Lipophilic cations as mitochondria-targeting moieties : recent progress and design principles for medicinal chemistry

Džajić, Ivan (avtor), Tomašič, Tihomir (avtor), Pardo A., Luis (avtor), Peterlin-Mašič, Lucija (avtor), Cotman, Andrej Emanuel (avtor)

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).

• Jezik: Angleški jezik
• Ključne besede: assays, cations, conjugate acid-base pairs, mitochondria, sensor probes
• Vrsta gradiva: Članek v reviji
• Tipologija: 1.02 - Pregledni znanstveni članek
• Organizacija: FFA - Fakulteta za farmacijo
• Status publikacije: Objavljeno
• Različica publikacije: Objavljena publikacija
• Leto izida: 2025
• Št. strani: Str. 23690−23704
• Številčenje: Vol. 68, iss. 22
• PID: 20.500.12556/RUL-177231
• UDK: 543.2/.9
• ISSN pri članku: 1520-4804
• DOI: 10.1021/acs.jmedchem.5c02076
• COBISS.SI-ID: 261779971
• Datum objave v RUL: 18.12.2025

Gradivo je del revije

• Naslov: Journal of medicinal chemistry
• Skrajšan naslov: J. med. chem.
• Založnik: American Chemical Society
• ISSN: 1520-4804
• COBISS.SI-ID: 512806681

Licence

• Licenca: CC BY 4.0, Creative Commons Priznanje avtorstva 4.0 Mednarodna
• Povezava: http://creativecommons.org/licenses/by/4.0/deed.sl
• Opis: To je standardna licenca Creative Commons, ki daje uporabnikom največ možnosti za nadaljnjo uporabo dela, pri čemer morajo navesti avtorja.

Sekundarni jezik

• Jezik: Slovenski jezik
• Ključne besede: analize, kationi, konjugirani kislinsko-bazni par, mitohondriji, senzorske sonde, farmacevtska kemija, klinična kemija