PCR with an expanded genetic alphabet

D. Malyshev, Y.J. Seo, P. Ordoukhanian, F.E. Romesberg, J. Am. Chem. Soc. (2009) 131:14620-14621.
pubpic2009malyshevWe demonstrate that DNA containing either the d5SICS−dNaM or d55SICS−dMMO2 unnatural base pair may be amplified by PCR with fidelities and efficiencies that approach those of fully natural DNA.


 Major groove derivatization of an unnatural base pair

Y.J. Seo, F.E. Romesberg, ChemBioChem (2009) 10:2394-2400.
Cover Story We synthesize and evaluate several dMMO2 derivatives with meta-chlorine, -bromine, -iodine, -methyl, or -propinyl substituents. Complete characterization of unnatural base pair and mispair synthesis and extension reveal that the modifications have large effects only on the efficiency of unnatural base pair synthesis and that the effects likely result from a combination of changes in steric interactions, polarity, and polarizability.


The effects of unnatural base pairs and mispairs on DNA duplex stability and solvation

G.T. Hwang , Y. Hari, F.E. Romesberg, Nucleic Acids Res, (2009) 37:4757-4763.
pubpic2009hwangWeexamine six pyridine-based nucleotides, differentiated by methyl substitution, that are designed to vary both inter- and intra-strand packing within duplex DNA. We show that incorporation of one of these nucleobases, d34DMPy, as a self pair or as a mispair with dA significantly increases oligonucleotide hybridization fidelity at other positions within the duplex.


Efforts toward developing probes of protein dynamics: vibrational dephasing and relaxation of carbon-deuterium stretching modes in deuterated leucine

J. Zimmermann, K. Gundogdu, M.E. Cremeens, J.N. Bandaria, G.T. Hwang, M.C. Thielges, C.M. Cheatum, F.E. Romesberg, J. Phys. Chem. B (2009) 113:7991-7994.
pubpic2009bzimmermannWe present the first time-resolved experiments characterizing the population and dephasing dynamics of selectively excited C−D bonds in a deuterated amino acid using both three-pulse photon echo and transient grating experiments. We show that the steady-state C−D absorption linewidths in the deuterated amino acid are broadened by both homogeneous and inhomogeneous effects, and that IVR occurs on a subpicosecond time scale and is nonstatistical.


Synthesis and biological evaluation of penem inhibitors of bacterial signal peptidases

D.A. Harris, M.E. Powers, F.E. Romesberg, Bioorg. Med. Chem. Lett. (2009) 19:3787-3790.
pubpic2009harrisWe report the first synthesis of a 5S penem, known to bind bacterial type I signal peptidase, from the commercially available and inexpensive 6-aminopenicillanic acid, and we use structure–activity relationship studies to begin to define the determinants of signal peptidase binding and to optimize the penem as an antibiotic.


Direct observation of structural heterogeneity in a β-sheet

M.E. Cremeens, J. Zimmermann, W. Yu, P.E. Dawson, F.E. Romesberg, J. Am. Chem. Soc. (2009) 131:5726-5727.
pubpic2009cremeensWe demonstrate that deuterium atoms incorporated at Cα backbone positions (Cα−D bonds) are sensitive to the local backbone structure. DFT calculations are used to predict that Cα−D bonds of glycine are sensitive to their local structure, with the absorptions red-shifted for an extended β-sheet relative to γ- and α-helix-like turns. These predictions are confirmed in glycine-deuterated variants of the N-terminal Src homology 3 (nSH3) domain protein.