Stapled Peptides

Stapled peptides are synthetic 'mini-proteins' that are locked into their bioactive α-helical secondary structure, so conferring high specificity, high potency and resistance to enzymatic degradation. They target protein-protein interactions (PPIs), opening up a range of targets that were previously considered to be undruggable.

Products
Background
文献
Cat. No. 产品名称/活性
6531 NLS-StAx-h
Wnt signaling inhibitor; inhibits beta -catenin-transcription factor interactions
6567 RI-STAD 2
AKAP disruptor; selectively blocks PKA-RI-AKAP interaction; cell permeable
6708 SAH-EZH2
EZH2/EDD interaction inhibitor; suppresses PCR2 complex function
6920 SAH-SOS1A
KRas/SOS1 interaction inhibitor
6477 SAHM1
Notch pathway inhibitor; prevents Notch complex assembly
6566 STAD 2
AKAP disruptor; selectively blocks PKA-RII-AKAP interaction; cell permeable
6575 StRIP16
Rab8a GTPase-binding stapled peptide

Peptides are an alternative class of drug molecule, which are being used to therapeutically target previously undruggable protein-protein interactions (PPIs). The interacting surfaces of PPIs are shallow/flat, large and non-hydrophobic making them ideal targets for peptides, which are able to mimic a native protein. Peptides are highly selective, but often suffer from poor cell permeability, plasma stability and bioavailability.

Stapling a peptide overcomes these limitations by the formation of a synthetic mini-protein, which is locked into a bioactive α-helical secondary structure by site-specific insertion of a chemical 'brace'. Chemical restriction of conformation in this way improves the pharmacological properties of peptides. Stapled peptides possess:

  • Increased potency due to stabilization of favorable binding conditions
  • Decreased enzymatic degradation due to blockade of protease active sites
  • Improved selectivity for intended target decreasing off-target effects
  • Improved affinity on an atomic level without requiring additional interactions

Targeting protein-protein interactions (PPIs) with stapled peptides opens an expanded range of targets for therapeutic intervention, which were previously considered to be undruggable. Transcription factors which were thought to be undruggable have been successfully inhibited by stapled peptides; for example, ALRN-6924 is under clinical development as an anti-cancer drug targeting HDM2/p53. Stapled peptides have also been designed to disrupt enzymes, multidrug resistance efflux pumps and membrane receptor dimers.

Literature for Stapled Peptides

Tocris offers the following scientific literature for Stapled Peptides to showcase our products. We invite you to request* or download your copy today!

*Please note that Tocris will only send literature to established scientific business / institute addresses.


New Product Guide

New Product Guide (Fall/Winter 2018/2019)

Our new product guide highlights over 190 new products added to the Tocris Bioscience range during the second half of 2018.

  • 7-TM Receptors
  • Enzymes
  • Enzyme-Linked Receptors
  • Ion Channels
  • Nuclear Receptors
  • Transporters
  • Chemogenetics
  • Epigenetics
  • Fluorescent Imaging
  • PROTACs
  • Signal Transduction
  • Stem Cells