Axinellamines as broad-spectrum antibacterial agents: scalable synthesis and biology

R.A. Rodriguez, D.B. Steed, Y. Kawamata, S. Su, P.A. Smith, T.C. Steed, F.E. Romesberg, P.S. Baran, J. Am. Chem. Soc. (2014) 136:15403-15413.
pubpic2014rodriguezIn this collaborative work with the Baran Lab, we show that the axinellamines have promising activity against Gram-positive and Gram-negative bacteria, suggesting that their scaffold has the potential for further development. Details regarding their mode of action remain to be elucidated, but the axinellamines appear to cause secondary membrane destabilization and may inhibit normal septum formation..


Evidence of an unusual N-H—N hydrogen bond in proteins

R. Adhikary, J. Zimmermann, J. Liu, R. Forrest, T. Janicki, P. Dawson, S. Corcelli, F.E. Romesberg, J. Am. Chem. Soc. (2014) 136:13474-13477.
pubpic2014adhikaryWe characterize the IR stretching frequencies of deuterated variants of proline and four proline residues of an Src homology 3 domain protein. CD stretching frequencies are shifted to lower energies due to hyperconjugation with Ni electron density, and along with DFT calculations, the data reveal that the Ni+1-H–Ni interactions constitute H-bonds that may play an important role in protein folding, structure, and function.


A semi-synthetic organism with an expanded genetic alphabet

D.A. Malyshev, K. Dhami, T. Lavergne, T. Chen, N. Dai, J.M. Foster, I.R. Corrêa, F.E. Romesberg, Nature (2014) 509:385-388.
pubpic2014malyshevWe demonstrate that E. coli can stably maintain a plasmid containing d5SICS–dNaM with only the addition of an exogenously expressed algal nucleotide triphosphate transporter. Read the associated News & Views or read more in The New York Times, The Atlantic, Wired, Science, Chemistry World, and The San Diego Union Tribune. This work was also recognized as one of the top 10 scientific achievements of 2014 by Science.


IR probes of protein microenvironments: utility and potential for perturbation

R. Adhikary, J. Zimmermann, P.E. Dawson, F.E. Romesberg, ChemPhysChem (2014) 15:849-853.
pubpic2014adhikaryWe use IR spectroscopy to characterize nSH3 variants labeled with CN or N3 at five different positions. Like carbon-deuterium (C-D) bonds, CN and N3 can provide information about their surrounding protein environment, but unlike C-D, they tend to be perturbative and thus should be used with caution.


Natural-like replication of an unnatural base pair for the expansion of the genetic alphabet and biotechnology applications

L. Li, M. Degardin, T. Lavergne, D. Malyshev, K. Dhami, P. Ordoukhanian, F.E. Romesberg, J. Am. Chem. Soc. (2014) 136:826-829.
pubpic2013bliCover Story In this work, we identify dTPT3-dNaM, which is PCR amplified with a natural base pair-like efficiency and fidelity. We also show that the dTPT3 scaffold is uniquely tolerant of attaching a propargyl amine linker, enabling site-specific labeling of PCR-amplified DNA.