Structural insights into DNA replication without hydrogen bonds

K. Betz, D.A. Malyshev, T. Lavergne, W. Welte, K. Diederichs, F.E. Romesberg, A. Marx, J. Am. Chem. Soc. (2013) 135:18637-18643.
pubpic2013betzWe report the structural characterization of the prechemistry complexes with KlenTaq polymerase corresponding to the insertion of dNaMTP opposite d5SICS, as well as mulitple postchemistry complexes in which the already formed unnatural base pair is positioned at the postinsertion site.


Efforts toward broadening the spectrum of arylomycin antibiotic activity

J. Liu, P.A. Smith, D.B. Steed, F.E. Romesberg, Bioorg. Med. Chem. Lett., (2013) 23:5654-5659.
pubpic201liuWe report the synthesis and evaluation of several arylomycin derivatives, and demonstrate that both C-terminal homologation with a glycyl aldehyde and addition of a positive charge to the macrocycle increase the activity and spectrum of the arylomycin scaffold.


Chapter 776 – SpsB Signal Peptidases

D.A. Harris, F.E. Romesberg, Handbook of Proteolytic Enzymes (Third Edition)., N.D. Rawlings, G. Salvesen, Eds. (2013) Volume 3, 3501-3508.
pubpic2013harrisWe provide a concise review of type I signal peptidases, including historical and structural biology information, as well as preparation methods and work to identify inhibitors.


Site-specifically arraying small molecules or proteins on DNA using an expanded genetic alphabet

Z. Li, T. Lavergne, D.A. Malyshev, J. Zimmermann, R. Adhikary, K. Dhami, P. Ordoukhanian, Z. Sun, J. Xiang, F.E. Romesberg, Chem. Eur. J. (2013) 19:14205-14209.
pubpic2013liWe report the synthesis and characterization of unnatural base pairs bearing propynyl groups, and their use to site-specifically label amplified DNA via Click chemistry. We demonstrate the attachment of a small molecule biotin tag, and for the first time a protein (SH3), to a large, PCR amplified fragment of DNA, as well as the arraying of two proteins on the same duplex.


Experimental characterization of electrostatic and conformational heterogeneity in an SH3 domain

R. Adhikary, J. Zimmermann, J. Liu, P.E. Dawson, F.E. Romesberg, J. Phys. Chem. B, 117:13082-13089.
pubpic2013adhikaryWe use the IR absorptions of carbon-deuterium bonds site-selectively incorporated throughout the N-terminal SH3 domain from the murine adapter protein CrkII to characterize its different microenvironments with high spatial and temporal resolution.


Expanding the scope of replicable unnatural DNA: Stepwise optimization of a predominantly hydrophobic base pair

T. Lavergne, M. Degardin, D.A. Malyshev, H.T. Quach, K. Dhami, P. Ordoukhanian, F.E. Romesberg, J. Am. Chem. Soc. (2013) 135:5408-5419.
pubpic2013lavergneWe report the stepwise optimization of dMMO2 via the synthesis and evaluation of eighteen novel para-derivatized analogs of dMMO2, followed by further derivatization and evaluation of the most promising analogs with meta substituents. The most promising, d5SICS-dFEMO, is replicated under some conditions with greater efficiency and fidelity than d5SICS-dNaM.