Howard Hughes Medical Institute (HHMI) researchers have successfully designed and improved a new type of cancer-killing compound by performing molecular surgery to stabilize the molecule so that it selectively triggers cell death.
The idea for developing the compound emerged from the HHMI laboratory of Stanley J. Korsmeyer, who leads one of the hottest research teams currently studying programmed cell death, or apoptosis, a genetic program that executes cells that are no longer needed. Using the biologically active portion of a protein that triggers apoptosis, Korsmeyers team successfully inserted non-natural amino acids into the peptide sequence and then performed a chemical reaction that created a "staple" within the molecule, resulting in its stabilization. Korsmeyer and the papers lead author, Loren D. Walensky, who are at the Dana-Farber Cancer Institute at Harvard Medical School, reported their studies in the September 3, 2004, issue of the journal Science.
The chemical approach they applied, called hydrocarbon stapling, was developed by their collaborator Gregory L. Verdine of Harvard University, and permitted the researchers to overcome the tendency of short peptides to lose their critical three-dimensional structure – and their ability to kill cells -- when removed from the context of the complete protein. This has been one of the greatest obstacles associated with using short peptides as therapeutic agents, and has hindered their legitimacy as pharmaceutical lead compounds. By making the peptides more resistant to degradation and enabling their cellular uptake, the hydrocarbon staple overcomes classic shortcomings of peptide therapeutics.
Jennifer Michalowski | EurekAlert!
Climate Impact Research in Hannover: Small Plants against Large Waves
17.08.2018 | Leibniz Universität Hannover
First transcription atlas of all wheat genes expands prospects for research and cultivation
17.08.2018 | Leibniz-Institut für Pflanzengenetik und Kulturpflanzenforschung
New design tool automatically creates nanostructure 3D-print templates for user-given colors
Scientists present work at prestigious SIGGRAPH conference
Most of the objects we see are colored by pigments, but using pigments has disadvantages: such colors can fade, industrial pigments are often toxic, and...
Scientists at the University of California, Los Angeles present new research on a curious cosmic phenomenon known as "whistlers" -- very low frequency packets...
Scientists develop first tool to use machine learning methods to compute flow around interactively designable 3D objects. Tool will be presented at this year’s prestigious SIGGRAPH conference.
When engineers or designers want to test the aerodynamic properties of the newly designed shape of a car, airplane, or other object, they would normally model...
Researchers from TU Graz and their industry partners have unveiled a world first: the prototype of a robot-controlled, high-speed combined charging system (CCS) for electric vehicles that enables series charging of cars in various parking positions.
Global demand for electric vehicles is forecast to rise sharply: by 2025, the number of new vehicle registrations is expected to reach 25 million per year....
Proteins must be folded correctly to fulfill their molecular functions in cells. Molecular assistants called chaperones help proteins exploit their inbuilt folding potential and reach the correct three-dimensional structure. Researchers at the Max Planck Institute of Biochemistry (MPIB) have demonstrated that actin, the most abundant protein in higher developed cells, does not have the inbuilt potential to fold and instead requires special assistance to fold into its active state. The chaperone TRiC uses a previously undescribed mechanism to perform actin folding. The study was recently published in the journal Cell.
Actin is the most abundant protein in highly developed cells and has diverse functions in processes like cell stabilization, cell division and muscle...
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