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PIP–NaCo, a Synergic DNA Binding System Assisted by Orthogonal γPNA Dimerization Domains with Cooperativity and Versatility

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Part of the Springer Theses book series (Springer Theses)

Abstract

Synthetic molecules capable of DNA binding and mimicking cooperation of transcription factor (TF) pairs have long been considered as a promising tool for manipulating gene expression. Our previous 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 due to its bioorthogonality, sequence specific interaction, and high binding affinity toward the partner strand. The cooperativity is highly comparable with 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 reasonably. Current PIP–NaCo platform might also have the potential for precise manipulation of biological processes through the constitution of triple to multiple hetero binding systems.

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© Springer Nature Singapore Pte Ltd. 2020

Authors and Affiliations

  1. 1.Department of Chemistry, Graduate School of ScienceKyoto UniversityKyotoJapan

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