Identification of the first enantiopure Rac1–Tiam1 protein–protein interaction inhibitor and its optimized synthesis <i>via</i> phosphine free remote group directed hydroarylation

Ruffoni, Alessandro; Ferri, Nicola; Pinto, Andrea; Pellegrino, Sara; Contini, Alessandro; Clerici, Francesca

doi:10.1039/c8md00477c

Cited by 4 publications

(2 citation statements)

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“…There are several Rac1-Tiam1 (GEF) (T-cell lymphoma invasion and metastasis 1) inhibitors. 254 − 257 The structural studies identified the specific amino acid residues. 253 In addition to small molecule inhibitors, there were attempts to develop peptide-derived Rac1-Tiam1 inhibitors.…”

Section: Strategies Toward Regulation Of Activity Of Small Gtpases Via Their Direct Targeting or Inhibition Of Mevalonate Pathway Enzymesmentioning

confidence: 99%

“…As has been already mentioned, one of the most popular strategies to inhibit Rac1 activation is the interruption of its binding with GEFs. There are several Rac1-Tiam1 (GEF) (T-cell lymphoma invasion and metastasis 1) inhibitors. − The structural studies identified the specific amino acid residues . In addition to small molecule inhibitors, there were attempts to develop peptide-derived Rac1-Tiam1 inhibitors …”

Section: Strategies Toward Regulation Of Activity Of Small Gtpases Vi...mentioning

confidence: 99%

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Targeting Small GTPases and Their Prenylation in Diabetes Mellitus

2021

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A fundamental role of pancreatic β-cells to maintain proper blood glucose level is controlled by the Ras superfamily of small GTPases that undergo post-translational modifications, including prenylation. This covalent attachment with either a farnesyl or a geranylgeranyl group controls their localization, activity, and protein–protein interactions. Small GTPases are critical in maintaining glucose homeostasis acting in the pancreas and metabolically active tissues such as skeletal muscles, liver, or adipocytes. Hyperglycemia-induced upregulation of small GTPases suggests that inhibition of these pathways deserves to be considered as a potential therapeutic approach in treating T2D. This Perspective presents how inhibition of various points in the mevalonate pathway might affect protein prenylation and functioning of diabetes-affected tissues and contribute to chronic inflammation involved in diabetes mellitus (T2D) development. We also demonstrate the currently available molecular tools to decipher the mechanisms linking the mevalonate pathway’s enzymes and GTPases with diabetes.

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Section: Strategies Toward Regulation Of Activity Of Small Gtpases Via Their Direct Targeting or Inhibition Of Mevalonate Pathway Enzymesmentioning

confidence: 99%