hydrogels from electron-conducting metallopolypeptides coassembled with bifunctional enzymatic building blocks

Proceedings of the National Academy of Sciences ◽

10.1073/pnas.0805249105 ◽

2008 ◽

Vol 105 (40) ◽

pp. 15275-15280 ◽

Cited By ~ 56

Author(s):

Ian R. Wheeldon ◽

Joshua W. Gallaway ◽

Scott Calabrese Barton ◽

Scott Banta

Keyword(s):

Polyphenol Oxidase ◽

Building Block ◽

Leucine Zipper ◽

Electrical Contact ◽

Building Blocks ◽

Coiled Coils ◽

Biofuel Cell ◽

Random Coil ◽

Catalytic Current ◽

And Function

Here, we present two bifunctional protein building blocks that coassemble to form a bioelectrocatalytic hydrogel that catalyzes the reduction of dioxygen to water. One building block, a metallopolypeptide based on a previously designed triblock polypeptide, is electron-conducting. A second building block is a chimera of artificial α-helical leucine zipper and random coil domains fused to a polyphenol oxidase, small laccase (SLAC). The metallopolypeptide has a helix–random-helix secondary structure and forms a hydrogel via tetrameric coiled coils. The helical and random domains are identical to those fused to the polyphenol oxidase. Electron-conducting functionality is derived from the divalent attachment of an osmium bis-bipyrdine complex to histidine residues within the peptide. Attachment of the osmium moiety is demonstrated by mass spectroscopy (MS-MALDI-TOF) and cyclic voltammetry. The structure and function of the α-helical domains are confirmed by circular dichroism spectroscopy and by rheological measurements. The metallopolypeptide shows the ability to make electrical contact to a solid-state electrode and to the redox centers of modified SLAC. Neat samples of the modified SLAC form hydrogels, indicating that the fused α-helical domain functions as a physical cross-linker. The fusion does not disrupt dimer formation, a necessity for catalytic activity. Mixtures of the two building blocks coassemble to form a continuous supramolecular hydrogel that, when polarized, generates a catalytic current in the presence of oxygen. The specific application of the system is a biofuel cell cathode, but this protein-engineering approach to advanced functional hydrogel design is general and broadly applicable to biocatalytic, biosensing, and tissue-engineering applications.

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Applications of synthetic oligoribonucleotide analogues in studies of RNA structure and function

Journal of Chemical Sciences ◽

10.1007/bf02841914 ◽

1994 ◽

Vol 106 (5) ◽

pp. 1003-1022

Author(s):

Jane A. Grasby ◽

Clare E. Pritchard ◽

Michael J. Gait

Keyword(s):

Rna Structure ◽

Structure And Function ◽

And Function

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Role of Docosahexaenoic Acid in Determining Membrane Structure and Function: Lessons Learned from Normal and Neoplastic Leukocytes

Fatty Acids ◽

10.1385/1-59259-119-1:41 ◽

2003 ◽

pp. 41-62

Author(s):

Laura J. Jenski ◽

William Stillwell

Keyword(s):

Docosahexaenoic Acid ◽

Membrane Structure ◽

Structure And Function ◽

Lessons Learned ◽

Membrane Structure And Function ◽

And Function

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Structure and Function of Multimeric G-Quadruplexes

Molecules ◽

10.3390/molecules24173074 ◽

2019 ◽

Vol 24 (17) ◽

pp. 3074 ◽

Cited By ~ 25

Author(s):

Sofia Kolesnikova ◽

Edward A. Curtis

Keyword(s):

Nucleic Acid ◽

Building Blocks ◽

Structure And Function ◽

Limited Information ◽

Functional Elements ◽

Future Studies ◽

And Function ◽

Nucleic Acid Structures ◽

Sequence Requirements ◽

Order Structures

G-quadruplexes are noncanonical nucleic acid structures formed from stacked guanine tetrads. They are frequently used as building blocks and functional elements in fields such as synthetic biology and also thought to play widespread biological roles. G-quadruplexes are often studied as monomers, but can also form a variety of higher-order structures. This increases the structural and functional diversity of G-quadruplexes, and recent evidence suggests that it could also be biologically important. In this review, we describe the types of multimeric topologies adopted by G-quadruplexes and highlight what is known about their sequence requirements. We also summarize the limited information available about potential biological roles of multimeric G-quadruplexes and suggest new approaches that could facilitate future studies of these structures.

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