20.500.12556/RUL-177231 Lipophilic cations as mitochondria-targeting moieties recent progress and design principles for medicinal chemistry Mitochondria-targeting technology, in the form of (lipophilic cation)–(small molecule) conjugates, was first discussed more than 50 years ago. Since then, the triphenylphosphonium (TPP) cation has become synonymous with the concept of a mitochondria-targeting moiety (MTM). The discovery of its ability to accumulate in mitochondria occurred alongside research on mitochondrial functions and the mechanisms underlying cation import. The recognition of intrinsic biological effects of TPP, apart from delivery of functional cargo, came much later, prompting the development of novel MTMs beyond the archetypal TPP. In this Perspective, we present the current understanding of the biological mechanisms of action of mitochondria-targeting conjugates, describe the methods used for their validation, and overview the recently developed novel mitochondria-targeting moieties. Building upon the recent advances, we propose a rational approach for the development of novel MTMs to be incorporated into the future MTM–linker–cargo therapeutics (MITACs, MITochondria-TArgeting Conjugates). assays cations conjugate acid-base pairs mitochondria sensor probes analize kationi konjugirani kislinsko-bazni par mitohondriji senzorske sonde farmacevtska kemija klinična kemija true false true Angleški jezik Slovenski jezik Članek v reviji 2025-12-18 08:47:02 2025-12-18 08:47:07 2025-12-29 03:54:04 0000-00-00 00:00:00 2025 0 0 Str. 23690−23704 iss. 22 Vol. 68 Nov. 2025 0000-00-00 Zaloznikova Objavljeno NiDoloceno 0000-00-00 0000-00-00 0000-00-00 543.2/.9 1520-4804 10.1021/acs.jmedchem.5c02076 261779971 lipophilic-cations-as-mitochondria-targeting-moieties-recent-progress-and-design-principles-for-medicinal-chemistry.pdf lipophilic-cations-as-mitochondria-targeting-moieties-recent-progress-and-design-principles-for-medicinal-chemistry.pdf 1 092830EF1E8EAB49D18D2499D87A6CFB f9b0fb2738d333642f7672d9157f0b28982299809a2c8127f6246f08cceb6dff 5e6a9dfa-dcde-11f0-9328-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=224254 https://pubs.acs.org/doi/10.1021/acs.jmedchem.5c02076 0 2551ed26-dbe6-11f0-9328-0050569b8976 https://repozitorij.uni-lj.si/Dokument.php?lang=slv&id=224149 Fakulteta za farmacijo 0 0 0