Rozners group in collaboration with Dharmacon, Vandebilt and Rochester researchers
recently reported in ACS Chemical Biology that replacement of a single phosphate linkage
between the first and second nucleosides of the passenger strand of a short interfering
RNA with an amide linkage almost completely abolished its undesired activity and restored
the desired activity of guide strands that had been compromised by unfavorable amide
modifications. Eliminating off-target activity of the passenger strand will be important
for improving therapeutic potential of short interfering RNAs.
Citation: Hardcastle, T., Novosjolova, I., Kotikam, V., Cheruiyot, S. K., Mutisya,
D., Kennedy, S. D., Egli, M., Kelley, M. L., Smith, Anja van B., and Rozners, E. A
Single Amide Linkage in the Passenger Strand Suppresses Its Activity and Enhances
Guide Strand Targeting of siRNAs. ACS Chem. Biol.2018, 13, 533-536.
Congratulations to Dan Ciulla (Callahan group) whose recent paper was featured on
the cover of the Journal of the American Chemical Society and featured in the journal's
Spotlight section. The paper describes a new approach to control the activity of a
cancer-related protein through the combined power of site-directed mutagenesis and
mechanism-guided chemical synthesis.
Citation: Ciulla, D.A,; Jorgensen, M.T.; Giner, J.L.; Callahan, B.P. Chemical Bypass
of General Base Catalysis in Hedgehog Protein Cholesterolysis Using a Hyper-Nucleophilic
Substrate. J Am Chem Soc.2018,140(3), 916-918.
The paper describes the identification of energetic contributions to the substrate
translocation by glutamate transporters and highlights the critical contribution of
charge compensation to transport, adding to results from previous molecular dynamics
simulations for improved understanding of the glutamate translocation process. This
work was funded by the NSF.
Citation: Wang J.; Albers†, T.; Grewer*, C. Energy Landscape of the Substrate Translocation
Equilibrium of Plasma-Membrane Glutamate Transporters. J. Phys. Chem. B,2018,122(1), 28–39
An article by Arvind Kumar, Shih-Sheng Sun and Alistair J. Lees published in Photophysics of Organometallics has been ranked 221 out of 64157 articles (published between 2010 to 2014) by Web
Citation: Kumar A.; Sun S.S.; Lees A.J. Photophysics and Photochemistry of Organometallic
Rhenium Diimine Complexes. In Photophysics of Organometallics, Lees A., Eds.; Topics in Organometallic Chemistry, Springer, Berlin, Heidelberg,
2009; vol 29.
Dr. Sozanne Solmaz, Assistant Professor, has published a paper in the Journal Cell
Cycle together with her students Kyle Loftus, Heying Cui, Amanda Ceravolo and Dylan
Perreiras, as well as collaborators David King and Elias Coutavas from UC Berkeley
and the Rockefeller University. The paper provides new insights how the transport
of the nucleus within the cell is initiated in G2 phase. Transport of the nucleus
is important for a fundamental process in brain development and faithful chromosome
segregation. Defects in these transport processes cause cancer and microcephaly, a
devastating brain developmental disease in infants. Results will help devise therapies
for these devastating diseases.
Citation: Loftus, K.M.; Cui, H.; Coutavas, E.; King, D.S.; Ceravolo, A.; Pereiras,
D.; Solmaz, S.R. Mechanism for G2 phase-specific nuclear export of the kinetochore
protein CENP-F. Cell Cycle, 2017,16, 1414-1429.
A recent paper in Nucleic Acids Research “Amide linkages mimic phosphates in RNA interactions
with proteins and are well tolerated in the guide strand of short interfering RNAs”
showcases results obtained by former graduate students Daniel Mutisya and Samwel Cheruiyot
in collaboration with several academic and industrial research groups
Citation: Mutisya, D.; Hardcastle, D.; Cheruiyot, S.; Pallan, P.; Kennedy, S.; Egli,
M.; Kelley, M.L.; van Brabant Smith, A.; Rozners, E. Amide linkages mimic phosphates
in RNA interactions with proteins and are well tolerated in the guide strand of short
interfering RNAs. Nucleic Acids Research,2017, 14, 8142-8155.
A recent paper in RNA journal "Sequence-selective recognition of double-stranded RNA
and enhanced cellular uptake of cationic nucleobase and backbone-modified peptide
nucleic acids” showcases results obtained by graduate student Dziyana Hnedzko and
undergraduate research assistant Yannis Karamitas in collaboration with Professor
Dennis McGee at the Biology Department.
Citation: Hnedzko, D.; McGee, D.W.; Karamitas, Y.A.; Rozners, E. Sequence-selective
recognition of double-stranded RNA and enhanced cellular uptake of cationic nucleobase
and backbone-modified peptide nucleic acids. RNA, 2017,23:, 58-69 .