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Selection of 2′-fluoro-modified aptamers with optimized properties

D. Thirunavukarasu, T. Chen, Z. Liu, N. Hongdilokkul, F.E. Romesberg, J. Am. Chem. Soc. (Comm.) (2017) 139:2892–2895.
pubpic2017thirunavukarasuWe report the selection and characterization of 2′-F purine aptamers that bind human neutrophil elastase (HNE) with reasonable affinity. The 2′-F substituents are found to facilitate the selection of specific interactions, and we demonstrate than only a few can optimize properties far beyond simple nuclease resistance.

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Chemical stabilization of unnatural nucleotide triphosphates for the in vivo expansion of the genetic alphabet

A.W. Feldman, V.T. Dien, F.E. Romesberg, J. Am. Chem. Soc. (2017) 139:2464–2467.
pubpic2017feldmanWe report the synthesis and evaluation of unnatural triphosphates with their β,γ-bridging oxygen replaced with a difluoromethylene moiety, yielding dNaMTPCF2 and dTPT3TPCF2. We find that although dNaMTPCF2 cannot support in vivo replication, likely due to poor polymerase recognition, dTPT3TPCF2 can, and moreover, its increased stability can contribute to increased UBP retention. The results demonstrate the promise of a chemical approach to SSO optimization.

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A semisynthetic organism engineered for the stable expansion of the genetic alphabet

Y. Zhang, B.M. Lamb, A.W. Feldman, A.X. Zhou, T. Lavergne, L. Li, F.E. Romesberg, Proc. Natl. Acad. Sci. USA (2017) 114: 1317–1322.
pubpic2017zhangWe describe an optimized SSO that is healthy, more autonomous than its predecessor, and able to store increased information indefinitely. The SSO constitutes a stable form of semisynthetic life and lays the foundation for efforts to impart life with new forms and functions. Read more in The Guardian, The Washington Post, TSRI News & Views, and The San Diego Union Tribune, or listen to an interview in This Way Up from Radio New Zealand.

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Transparent window vibrational probes for the characterization of proteins with high structural and temporal resolution

R. Adhikary, J. Zimmermann, F.E. Romesberg, Chem. Rev. (2017) 117:1927–1969.
pubpic2017adhikaryWe review the strengths and weaknesses of the different transparent window vibrational probes, methods by which they may be site-specifically incorporated into peptides and proteins, and the physicochemical properties they may be used to study. These topics are put into context through four case studies focused on KSI, SH3, DHFR, and cyt c.

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The expanding world of DNA and RNA

T. Chen, N. Hongdilokkul, Z. Liu, D. Thirunavukarasu, F.E. Romesberg, Curr. Op. Chem. Biol. (2016) 34:80–87.
pubpic2016bchenWe review nucleotide modifications, such as those to phosphate and sugar moieties that increase nuclease resistance or the range of activities possible, as well as whole nucleobase replacement that results in selective pairing and the creation of unnatural base pairs. Both in vitro and in vivo examples are discussed, including efforts to create semi-synthetic organisms with altered or expanded genetic alphabets.