The discovery could help speed the development of peptide-based drugs against diseases including cancer. UB scientists say the methods they pioneered are simpler than existing techniques, one of which employs an expensive ruthenium catalyst to connect chemical side chains that protrude from the main body of helical peptides.
"There's a lot of potential here. Our chemistry is unique," said Qing Lin, the UB assistant professor of chemistry who led the research. "There are not that many new drug targets out there today, which partly explains the declining number of FDA-approved new drugs in recent years. So there's a need to come up with new technologies that can overcome this barrier. To this end, stapled peptides could open a whole host of new targets for therapies."
Stapled peptides work as treatments against disease by binding tightly to target proteins within cells, thus disrupting specific protein-protein interactions that regulate many biological processes, including response to stress, signaling within cells, and cell death.
In their native state, peptides -- short strings of amino acids -- shift between different shapes, including a helix, sheet and random coil. Stapling the peptides' side chains encourages the peptides to adopt and stay in a helix, which enables them to enter cells more easily. The helical conformation also makes it more difficult for enzymes to break the peptides down, Lin said.
The two processes Lin's team developed for stapling peptides are efficient, producing stapled peptides in high yields, said Timothy Dee, a commercialization manager for UB's Office of Science, Technology Transfer and Economic Outreach (STOR). Through STOR, UB is applying for patents to cover both stapling methods.
"Photoclick stapling," the first approach, involves synthesizing peptides that have alkenes in one side chain and tetrazoles in another. Under ultraviolet light, the two side chains form chemical bonds with one another.
A paper on photoclick stapling appeared online in Bioorganic and Medicinal Chemistry Letters in January and will appear later this year in the journal's print edition. Researchers first published on the subject in 2009 in Chemical Communications.
The second stapling technique Lin and his colleagues devised requires the synthesis of peptides carrying a pair of amino acids called cysteines that contain sulfur in their side chains. When scientists expose these peptides to a chemical that reacts selectively with the sulfur atoms, the chemical forms a "staple" that connects the two cysteine side chains.
Experts believe stapled peptides could treat a wide variety of health problems, including cancer and inflammatory, metabolic and infectious diseases. As evidence of the technology's promise, a company formed in 2005 to commercialize a ruthenium-based stapling method developed at Harvard University has reportedly raised about $60 million in venture capital and landed a deal with pharmaceutical giant Roche that could be worth more than $1 billion over time.
"The field is large enough for multiple players," Lin said. "Stapling is a technology that many people believe will create a new class of drug therapies, hitting new targets that other therapies can't. Our chemistry is distinct from what's already out there."
Lin and his group are particularly interested in developing anti-cancer therapeutics that increase the efficacy of chemotherapy by instructing cancer cells to self-destruct through "programmed cell death," a process called apoptosis.
The University at Buffalo is a premier research-intensive public university, a flagship institution in the State University of New York system and its largest and most comprehensive campus. UB's more than 28,000 students pursue their academic interests through more than 300 undergraduate, graduate and professional degree programs. Founded in 1846, the University at Buffalo is a member of the Association of American Universities.
Charlotte Hsu | EurekAlert!
Water forms 'spine of hydration' around DNA, group finds
26.05.2017 | Cornell University
How herpesviruses win the footrace against the immune system
26.05.2017 | Helmholtz-Zentrum für Infektionsforschung
Staphylococcus aureus is a feared pathogen (MRSA, multi-resistant S. aureus) due to frequent resistances against many antibiotics, especially in hospital infections. Researchers at the Paul-Ehrlich-Institut have identified immunological processes that prevent a successful immune response directed against the pathogenic agent. The delivery of bacterial proteins with RNA adjuvant or messenger RNA (mRNA) into immune cells allows the re-direction of the immune response towards an active defense against S. aureus. This could be of significant importance for the development of an effective vaccine. PLOS Pathogens has published these research results online on 25 May 2017.
Staphylococcus aureus (S. aureus) is a bacterium that colonizes by far more than half of the skin and the mucosa of adults, usually without causing infections....
Physicists from the University of Würzburg are capable of generating identical looking single light particles at the push of a button. Two new studies now demonstrate the potential this method holds.
The quantum computer has fuelled the imagination of scientists for decades: It is based on fundamentally different phenomena than a conventional computer....
An international team of physicists has monitored the scattering behaviour of electrons in a non-conducting material in real-time. Their insights could be beneficial for radiotherapy.
We can refer to electrons in non-conducting materials as ‘sluggish’. Typically, they remain fixed in a location, deep inside an atomic composite. It is hence...
Two-dimensional magnetic structures are regarded as a promising material for new types of data storage, since the magnetic properties of individual molecular building blocks can be investigated and modified. For the first time, researchers have now produced a wafer-thin ferrimagnet, in which molecules with different magnetic centers arrange themselves on a gold surface to form a checkerboard pattern. Scientists at the Swiss Nanoscience Institute at the University of Basel and the Paul Scherrer Institute published their findings in the journal Nature Communications.
Ferrimagnets are composed of two centers which are magnetized at different strengths and point in opposing directions. Two-dimensional, quasi-flat ferrimagnets...
An Australian-Chinese research team has created the world's thinnest hologram, paving the way towards the integration of 3D holography into everyday...
24.05.2017 | Event News
23.05.2017 | Event News
22.05.2017 | Event News
26.05.2017 | Life Sciences
26.05.2017 | Life Sciences
26.05.2017 | Physics and Astronomy