An overview of sulfur-containing compounds originating from natural metabolites: Lanthionine ketimine and its analogues

Shen, Dunxin; Hensley, Kenneth; Denton, Travis T.

doi:10.1016/j.ab.2019.113543

Cited by 5 publications

(4 citation statements)

References 90 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…Despite not knowing the exact mechanism of action, LK has been shown to significantly increase autophagy with possible downstream interactions with ULK1 or other proteins that regulate mTOR (instead of acting directly in mTOR), making it a novel candidate for a potential therapeutic 28 . LK is the cyclic ketenamine form of the mono-alpha-ketoacid form of lanthionine, which is typically produced by the transamination with the alpha-ketoacid form of methionine, alpha-keto-methylthiolbutyrate (αKMB), catalyzed by glutamine transaminase K 21 , 25 , 29 . Replacement of the 3-carboxylate with a phosphonate group and addition of alkyl groups to the 2-position of LK provide the lanthionine ketenamine (ester)-phosphonates (LK(E)-P 29 ).…”

Section: Discussionmentioning

confidence: 99%

“…Both LK and LKE slow down the decline of motor functions in a mouse model of amyotrophic lateral sclerosis 27 and activate autophagy in rat glioma and human neuroblastoma cells 28 . The need for new compounds to enhance autophagy and fight against neurodegenerative diseases has recently been addressed by the synthesis of new analogs of LK and LKE 25 , 29 . For instance, phosphonate analogs of LK (lanthionine ketenamine phosphonates (LK-Ps)) or LKE (lanthionine ketenamine (ester) phosphonates (LKE-Ps)) can enhance target engagement of LK 29 .…”

Section: Introductionmentioning

confidence: 99%

See 1 more Smart Citation

CTB-targeted protocells enhance ability of lanthionine ketenamine analogs to induce autophagy in motor neuron-like cells

Porras

Gransee

Denton

et al. 2023

Sci Rep

Self Cite

View full text Add to dashboard Cite

Impaired autophagy, a cellular digestion process that eliminates proteins and damaged organelles, has been implicated in neurodegenerative diseases, including motor neuron disorders. Motor neuron targeted upregulation of autophagy may serve as a promising therapeutic approach. Lanthionine ketenamine (LK), an amino acid metabolite found in mammalian brain tissue, activates autophagy in neuronal cell lines. We hypothesized that analogs of LK can be targeted to motor neurons using nanoparticles to improve autophagy flux. Using a mouse motor neuron-like hybrid cell line (NSC-34), we tested the effect of three different LK analogs on autophagy modulation, either alone or loaded in nanoparticles. For fluorescence visualization of autophagy flux, we used a mCherry-GFP-LC3 plasmid reporter. We also evaluated protein expression changes in LC3-II/LC3-I ratio obtained by western blot, as well as presence of autophagic vacuoles per cell obtained by electron microscopy. Delivering LK analogs with targeted nanoparticles significantly enhanced autophagy flux in differentiated motor neuron-like cells compared to LK analogs alone, suggesting the need of a delivery vehicle to enhance their efficacy. In conclusion, LK analogs loaded in nanoparticles targeting motor neurons constitute a promising treatment option to induce autophagy flux, which may serve to mitigate motor neuron degeneration/loss and preserve motor function in motor neuron disease.

show abstract

Section: Discussionmentioning

confidence: 99%

Section: Introductionmentioning

confidence: 99%

CTB-targeted protocells enhance ability of lanthionine ketenamine analogs to induce autophagy in motor neuron-like cells

Porras

Gransee

Denton

et al. 2023

Sci Rep

Self Cite

View full text Add to dashboard Cite

show abstract

“…Lanthionine ketenamine is a metabolite found in the mammalian brain and central nervous system. 6 Due to imine-enamine tautomerism, it is often described as either a ketimine or a ketenamine. Its biosynthetic pathway involves transamination of the nonproteinogenic amino acid lanthionine, followed by cyclic imine formation (Scheme 1a).…”

mentioning

confidence: 99%

Bioinspired peptide stapling generates stable enzyme inhibitors

Morewood

Nitsche

2022

Chem. Commun.

View full text Add to dashboard Cite

show abstract

“…Lanthionine ketenamine is a metabolite found in the mammalian brain and central nervous system. 8 Due to imineenamine tautomerism, it is often described as either a ketimine or a ketenamine. Its biosynthetic pathway involves transamination of the nonproteinogenic amino acid lanthionine, followed by cyclic imine formation (Scheme 1a).…”

mentioning

confidence: 99%