Related Experiment Video

Updated: Jun 21, 2026

Peptide-based Identification of Functional Motifs and their Binding Partners
14:28

Peptide-based Identification of Functional Motifs and their Binding Partners

Published on: June 30, 2013

Inhibiting the inhibitors: retro-inverso Smac peptides

Julia Hossbach1, Elke Michalsky, Peter Henklein

  • 1Charité - Universitätsmedizin Berlin, Institute of Physiology, Structural Bioinformatics Group, Arnimallee 22, 14195 Berlin, Germany. Julia.Hossbach@charite.de

Peptides
|August 18, 2009
PubMed

Insights

Scientists designed Smac-derived peptides using bioinformatics to overcome resistance to apoptosis-inducing anti-cancer drugs. These modified peptides improve cancer cell sensitivity to apoptosis, offering a potential new therapeutic strategy.

Area of Science:

  • Biochemistry
  • Molecular Biology
  • Drug Discovery

Background:

  • Resistance to apoptosis-inducing anti-cancer drugs is a major therapeutic challenge.
  • Overexpression of Inhibitors of Apoptosis Proteins (IAPs) prevents cancer cell death.
  • Natural Smac peptides are unstable in vivo, limiting their therapeutic use.

Purpose of the Study:

  • To design novel Smac-derived peptides to overcome IAP-mediated therapy resistance.
  • To enhance the stability and efficacy of Smac peptides for cancer treatment.
  • To identify Smac peptides that can re-sensitize IAP-high expressing tumor cells to apoptosis.

Main Methods:

  • Bioinformatic approaches were used to design Smac-derived peptides.
  • Amino acid substitutions with unnatural amino acids were employed to improve peptide stability and function.
  • Computational docking was utilized to filter and select promising peptide candidates.
  • In vitro testing of Smac-derived peptides in Hodgkin Lymphoma cell lines.

Main Results:

  • Smac-derived peptides incorporating unnatural amino acids demonstrated improved apoptosis sensitivity in tumor cells.
  • Computational docking successfully identified Smac peptides with significant binding affinity to IAPs.
  • Tested peptides showed potential in re-sensitizing IAP-expressing Hodgkin Lymphoma cells.

Conclusions:

  • Bioinformatically designed Smac-derived peptides offer a promising strategy to combat anti-cancer drug resistance.
  • Unnatural amino acid incorporation enhances the therapeutic potential of Smac peptides.
  • These novel peptides warrant further investigation for cancer therapy, particularly in IAP-overexpressing tumors.

More Related Videos

Development of Inhibitors of Protein-protein Interactions through REPLACE: Application to the Design and Development Non-ATP Competitive CDK Inhibitors10:33

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

Related Concept Videos

Inhibitors of Viral Protein Synthesis01:30

Inhibitors of Viral Protein Synthesis

Protein synthesis is indispensable for viral replication, as viruses lack the cellular machinery required for this process and must hijack the host's translational apparatus. In response, host cells deploy a critical innate immune defense involving interferons, specialized cytokines that play a central role in inhibiting viral propagation.Upon viral detection, infected cells release interferons that bind to receptors on adjacent uninfected cells, activating the JAK-STAT signaling pathway and...
Inhibitors of Virion Maturation and Assembly01:19

Inhibitors of Virion Maturation and Assembly

As part of their replication cycle, certain viruses synthesize long precursor proteins called polyproteins within infected host cells. In human immunodeficiency virus (HIV), two major polyproteins are produced: Gag and Gag-Pol. The Gag polyprotein supplies the structural components of the virus, while Gag-Pol includes essential viral enzymes such as reverse transcriptase, integrase, and protease. After synthesis, these polyproteins move to the host cell membrane, where they assemble into an...
Feedback Inhibition00:46

Feedback Inhibition

Biochemical reactions are occurring constantly in cells, converting starting substances to different products, usually with the help of enzymes that speed the reactions. Without enzymes, it would take far too long for most reactions to occur to be useful to the cell!
Enzyme Inhibition01:30

Enzyme Inhibition

Inhibitors are molecules that reduce enzyme activity by binding to the enzyme. In a normally functioning cell, enzymes are regulated by a variety of inhibitors. Drugs and other toxins can also inhibit enzymes. Some inhibitors bind to the enzyme’s active site, while others inhibit enzymatic activity by binding to other sites on the protein structure.
Inhibitors of Gram-positive Cell Wall Synthesis01:23

Inhibitors of Gram-positive Cell Wall Synthesis

Bacterial cell walls are typically rigid structures composed mainly of peptidoglycan, a mesh-like polymer that provides mechanical strength and maintains cell shape. The synthesis of peptidoglycan is a crucial process in bacterial growth and serves as a primary target for many antibiotics.Mechanism of Action of Beta-Lactam AntibioticsBeta-lactam antibiotics, such as penicillin, inhibit peptidoglycan synthesis in actively growing cells. These antibiotics share a characteristic four-membered...
Inhibitors of Bacterial Protein Synthesis01:25

Inhibitors of Bacterial Protein Synthesis

Aminoglycosides constitute a highly potent class of bactericidal antibiotics that exert their antimicrobial effects by targeting the bacterial ribosome, specifically disrupting protein synthesis. These polycationic molecules consist of amino-modified sugars linked via glycosidic bonds to an aminocyclitol core such as 2-deoxystreptamine or streptamine. Their strong positive charges facilitate tight binding to the negatively charged phosphate backbone of ribosomal RNA (rRNA), primarily at the 16S...