Exploiting Chaotropic Salt-Nucleic Acid Interactions for Biotechnology and Understanding the Origins of Life

Abstract

The dynamic nature of nucleic acid structures is pivotal for dictating function and maintaining homeostasis, with environmental factors playing a significant role in controlling conformational integrity. Ions are a valuable means of assessing structural stability due to their dual mode of action: modulating water activity and directly interacting with biopolymers. In this dissertation, the strong chaotropic anion perchlorate emphasized a significant stability difference between the G-quadruplex secondary structure and the canonical double helix. This allowed for the rational design of extremely salt-resistant DNA-based biosensors tunable via concentration or dilution. The structural stability of nucleic acid polymers is also recognized through the endurance of ribozymes to maintain activity in chaotropic extraterrestrial brines, such as those found on Mars, supporting the idea that RNA can bridge the gap between prebiotic chemistry and cellular life. Together, this body of work contributes to the fundamental understanding of biomolecular stability in the context of both past and present life and the practical utility of understanding the underlying mechanisms.