Oral Presentation The 5th Prato Conference on Pore Forming Proteins 2021

Chemical translocation of biopolymers in a nanopore (#12)

Yujia Qing 1 , Hagan Bayley 1
  1. University of Oxford, OXFORD, OXON, United Kingdom

Ratcheting a single biopolymer strand through a nanoscopic detector for the sequential identification of its building blocks offers a universal means for single-molecule sequencing. This principle has been implemented in portable sequencers that use enzymes to ratchet DNA or RNA through hundreds of individual nanopore detectors positioned in an array. Nevertheless, its application to the sequencing of other biopolymers, including polypeptides and polysaccharides, has not progressed because suitable ratcheting enzymes are lacking. Recently, we devised a purely chemical means to translocate molecules in steps comparable to the repeat distances in biopolymers [1, 2]. With this chemical machine on a protein nanopore platform, we have further demonstrated sequential nucleobase identification during DNA translocation through a nanopore. Moreover, the modification of guanine with a chemotherapeutic platinum derivative is pinpointed with single-base resolution. Hence, chemical translocation has the potential to replace stepping by enzymes for highly parallel single-molecule biopolymer sequencing.

 

  1. Y. Qing, S. A. Ionescu, G. S. Pulcu, H. Bayley, Directional control of a processive molecular hopper. Science 361, 908–912 (2018).
  2. Y. Qing, H. Tamagaki-Asahina, S. A. Ionescu, M. D. Liu, H. Bayley, Catalytic site-selective substrate processing within a tubular nanoreactor. Nat. Nanotechnol. 14, 1135–1142 (2019).