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Chemical Structure| 209627-36-1 Chemical Structure| 209627-36-1

Structure of 209627-36-1

Chemical Structure| 209627-36-1

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Morstein, Johannes ; Shrestha, Rebika ; Van, Que N. ; Lopez, Cesar A. ; Arora, Neha ; Tonelli, Marco , et al.

Abstract: Protein-membrane interactions (PMIs) are ubiquitous in cellular signaling. Initial steps of signal transduction cascades often rely on transient and dynamic interactions with the inner plasma membrane leaflet to populate and regulate signaling hotspots. Methods to target and modulate these interactions could yield attractive tool compounds and drug candidates. Here, the conjugation of a medium-chain lipid tail to the covalent K-Ras(G12C) binder MRTX849 at a solvent-exposed site enables such direct modulation of PMIs. The conjugated lipid tail interacts with the tethered membrane and changes the relative membrane orientation and conformation of K-Ras(G12C), as shown by mol. dynamics (MD) simulation-supported NMR studies. In cells, this PMI modulation restricts the lateral mobility of K-Ras(G12C) and disrupts nanoclusters. The described strategy could be broadly applicable to selectively modulate transient PMIs.

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Product Details of [ 209627-36-1 ]

CAS No. :209627-36-1
Formula : C21H29NOSi
M.W : 339.55
SMILES Code : CC(C)(C)[Si](C1=CC=CC=C1)(C2=CC=CC=C2)OC[C@H]3NCCC3
MDL No. :MFCD17018324
InChI Key :VZEUHLPSFWLCLW-SFHVURJKSA-N
Pubchem ID :11234959

Safety of [ 209627-36-1 ]

GHS Pictogram:
Signal Word:Warning
Hazard Statements:H315-H319
Precautionary Statements:P264-P280-P302+P352-P337+P313-P305+P351+P338-P362+P364-P332+P313

Application In Synthesis of [ 209627-36-1 ]

* All experimental methods are cited from the reference, please refer to the original source for details. We do not guarantee the accuracy of the content in the reference.

  • Upstream synthesis route of [ 209627-36-1 ]
  • Downstream synthetic route of [ 209627-36-1 ]

[ 209627-36-1 ] Synthesis Path-Upstream   1~1

  • 1
  • [ 1355016-90-8 ]
  • [ 52941-82-9 ]
  • [ 209627-36-1 ]
References: [1] Organic Letters, 2012, vol. 14, # 2, p. 536 - 539.
 

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