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The stapled peptide they used involved olefinic amino acid Fmoc-( S )-2-(4entenyl)-alanine bound at suitable i , i + 4 positions at the non-binding interface as the staple, and it was found that both selected stapling peptides LCIP1 and LRIP4 exhibited improved cell permeability as compared to the native one in a dose-dependent manner monitored by flow cytometry [130]

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Abbreviations RA: Rheumatoid arthritis mTOR: Mechanistic target of rapamycin raptor: Regulatory-associated protein of TOR mlst8: Mammalian lethal with sec-13 protein 8 deptor: DEP domaincontaining mTOR interacting protein pras40: Proline-rich Akt substrate of 40kD rictor: Rapamycin-insensitive companion of mTOR msin1: Stress-activated protein kinase interacting protein 1 PI3K: Phosphatidylinositol-3-OH kinase AKT: RAC- serine/threonine-protein kinase TSC: Threonine-protein kinase/tuberous sclerosis complex LKB1: Liver kinase B1 AMPK: Mitogen-activated protein kinase TLR: Toll-like receptor Rheb: Ras homolog enriched in the brain PTEN: Phosphatase and tensin homolog deleted on chromosome 10 PIP2: Ephosphatidylinositol-3,4-bisphosphate PIP3: Phosphatidylinositol-3,4,5-triphosphate S6K1: S6 kinase 1 eIF4E: Eukaryotic translation initiation factor 4E eIF4B: Eukaryotic translation initiation factor 4B 4E-BP1: EIF4E binding protein 1 PDCD4: Programmed cell death protein 4 SKAR: S6K1 Aly/REF-like target ATF4: Activating transcription factor 4 MTHFD2: Methylenetetrahydrofolate dehydrogenase 2 CAD: Carbamoyl-phosphate synthetase HIF1: Hypoxia-inducible factor-1 ULK1: Unc-51-like kinase1 TFEB: Transcription factor EB SGK1: Serum and glucocorticoid inducible kinase 1 PKC: Protein kinase C- FLSs: Fibroblast-like synoviocytes Teffs: Effector T cells Tregs: Regulatory T cells MLS: Macrophage-like synoviocytes SMs: Synovial macrophages OC: Osteoclast TGF-: Factor- DC: Dendritic cell Flt3L: Flt3 ligand NAC: N-acetylcysteine NF-B: Nuclear factor B ROS: Reactive oxygen species Met: Metformin References McInnes IB, Schett G