FRINK Linked Data Fragments server

Matches in SemOpenAlex for { <https://semopenalex.org/work/W2968753885> ?p ?o ?g. }

• W2968753885 abstract "Abstract Mitochondrial dysfunction includes heritable diseases, acquired pathologies, and age-related declines in health. Szeto-Schiller (SS) peptides comprise a class of amphipathic tetrapeptides that have demonstrated efficacy in treating a wide array of mitochondrial disorders, and are believed to target mitochondrial membranes due to their enrichment in the anionic phospholipid cardiolipin (CL). However, little is known regarding how SS peptides interact with or alter the physical properties of lipid bilayers. In this study, we have analyzed the interactions of the lead compound SS-31 (Elamipretide) with model and mitochondrial membranes using biophysical and computational approaches. Our results show that this polybasic peptide partitions into the membrane interfacial region with affinity and binding density that are directly related to surface charge. SS-31 binding does not destabilize lamellar bilayers even at the highest binding concentrations; however, it does cause saturable alterations in lipid packing. Most notably, SS-31 modulates the surface electrostatic properties of model and mitochondrial membranes, which could play a significant role in the mitoprotective properties of this compound. As a proof of concept, we show that SS-31 alters ion distribution at the membrane interface with implications for maintaining mitochondrial membranes subject to divalent cation (calcium) stress. Taken together, these results support a mechanism of action in which SS peptides interact with lipid bilayers and alter the biophysical (primarily electrostatic) properties of mitochondrial membranes as their primary mechanism of action. Understanding this molecular mechanism is key to the development of future compound variants with enhanced efficacy. Significance Szeto-Schiller (SS) peptides are among the most promising therapeutic compounds for mitochondrial dysfunction. However, the molecular target(s) and the mechanism of action of SS peptides are poorly understood. In this study, we evaluate the interaction of the lead compound SS-31 (Elamipretide) with mitochondrial and synthetic model membranes using a host of biophysical techniques. Our results show that SS-31 membrane interaction is driven largely by the negative surface charge of mitochondrial membranes and that SS-31 alters lipid bilayer properties, most notably electrostatics at the membrane interface. This work supports a mechanism in which SS peptides act on a key physical property of mitochondrial membranes rather than with a specific protein complex, consistent with the exceptionally broad therapeutic efficacy of these compounds." @default.
• W2968753885 created "2019-08-22" @default.
• W2968753885 creator A5007254483 @default.
• W2968753885 creator A5015804781 @default.
• W2968753885 creator A5024057589 @default.
• W2968753885 creator A5024516638 @default.
• W2968753885 creator A5027294479 @default.
• W2968753885 creator A5039847629 @default.
• W2968753885 creator A5043666887 @default.
• W2968753885 creator A5045288576 @default.
• W2968753885 creator A5046512580 @default.
• W2968753885 creator A5052503675 @default.
• W2968753885 creator A5079050868 @default.
• W2968753885 creator A5087249159 @default.
• W2968753885 date "2019-08-14" @default.
• W2968753885 modified "2023-10-17" @default.
• W2968753885 title "Molecular Mechanism of Action of Mitochondrial Therapeutic SS-31 (Elamipretide): Membrane Interactions and Effects on Surface Electrostatics" @default.
• W2968753885 cites W122746954 @default.
• W2968753885 cites W130559879 @default.
• W2968753885 cites W1555206873 @default.
• W2968753885 cites W1722845210 @default.
• W2968753885 cites W1958746655 @default.
• W2968753885 cites W1969990769 @default.
• W2968753885 cites W1970577924 @default.
• W2968753885 cites W1971760965 @default.
• W2968753885 cites W1974771116 @default.
• W2968753885 cites W1978747518 @default.
• W2968753885 cites W1979161424 @default.
• W2968753885 cites W1979354689 @default.
• W2968753885 cites W1982313038 @default.
• W2968753885 cites W1990269392 @default.
• W2968753885 cites W2000742321 @default.
• W2968753885 cites W2002900567 @default.
• W2968753885 cites W2012181342 @default.
• W2968753885 cites W2012657176 @default.
• W2968753885 cites W2016528090 @default.
• W2968753885 cites W2032478715 @default.
• W2968753885 cites W2046189032 @default.
• W2968753885 cites W2048654159 @default.
• W2968753885 cites W2051022520 @default.
• W2968753885 cites W2053253687 @default.
• W2968753885 cites W2054739775 @default.
• W2968753885 cites W2055456981 @default.
• W2968753885 cites W2059053859 @default.
• W2968753885 cites W2068419531 @default.
• W2968753885 cites W2073016298 @default.
• W2968753885 cites W2082047232 @default.
• W2968753885 cites W2083822522 @default.
• W2968753885 cites W2100271206 @default.
• W2968753885 cites W2117911689 @default.
• W2968753885 cites W2118282477 @default.
• W2968753885 cites W2127184963 @default.
• W2968753885 cites W2131415852 @default.
• W2968753885 cites W2140168102 @default.
• W2968753885 cites W2156478040 @default.
• W2968753885 cites W2161080023 @default.
• W2968753885 cites W2169908718 @default.
• W2968753885 cites W2412195345 @default.
• W2968753885 cites W2473281433 @default.
• W2968753885 cites W2513964174 @default.
• W2968753885 cites W2557292438 @default.
• W2968753885 cites W2568720009 @default.
• W2968753885 cites W2586204880 @default.
• W2968753885 cites W2601743360 @default.
• W2968753885 cites W2612876306 @default.
• W2968753885 cites W2618607290 @default.
• W2968753885 cites W2671326645 @default.
• W2968753885 cites W2745530328 @default.
• W2968753885 cites W2788314593 @default.
• W2968753885 cites W2789236231 @default.
• W2968753885 cites W2802682760 @default.
• W2968753885 cites W2896859098 @default.
• W2968753885 cites W2898707230 @default.
• W2968753885 cites W2907561736 @default.
• W2968753885 cites W4210476933 @default.
• W2968753885 cites W605580770 @default.
• W2968753885 cites W75797419 @default.
• W2968753885 cites W2322059529 @default.
• W2968753885 doi "https://doi.org/10.1101/735001" @default.
• W2968753885 hasPublicationYear "2019" @default.
• W2968753885 type Work @default.
• W2968753885 sameAs 2968753885 @default.
• W2968753885 citedByCount "3" @default.
• W2968753885 countsByYear W29687538852020 @default.
• W2968753885 crossrefType "posted-content" @default.
• W2968753885 hasAuthorship W2968753885A5007254483 @default.
• W2968753885 hasAuthorship W2968753885A5015804781 @default.
• W2968753885 hasAuthorship W2968753885A5024057589 @default.
• W2968753885 hasAuthorship W2968753885A5024516638 @default.
• W2968753885 hasAuthorship W2968753885A5027294479 @default.
• W2968753885 hasAuthorship W2968753885A5039847629 @default.
• W2968753885 hasAuthorship W2968753885A5043666887 @default.
• W2968753885 hasAuthorship W2968753885A5045288576 @default.
• W2968753885 hasAuthorship W2968753885A5046512580 @default.
• W2968753885 hasAuthorship W2968753885A5052503675 @default.
• W2968753885 hasAuthorship W2968753885A5079050868 @default.
• W2968753885 hasAuthorship W2968753885A5087249159 @default.
• W2968753885 hasBestOaLocation W29687538851 @default.
• W2968753885 hasConcept C12554922 @default.
• W2968753885 hasConcept C178790620 @default.

• next