BEGIN:VCALENDAR VERSION:2.0 PRODID:-//jEvents 2.0 for Joomla//EN CALSCALE:GREGORIAN METHOD:PUBLISH BEGIN:VEVENT UID:83d91b649c839885ba08018630b096e7 CATEGORIES:Colloquium CREATED:20180329T144726 SUMMARY:Professor Hiroshi Sugiyama DESCRIPTION:
Hosted by Professor KiBum Lee
Tuesday September 4, 2 018
11:00AM, CCB* Auditorium
*New Che mistry and Chemical Biology Building
"Chemical Biology of Nucleic Acids: DNA Origami and Artificial Genetic Swit ch"
The DNA origami method developed for the preparation of fully add
ressable two-dimensional (2-D) structures has been utilized for the selecti
ve positioning of the functional molecules and nanoparticles. We desi
gned ”DNA frame” using the DNA origami method to investigate enzymatic acti
on and DNA structural change.[1] To observe the behaviors and re
actions of DNA methyltransferase and DNA repair enzymes, the substrate dsDN
As were incorporated into the cavity of the DNA frame, and the enzymes that
bound to the target dsDNA were observed using HS-AFM.[1] DNA re
combination was also observed using the recombination substrates and Hollid
ay junction intermediates placed in the DNA frame, and the direction of the
reactions was controlled by introducing structural stress to the substrate
s. To observe DNA structural changes such as G-quadruplex formation and dis
ruption, the switching behaviors of photoresponsive oligonucleotides, and B
?Z transition were visualized using the DNA frame observation system.
We recently developed DNA nanocages and investigated the effect of confine
d space on the property of G-quadruplex and found that mechanical and therm
odynamic stabilities of the G-quadruplex inside the nanocage are significan
tly increased.[2] Also a strategy for lipid-bilayer-assisted sel
f-assembly of various DNA origami tiles into 2-D lattices was developed.
We have been undertaking original research on the molecul ar recognition of DNA by antitumor antibiotics, and the analysis of atom-sp ecific chemical reaction on DNA. By reconstituting such knowledge, various functionalized sequence-specific DNA binding pyrrole-imidazole polyamides ( PIPs) were synthesized as an artificial genetic switch, which can switch on and switch off the gene expression on demand. We recently developed alkyla ting PIP that could switches off cancer related KRAS gene[4] and RUNX 1-3 controling genes.[5] To switch on the gene expression we need to consider Epigenetics. We developed a novel class of compound ter med, SAHA-PIP containing sequence-specific pyrrole-imidazole polyamides (PI Ps) and HDAC inhibiting SAHA. Evaluation of the effect of SAHA-PIPs on geno me-wide gene expression in human dermal fibroblasts (HDFs) divulged that ea ch SAHA-PIP could differentially activate the therapeutically important gen es.[6] Among them, the notable “ON” switching SAHA-PIPs in HDFs include ‘K’ for germ cell-associated PIWI pathway genes5 and ‘I’ for pluripotency-associated OCT4 pathway genes. Conjugation of DNA b inding domain of ‘I’ with HAT activating CTB remarkably activated identical cluster of genes as SAHA-PIP ‘I’ to substantiate the role of PIP in sequen ce-specific gene regulation.[7] In this talk recent progress of DNA origami technology and regulation of the gene expression using designed PIPs will be discussed.
Selected references:
1) Rajendran, A.; Endo, M.; Sugiyama, H. Chem. Rev. 2014, 114, 1493-1520.
2) Shresha, P.; Jonchhe, S.; Emura, T.et al. Nature Nanotech. 2017, 12, em> 582-588.
3) Suzuki, Y.; Endo, M.; Sugiyama, H. Nat Comm un., 2015, 6, 8052.€€”
4) Hiraoka, K.; Inoue, T.; Taylor, R. D. et al. Nature. Commun., 2015, 6, 6706.
5) Morita, K.; Suzuki, K.; Maeda, S. et al. J. Clin. Invest. 2017, 127, 2815-2828.
6) P
andian, G. N.; Taniguchi, J.; Junetha, S. et al. Sci. Rep., 2014, 4
7) Han, L.; Pandian, G, N.; Chandran, A.et al. < em>Angew. Chem. Int. Ed. 2015, 54, 8700-8703.
~Coffee/tea will be served prior to lecture.~
X-ALT-DESC;FMTTYPE=text/html:Hosted by Professor KiBum Lee
Tuesday September 4, 2018
11:00AM, CCB* Audito rium
*New Chemistry and Chemical Biology Building
&nbs p;
"Chemical Biology of Nucleic Acids: DNA Origami and Artificial Genetic Switch"
The DNA origami method developed for the preparation of fully addressable two-dimensional (2-D) structures has b een utilized for the selective positioning of the functional molecules and nanoparticles. We designed ”DNA frame” using the DNA origami method t o investigate enzymatic action and DNA structural change.[1] To observe the behaviors and reactions of DNA methyltransferase and DNA repair enzymes, the substrate dsDNAs were incorporated into the cavity of the DNA frame, and the enzymes that bound to the target dsDNA were observed using HS-AFM.[1] DNA recombination was also observed using the recombi nation substrates and Holliday junction intermediates placed in the DNA fra me, and the direction of the reactions was controlled by introducing struct ural stress to the substrates. To observe DNA structural changes such as G- quadruplex formation and disruption, the switching behaviors of photorespon sive oligonucleotides, and B?Z transition were visualized using the DNA fra me observation system. We recently developed DNA nanocages and invest igated the effect of confined space on the property of G-quadruplex and fou nd that mechanical and thermodynamic stabilities of the G-quadruplex inside the nanocage are significantly increased.[2] Also a strategy fo r lipid-bilayer-assisted self-assembly of various DNA origami tiles into 2- D lattices was developed.[3]
We have been undertaking orig inal research on the molecular recognition of DNA by antitumor antibiotics, and the analysis of atom-specific chemical reaction on DNA. By reconstitut ing such knowledge, various functionalized sequence-specific DNA binding py rrole-imidazole polyamides (PIPs) were synthesized as an artificial genetic switch, which can switch on and switch off the gene expression on demand. We recently developed alkylating PIP that could switches off cancer related KRAS gene[4] and RUNX 1-3 controling genes.[5] To sw itch on the gene expression we need to consider Epigenetics. We developed a novel class of compound termed, SAHA-PIP containing sequence-specific pyrr ole-imidazole polyamides (PIPs) and HDAC inhibiting SAHA. Evaluation of the effect of SAHA-PIPs on genome-wide gene expression in human dermal fibrobl asts (HDFs) divulged that each SAHA-PIP could differentially activate the t herapeutically important genes.[6] Among them, the notable “ON” switching SAHA-PIPs in HDFs include ‘K’ for germ cell-associated PIWI pathw ay genes5 and ‘I’ for pluripotency-associated OCT4 pathway genes . Conjugation of DNA binding domain of ‘I’ with HAT activating CTB re markably activated identical cluster of genes as SAHA-PIP ‘I’ to substantia te the role of PIP in sequence-specific gene regulation.[7] In t his talk recent progress of DNA origami technology and regulation of the ge ne expression using designed PIPs will be discussed.
Selected references:
1) Rajendran, A.; Endo, M.; Sugiyama, H. Chem. Rev. 2014, 114, 1493-1520.
2) Shresha, P.; Jonchhe, S.; Emura, T.et al. Nature Nanotech.
3) Suzuki, Y.; Endo, M .; Sugiyama, H. Nat Commun., 2015, 6, 80 52.€€”
4) Hiraoka, K.; Inoue, T.; Taylor, R. D. et al. Nature. Co mmun., 2015, 6, 6706.
5) Morita, K.; S uzuki, K.; Maeda, S. et al. J. Clin. Invest. 2017, 127 , 2815-2828.
6) Pandian, G. N.; Taniguchi, J.; Junetha, S. et al . Sci. Rep., 2014, 4, 3843.
7) Han, L.; Pandian, G , N.; Chandran, A.et al. Angew. Chem. Int. Ed. 2015, 54, 8700-8703.
~Coff ee/tea will be served prior to lecture.~
DTSTAMP:20240328T091811 DTSTART:20180904T150000 DTEND:20180904T160000 SEQUENCE:0 TRANSP:OPAQUE END:VEVENT END:VCALENDAR