Author(s): Tomar R; Ghodke PP; Patra A; Smyth E; Pontarelli A; Copp W; Guengerich FP; Chaput JJ; Wilds CJ; Stone MP; Egli M;

a-l-(3'-2')-Threofuranosyl nucleic acid (TNA) pairs with itself, cross-pairs with DNA and RNA, and shows promise as a tool in synthetic genetics, diagnostics, and oligonucleotide therapeutics. We studied in vitro primer insertion and extension reactions catalyzed by human trans-lesion syn ...

Article GUID: 39259676

Author(s): Kozlov G; Jiang J; Rutherford T; Noronha AM; Wilds CJ; Gehring K;

La-related proteins (LARPs) are a family of RNA-binding proteins that share a conserved La motif (LaM) domain. LARP1 plays a role in regulating ribosomal protein synthesis and stabilizing mRNAs and has a unique structure without an RNA binding RRM domain adjoining the LaM domain. In this study, we investigated the physical basis for LARP1 specificity for ...

Article GUID: 39016322

Author(s): Ayan S; Rotaru AM; Kaye EG; Juneau G; Das S; Wilds CJ; Beharry AA;

Fluorescent chemosensors offer a direct means of measuring enzyme activity for cancer diagnosis, predicting drug resistance, and aiding in the discovery of new anticancer drugs. O6-methylguanine DNA methyltransferase (MGMT) is a predictor of resistance towards anticancer alkylating agents such as temozolomide. Using the fluorescent molecular rotor, 9-(2-c ...

Article GUID: 38502038

Author(s): Pontarelli A; Wilds CJ;

The clinical success of the antisense approach for the treatment of genetic disorders is indisputably the result of chemical modifications along the oligonucleotide (ON) scaffold, which impart desirable properties including high RNA affinity, nuclease stability and improved drug delivery. While effective, many modifications are not capable of eliciting an ...

Article GUID: 37667655

Author(s): Pontarelli A; Wilds CJ;

The introduction of chemical modifications on the nucleic acid scaffold has allowed for the progress of antisense oligonucleotides (ASOs) in the clinic for the treatment of a variety of disorders. In contribution to the repertoire of gene-silencing nucleic acid modifications, herein we report the synthesis and incorporation of C5-propynyl arabinouridine ( ...

Article GUID: 36857293

Author(s): Pontarelli A; Liu JT; Oh JK; Wilds CJ;

The protocols described in this article provide details regarding the synthesis and characterization of a disulfide containing linker phosphoramidite for terminal functionalization of synthetic oligonucleotides. The linker is first synthesized from 6-mercaptohexanol in two steps and is incorporated at the 5' end of short DNA oligonucleotides using aut ...

Article GUID: 36840706

Author(s): Kozlov G; Mattijssen S; Jiang J; Nyandwi S; Sprules T; Iben JR; Coon SL; Gaidamakov S; Noronha AM; Wilds CJ; Maraia RJ; Gehring K;

La-related proteins (LARPs) comprise a family of RNA-binding proteins involved in a wide range of posttranscriptional regulatory activities. LARPs share a unique tandem of two RNA-binding domains, La motif (LaM) and RNA recognition motif (RRM), together referred to as a La-module, but vary in mem ...

Article GUID: 35979957

Author(s): Pontarelli A; Liu JT; Movasat H; Ménard S; Oh JK; Wilds CJ;

The synthesis and incorporation of a tosylated phosphoramidite linker containing a disulfide bond is described. Incorporation of the linker into short DNA and RNA oligomers proceeded efficiently using automated solid phase synthesis. Treatment of the support bound oligonucleotide followed by cleavage from the solid support provided a variety of common fun ...

Article GUID: 35863757

Author(s): Pontarelli A; Wilds CJ;

The promise of the antisense approach to treat a variety of diseases with oligonucleotides and solutions to challenges that have been encountered in their development is attributable to chemical modification of the nucleic acid scaffold. Herein, we describe preliminary data regarding the synthesis of a novel C5-propynyl-ß-D-arabinouridine (araUP) phosphor ...

Article GUID: 35452799

Author(s): Liczner C; Hanna CC; Payne RJ; Wilds CJ;

A breadth of strategies are needed to efficiently modify oligonucleotides with peptides or lipids to capitalize on their therapeutic and diagnostic potential, including the modulation of in vivo chemical stability and for applications in cell-targeting and cell-permeability. The chemical linkages typically used in peptide oligonucleotide conjugates (POCs) ...

Article GUID: 35126973

Author(s): Liczner C; Duke K; Juneau G; Egli M; Wilds CJ;

Over the past 25 years, the acceleration of achievements in the development of oligonucleotide-based therapeutics has resulted in numerous new drugs making it to the market for the treatment of various diseases. Oligonucleotides with alterations to their scaffold, prepared with modified nucleosides and solid-phase synthesis, have yielded molecules with in ...

Article GUID: 33981365