Larryn W Peterson

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An unnatural base-pair architecture with base pairs 2.4 Å larger than the natural DNA-based genetic system (xDNA) is evaluated for its ability to function like DNA, encoding amino acids in the context of living cells. xDNA bases are structurally analogous to natural bases but homologated by the width of a benzene ring, increasing their sizes and resulting(More)
Nucleotide analogues have been well accepted as therapeutic agents active against a number of viruses. However, their use as antiviral agents is limited by the need for phosphorylation by endogenous enzymes, and if the analogue is orally administered, by low bioavailability due to the presence of an ionizable diacid group. To circumvent these limitations, a(More)
Cidofovir (HPMPC, 1), a broad-spectrum antiviral agent, is currently used to treat AIDS-related human cytomegalovirus (HCMV) retinitis and has recognized therapeutic potential for orthopox virus infections, but is limited by its low oral bioavailability. Cyclic cidofovir (2) displays decreased nephrotoxicity compared to 1, while also exhibiting potent(More)
We report the synthesis and biological evaluation of Ala-(Val-)l-Ser-CO(2)R prodrugs of 1, where a dipeptide promoiety is conjugated to the P(OH)(2) group of cidofovir (1) via esterification by the Ser side chain hydroxyl group and an ethyl group (4 and 5) or alone (6 and 7). In a murine model, oral administration of 4 or 5 did not significantly increase(More)
Eight novel single amino acid (6-11) and dipeptide (12, 13) tyrosine P-O esters of cyclic cidofovir ((S)-cHPMPC, 4) and its cyclic adenine analogue ((S)-cHPMPA, 3) were synthesized and evaluated as prodrugs. In vitro IC(50) values for the prodrugs (<0.1-50 μM) vs vaccinia, cowpox, human cytomegalovirus, and herpes simplex type 1 virus were compared to those(More)
Abnormal replication of DNA is associated with many important human diseases, most notably viral infections and neoplasms. Existing approaches to chemotherapeutics for diseases associated with dysfunctional DNA replication classically involve nucleoside analogues that inhibit polymerase activity due to modification in the nucleobase and/or ribose moieties.(More)
Cidofovir (HPMPC) is a broad-spectrum antiviral agent, currently used to treat AIDS-related human cytomegalovirus retinitis. Cidofovir has recognized therapeutic potential for orthopox virus infections, although its use is hampered by its inherent low oral bioavailability. Val-Ser-cyclic HPMPC (Val-Ser-cHPMPC) is a promising peptide prodrug which has(More)
The design of smart nonviral vectors for gene delivery is of prime importance for the successful implementation of gene therapies. In particular, degradable analogues of macromolecules represent promising targets as they would combine the multivalent presentation of multiple binding units that is necessary for achieving effective complexation of therapeutic(More)
Cidofovir (HPMPC), a broad spectrum antiviral agent, cannot be administered orally due to ionization of its phosphonic acid group at physiological pH. One prodrug approach involves conversion to the cyclic form (cHPMPC, 1) and esterification by the side chain hydroxyl group of a peptidomimetic serine. Transport studies in a rat model have shown enhanced(More)