Spring 2012 Biomedical Seminar Series
Friday, April 20, 2012
Abstract Quinoxaline incorporated cavitands are used as intermediates for the synthesis of various host-guest molecules. , Quinoxaline moieties as protecting groups have yielded excellent results in our laboratory. In 2006, Tunstad et al. published new capsules of quinoxaline-spanned cavitands that showed great potential, but were unable to bind guest molecules due to excessive flexibility. Herein we report progress towards a new generation of interdigitated quinoxaline-spanned cavitand capsules whose righty may enhance binding and selectivity. The synthetic progress towards the new quinoxaline capsules will be presented. References (1) Castro, P. P.; Zhao, G.; Masangkay, G. A.; Hernandez, C.; Gutierrez-Tunstad, L. M. Org. Lett. 2004, 6, 3, pp 333-336. (2) Pochorovski, Igor; Diederich, FranÃ§ois Isr. J. Chem. 2001, Online Early View. (3) Osuna, J. ÂSynthesis of Elaborate Quinoxaline CavitandsÂ Undergraduate MARC Honors Thesis, California State University, Los Angeles, CA, 2007. Private publication. Kang S., Castro P. P., Zhao G., Nunez J. E., Godinez, C. E., Gutierrez-Tunstad L. M. J. Org. Chem. 2006, 71, pp 1240-1243.
Abstract Wdr68 is a 343 amino acid WD40-repeat domain containing protein required for craniofacial development in the zebrafish Danio rerio. Though WD40-repeat domains are well characterized for their role in mediating protein-protein interactions, the detailed mechanism for Wdr68 function is not well understood. The Wdr68 protein physically interacts with two members of the Dual-specificity tyrosine-regulated kinase (Dyrk) family, Dyrk1a and Dyrk1b. Both Dyrk1a and Dyrk1b possess Nuclear Localization Signals (NLSs) and the subcellular localization of Wdr68 mirrors that of its interaction partners. Consistent with a functional requirement in the nucleus, a derivative of Wdr68 that is unable to localize to the nucleus is also incapable of supporting craniofacial development. Wdr68 and Dyrk1b are important for the expression of several signaling molecules involved in craniofacial development and Dyrk1b can inhibit the function of a transcriptional co-repressor, HDAC5. Consistent with a direct role in the regulation of gene expression, it was previously found that while a fusion between the Cebp1 transcriptional activation domain and Wdr68 can restore jaw cartilages in wdr68 knockdown a zebrafish RNA rescue assay in vivo, a fusion between the Mad1 repression domain and Wdr68 failed to rescue. Taken together, these findings suggest a nuclear Dyrk1b-Wdr68 complex with transcriptional co-activating functions. A series of Wdr68 deletions that fail to interact with Dyrk1a were recently reported. Concurrently, I constructed two Wdr68 deletions that remove sequences outside the WD40-repeats, 19C lacks amino acids at the N-terminus (1-18), and N336 lacks amino acids at the C-terminus (337-343). While located outside the WD40-repeats, these regions are among the most conserved in Wdr68. Because we expect that physical interaction with Dyrk1 family members is required for Wdr68 function, it was hypothesized that both N and C termini are required for Wdr68 function in Zebrafish craniofacial development.
Inadvertent introduction of microorganisms originating from earth to an extraterrestrial surface could compromise scientific integrity of future life-detection missions. Accordingly, current planetary protection protocols require that spacecraft be assembled and readied for launch in controlled clean rooms. Though the extreme conditions of spacecraft assembly clean rooms are effective in reducing the overall microbial load, they favor for the selective proliferation of Âphysiologically recalcitrantÂ microorganisms capable of tolerating desiccation, dry heat and radiation. These hardy microorganisms may survive the 'dry heat treatment' aimed for sterilization of spacecraft components. It was reported earlier that dry heat resistance of indigenous soil flora is much higher than the pure cultures isolated from the same soil. In an attempt to compare this difference in dry heat resistance, a bacterial strain was isolated from soil samples outside Kennedy Space Center, Florida. Soil samples were exposed to 125oC for 48 h before the isolation. The isolated bacterial strain (ATCC27380T) was subjected biochemical characterization, fatty acid analysis. Strain ATCC27380T showed optimum growth at 20?C, a pH range of 6.0-10.0 and was able to grow in NaCl concentration of 0-2% (W/V). The novel strain has colony morphology of dry, 2mm in diameter, cream colored, non-elevated colonies with smooth edges when grown on R2A medium for 48h. The predominant fatty acids found in this strain were 15:0 anteiso, 15:0 iso and 14:0 iso. This isolate was earlier reported to exhibit extreme resistance to dry heat (150Â°C) with D-values of 2.5 h. Based on results thus far, it appears that this isolate belongs to genus Paenibacillus and represents a novel species. The authors of this study propose the name Paenibacillus xerothermodurans sp. nov. ATCC27380T after its capability to resist extreme dry heat conditions.