Mukherjee Sanjib K, Singh Himanshu
Department of Chemistry, SRM IST Delhi-NCR Campus Delhi Modinagar, Uttar Pradesh 201204, India.
Department of Biosciences and Bioengineering, Indian Institute of Technology Guwahati, Guwahati, Assam 781039, India.
J Phys Chem Lett. 2025 Aug 14;16(32):8363-8368. doi: 10.1021/acs.jpclett.5c01547. Epub 2025 Aug 7.
Noncanonical nucleic acid conformations like G-quadruplexes and i-motifs are key regulators of gene function, genome stability, and drug action. Their structural dynamics in extreme conditions of high pressure and molecular crowding are therefore necessary to determine for a clear understanding of their biological role. Single-molecule Förster resonance energy transfer (sm-FRET) has proven to be an invaluable tool to examine these dynamic structures at heterogeneous environments. In this review, we discuss recent advancements in single molecule studies that investigate the impact of high pressure and crowding on noncanonical nucleic acids. We examine how these conditions influence the structural stability, folding kinetics, and conformational transitions, shedding light on their behavior in the crowded and heterogeneous intracellular environment. Through integration of existing knowledge, we provide insights into the broader implications of noncanonical nucleic acid structures in biological systems and their potential applications in biotechnology and medicine. This review underscores the necessity of studying nucleic acids beyond standard conditions to better grasp their functional relevance
非经典核酸构象，如G-四链体和i-基序，是基因功能、基因组稳定性和药物作用的关键调节因子。因此，为了清楚地了解它们的生物学作用，有必要确定它们在高压和分子拥挤的极端条件下的结构动力学。单分子荧光共振能量转移（sm-FRET）已被证明是在异质环境中研究这些动态结构的宝贵工具。在这篇综述中，我们讨论了单分子研究的最新进展，这些研究调查了高压和拥挤对非经典核酸的影响。我们研究了这些条件如何影响结构稳定性、折叠动力学和构象转变，揭示了它们在拥挤和异质细胞内环境中的行为。通过整合现有知识，我们深入了解了非经典核酸结构在生物系统中的更广泛意义及其在生物技术和医学中的潜在应用。这篇综述强调了在标准条件之外研究核酸以更好地理解其功能相关性的必要性。
