Rational design of tunable pH switches through shadow-strand hybridization-actuated displacement engineering.

ABSTRACT: Local pH variations play a pivotal role in numerous critical biological processes. However, achieving the tunability and selectivity of pH detection remains a challenge. Here, we present a DNA-based strategy that enables programmable and selective pH responses, which is termed shadow-strand hybridization-actuated displacement engineering (SHADE). The tunability of pH responses is accomplished via rational manipulations of shadow strands derived from the i-motif-forming sequence. Shadow strands, which can be considered the "nucleic acid molecular chaperones," assist in the folding of i-motif structure under acidic conditions via toehold-mediated strand displacement reactions (TMSDR). The response to alkaline conditions is achieved through a hairpin shadow (HS) containing A+-C pairs in stem.

SUBMITTER: Han X 

PROVIDER: S-EPMC12412784 | biostudies-literature | 2025 Sep

REPOSITORIES: biostudies-literature