Orthogonal γPNA Dimerization Domains Empower DNA Binders with Cooperativity and Versatility Mimicking that of Transcription Factor Pairs

Chemistry : a European Journal
Zutao YuHiroshi Sugiyama

Abstract

Synthetic molecules capable of DNA binding and mimicking cooperation of transcription factor (TF) pairs have long been considered a promising tool for manipulating gene expression. Our previously reported Pip-HoGu system, a programmable DNA binder pyrrole-imidazole polyamides (PIPs) conjugated to host-guest moiety, defined a general framework for mimicking cooperative TF pair-DNA interactions. Here, we supplanted the cooperation modules with left-handed (LH) γPNA modules: i.e., PIPs conjugated with nucleic acid-based cooperation system (Pip-NaCo). LH γPNA was chosen because of its bioorthogonality, sequence-specific interaction, and high binding affinity toward the partner strand. From the results of the Pip-NaCo system, cooperativity is highly comparable to the natural TF pair-DNA system, with a minimum energetics of cooperation of -3.27 kcal mol-1 . Moreover, through changing the linker conjugation site, binding mode, and the length of γPNAs sequence, the cooperative energetics of Pip-NaCo can be tuned independently and rationally. The current Pip-NaCo platform might also have the potential for precise manipulation of biological processes through the construction of triple to multiple heterobinding systems.

References

Feb 15, 1993·Proceedings of the National Academy of Sciences of the United States of America·M D Distefano, P B Dervan
May 8, 1997·Nature·J M GottesfeldP B Dervan
Aug 3, 2006·Journal of the American Chemical Society·Anca Dragulescu-AndrasiDanith H Ly
Nov 18, 2006·Angewandte Chemie·Juan B BlancoJosé L Mascareñas
Mar 21, 2008·Physical Review. E, Statistical, Nonlinear, and Soft Matter Physics·Umesh KadhaneSteen Brøndsted Nielsen
Apr 22, 2008·ACS Chemical Biology·Rocco MorettiAseem Z Ansari
Jan 25, 2011·Nature Chemistry·David Yu Zhang, Georg Seelig
Aug 2, 2011·Chembiochem : a European Journal of Chemical Biology·Elena PazosJosé L Mascareñas
Feb 22, 2012·Nucleic Acids Research·Calista K L NgRalf Jauch
Jan 22, 2013·Cell·Arttu JolmaJussi Taipale
Nov 22, 2014·Nucleic Acids Research·Nate P HoverterMarian L Waterman
Jun 17, 2015·Journal of the American Chemical Society·Iulia SacuiDanith H Ly
Sep 1, 2015·The Journal of Organic Chemistry·Satheesh Ellipilli, Krishna N Ganesh
Jun 2, 2016·International Journal of Molecular Sciences·Maolin WangGe Zhang
Aug 4, 2016·Biopolymers·Or Berger, Ehud Gazit
Aug 17, 2016·Cancers·Aditi J Ravindranath, Ken M Cadigan
Mar 30, 2017·Current Opinion in Structural Biology·Ekaterina Morgunova, Jussi Taipale
Jul 8, 2017·European Journal of Medicinal Chemistry·Zutao YuHiroshi Sugiyama
Nov 28, 2017·Bioconjugate Chemistry·Dalu ChangNicolas Winssinger
Feb 3, 2018·Journal of the American Chemical Society·Zutao YuHiroshi Sugiyama
May 27, 2015·Tetrahedron·Arunava MannaDanith H Ly

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Citations

Dec 18, 2020·Chemical Record : an Official Publication of the Chemical Society of Japan ... [et Al.]·Takuya Hidaka, Hiroshi Sugiyama
Feb 12, 2019·Advanced Drug Delivery Reviews·Zutao YuHiroshi Sugiyama

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