159088-48-9

Basic information

• Product Name: RAS INHIBITORY PEPTIDE
• Synonyms: RAS INHIBITORY PEPTIDE;VPPPVPPRRR-NH2;VAL-PRO-PRO-PRO-VAL-PRO-PRO-ARG-ARG-ARG;H-VAL-PRO-PRO-PRO-VAL-PRO-PRO-ARG-ARG-ARG-OH;HSOS (1149-1158) N10 SH3 BINDING DOMAIN;Sos SH3 domain inhibitor
• CAS NO: 159088-48-9
• Molecular Formula: C53H91N19O11
• Molecular Weight: 1170.41
• Mol File: 159088-48-9.mol
• Article Data: 1

Chemical Properties

• Appearance: /
• Density: 1.52±0.1 g/cm3(Predicted)
• Storage Temp.: −20°C
• PKA: 3.31±0.10(Predicted)
• CAS DataBase Reference: RAS INHIBITORY PEPTIDE(CAS DataBase Reference)
• NIST Chemistry Reference: RAS INHIBITORY PEPTIDE(159088-48-9)
• EPA Substance Registry System: RAS INHIBITORY PEPTIDE(159088-48-9)

Safety Data

• WGK Germany: 3
• Hazardous Substances Data: 159088-48-9(Hazardous Substances Data)

Usage

Description

Son of sevenless homolog 1 (Sos1) is a guanine nucleotide exchange factor (GEF) that directs the exchange of Ras-GDP to Ras-GTP by binding to SH3 domains of the growth factor receptor-bound protein 2 (Grb2), leading to the activation of ERK. Ras inhibitory peptide is a synthetic peptide that contains the sequence PVPPR, which corresponds to a region within human Sos1 that interacts with an SH3 domain of Grb2. It specifically blocks the interaction of the GEF with Grb2, preventing an interaction that is essential for Ras activation by receptor tyrosine kinases, including epidermal growth factor receptor.

Upstream product

• 15761-39-4 1-(tert-butoxycarbonyl)-L-proline 
• 13734-41-3 t-Boc-L-valine 
• 13836-37-8 Boc-Arg(Tos)-OH 

Relevant articles and documents

High affinity Grb2-SH3 domain ligand incorporating Cβ-substituted prolines in a Sos-derived decapeptide

Peptide ligands that disrupt MAPK pathways are of great interest for a better understanding of these signalling cascades and represent therefore an attractive target to control cell degenerative processes. In that context, selective disruption of the upstream Grb2/Sos complex in the Ras/MAPK cascade has focused extensive work. The Sos PPII decapeptide, which interacts with the Grb2-SH3 domains, has been modified in various positions and the best inhibitors designed so far are either dimeric ligands or peptoid analogues of the VPPPVPPRRR sequence. We report the synthesis of new Grb2 ligands in which the key Val5 residue has been replaced by a cis Cβ-substituted proline. Both fluorescence and ITC assays have been employed to measure the affinity of these substituted peptides for a recombinant Grb2 protein. Whereas proline in position 5 completely abolished the binding potency, a cis Cβ-methyl-L-proline restored the affinity. Other cis Cβ-proline substituents led to a complete loss of binding potency. Combining the best modifications: a cis Cβ-methylproline 5, N-acetylation, C-carboxamide and dimerization yielded a 560-fold affinity enhancement compared to the wild-type VPPPVPPRRR sequence. This study shows that Cβ-substituted prolines may constitute a new alternative for PPII ligands, combining entropy and enthalpy beneficial effects.