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Related Concept Videos

Small GTPases - Ras and Rho01:24

Small GTPases - Ras and Rho

Ras and Rho are small monomeric GTPases that act downstream of receptor tyrosine kinase (RTK) and regulate various cellular processes. These GTPases switch between active and inactive states by binding to guanine nucleotides.
Three regulatory proteins control their activity:
The Ras Gene02:38

The Ras Gene

The Ras-gene-encoded proteins are regulators of signaling pathways controlling cell proliferation, differentiation, or cell survival. The Ras-gene family in humans constitutes three primary members—the HRas, NRas, and KRas. These genes code for four functionally distinct yet closely related proteins—the HRas, NRas, KRas4A, and KRas4B. The involvement of mutant Ras genes in human cancer was first discovered in 1982 and is among the most common causes of human tumorigenesis.
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GPCR Desensitization01:12

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G protein-coupled receptor (GPCR) signaling plays a crucial role in cell functioning. GPCR desensitization is an equally essential process. It allows cells to respond to changing environments and regain sensitivity to new stimuli while preventing unnecessary stimulation when no longer needed. Prolonged exposure to stimuli leads to GPCR desensitization. It involves blocking the receptors from binding and activating additional G proteins. This inhibits activation of downstream effectors, thereby...
Amplifying Signals via Enzymatic Cascade01:22

Amplifying Signals via Enzymatic Cascade

When a ligand binds to a cell-surface receptor, the receptor's intracellular domain changes shape, which may either activate its enzyme function or allow its binding to other molecules. The initial signal is amplified by most signal transduction pathways. This means that a single ligand molecule can activate multiple molecules of a downstream target. Proteins that relay a signal are most commonly phosphorylated at one or more sites, activating or inactivating the protein. Kinases catalyze the...
GPCRs Regulate Adenylyl Cylase Activity01:09

GPCRs Regulate Adenylyl Cylase Activity

Some GPCRs transmit signals through adenylyl cyclase (AC), a transmembrane enzyme. AC helps synthesize second messenger cyclic adenosine monophosphate (cAMP). AC catalyzes cyclization reaction and converts ATP to cAMP by releasing a pyrophosphate. The pyrophosphate is further hydrolyzed to phosphate by the enzyme pyrophosphatase, which drives cAMP synthesis to completion. However, cAMP is rapidly degraded to 5′ AMP by the enzymes phosphodiesterase (PDE), preventing overstimulation of cells.
Two...
Rab Proteins01:14

Rab Proteins

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Updated: May 12, 2026

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors
10:33

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors

Published on: October 26, 2015

Inhibition of Ras-Effector Interaction by Cyclic Peptides.

Xianghong Wu1, Punit Upadhyaya, Miguel A Villalona-Calero

  • 1Department of Chemistry and Biochemistry, The Ohio State University, 100 West 18 Avenue, Columbus, OH 43210, U. S. A. ; Tel: 614-688-4068.

Medchemcomm
|April 16, 2013
PubMed
Summary
This summary is machine-generated.

Researchers created millions of unique cyclic peptides to find K-Ras inhibitors. They discovered compounds with high affinity that block K-Ras interactions with other proteins, offering new therapeutic strategies.

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Published on: March 9, 2012

Area of Science:

  • Medicinal Chemistry
  • Molecular Biology
  • Drug Discovery

Background:

  • K-Ras is a key oncogene frequently mutated in human cancers.
  • Targeting K-Ras remains challenging due to its complex structure and function.
  • Disrupting K-Ras effector interactions is a promising therapeutic strategy.

Purpose of the Study:

  • To develop a large combinatorial library of cyclic peptides for screening.
  • To identify novel cyclic peptides that bind to and inhibit K-Ras.
  • To find compounds that disrupt K-Ras effector protein interactions.

Main Methods:

  • Synthesis of a 6 × 10^6 cyclic peptide library using the one bead-two compound format.
  • Each bead contained a unique cyclic peptide and a corresponding encoding tag.
  • Screening the library against K-Ras to identify binding compounds.

Main Results:

  • Identified cyclic peptides that bind to K-Ras with submicromolar affinity.
  • Discovered compounds that effectively disrupt K-Ras interaction with effector proteins.
  • Demonstrated the utility of the one bead-two compound library for drug discovery.

Conclusions:

  • The synthesized cyclic peptide library is a valuable tool for identifying K-Ras inhibitors.
  • Novel cyclic peptides targeting K-Ras effector interactions were discovered.
  • These findings provide a foundation for developing new K-Ras-targeted cancer therapies.