Availability of basic tools for engineering molecular systems with precisely defined properties is crucial toward progress in development of new responsive materials. Among such materials are systems capable of generating an ultrasensitive response (i.e., large relative changes in output in response to small changes in input). Herein, we focus on a rational design of DNA quadruplex based structures as ultrasensitive response elements. In particular, we demonstrate how addition of allosteric guiding elements can be engineered into H(+)-responsive i-motif structure to yield maximized response sensitivity.