The therapeutic potential of peptides
Animal venoms as natural resource for new drugs
2021-02-10
(Press-News.org) "Insulin is a prime example for a successful peptide drug that has been essential for the health of millions of diabetic patients in the past 100 years," says Markus Muttenthaler, who leads research groups at the Institute of Biological Chemistry of the Faculty of Chemistry at University in Vienna as well as at the Institute for Molecular Bioscience, at the University of Queensland in Brisbane.
Worldwide, peptide therapeutics account for 5% of the global pharmaceutical market, with global sales exceeding US$ 50 billion. More than 150 peptides are in clinical development and another 400-600 peptides undergoing preclinical studies.
Peptide drugs have a distinct space in the pharmaceutical landscape. They are smaller than small molecule drugs, which hold the largest share of therapeutics on the market, and larger than genetically produced biologics such as antibodies. Compared to small molecules, peptides are often more potent and selective, and thus have fewer side effects; compared to antibodies, their production is more economic and they have certain advantages in cancer research, e.g. they can penetrate (tumour) tissue more easily. However, 90% of peptide drugs need to be injected, since the digestive system breaks them down rapidly when taken orally.
Vast peptide libraries
According to the corresponding authors, Assoc. Prof. Markus Muttenthaler and his Australian colleague, Prof. Paul F. Alewood, the increased interest in peptide drugs demands "efficient strategies for the discovery of therapeutic leads". A key trend in peptide drug discovery is the establishment and directed evolution of vast peptide libraries based on latest display technologies, a concept that has been recognised with the Nobel Prize in Chemistry in 2018.
The systematic exploration of animal venoms is another key trend that drives peptide drug discovery, and "allows us to take advantage of the vast natural and over millions of years evolutionary-selected peptide libraries for therapeutic lead discovery", says Muttenthaler, who is very active in this space.
New insights
In a recent study, Muttenthaler's team chemically conjugated a spider-venom peptide with a scorpion-venom peptide. Both substances use different mechanisms to block an ion channel that plays an important role in pain signalling. "Linking the two different binding mechanisms resulted in irreversible blockage of the ion channel, and the concept might be useful for prolonged pain relief," says Muttenthaler.
In a second study, his team, together with Christophe Duplais' group in French Guyana, analysed the venom of the Brazilian ant species, Pseudomyrmex penetrator, and synthesised and characterised the most active component. The potent paralytic effect of the isolated venom peptide against plant pests could serve as a promising lead for environmentally friendly and less hazardous biopesticides.
Identifying the right space within the drug landscape
Peptides are signalling molecules of life that control many physiological functions: "When investigating natural products and complex antibiotics such as vancomycin, it can often take years to establish a chemical synthesis; newly discovered peptide compounds, however, can be synthesised in days, which greatly accelerates the research and development of new peptide therapeutics", Muttenthaler explains. "It is however crucial to identify the right pharmacological space where your peptide drug can outperform small molecule drugs or biologics."
INFORMATION:
Publication in Nature Reviews Drug Discovery:
Trends in peptide drug discovery, by Markus Muttenthaler, Glenn F. King, David J. Adams, and Paul F. Alewood, in: Nature Reviews Drug Discovery 2021,
DOI:10.1038/s41573-020-00135-8
ELSE PRESS RELEASES FROM THIS DATE:
2021-02-10
Children with epilepsy sleep poorly compared to healthy children, and are more likely to experience disruptions such as night terrors, sleep walking or sleep disordered breathing, according to a new study.
A team at the University of Birmingham's Centre for Human Brain Health analysed 19 published studies on sleep and epilepsy in children and adolescents to try to better understand and articulate the links between them.
Their findings, published in Sleep Medicine Reviews, highlight the significantly poorer sleep experienced by children and adolescents with epilepsy, and present a strong argument for screening children for sleep problems as an integral part of diagnosis and management of the condition.
Lead author Alice Winsor explains: "We know that sleep and epilepsy ...
2021-02-10
Among the most active fields of research in modern physics, both at an academic level and beyond, are quantum computation and communication, which apply quantum phenomena such as superposition and entanglement to perform calculations, or to exchange information. A number of research groups around the world have built quantum devices that are able to perform calculations faster than any classical computer. Yet, there is still a long way to go before these devices can be converted into marketable quantum computers. One reason for this is that both quantum computation and ...
2021-02-10
A new study shows that proteins called IAPs, which can trigger programmed cell death, are inhibited by a specific chemical modification, and reveals that they play a wider role in protein quality control than previously assumed.
N-terminal acetylation - the attachment of an acetyl group (CH3-COO-) directly to the N-terminus of a protein - is one of the most common modifications found in the protein complements of higher organisms. The chemical tag has been linked to a wide variety of cellular signaling pathways. Now researchers led by Tanja Bange (Institute of Medical Psychology, Ludwig-Maximilians-Universitaet (LMU) in Munich) have shown that N-terminal acetylation shields certain proteins from degradation, and inhibits programmed cell death ('apoptosis'). ...
2021-02-10
People who eat a Mediterranean-style diet--particularly one rich in green leafy vegetables and low in meat--are more likely to stay mentally sharp in later life, a study shows.
Closely adhering to a Mediterranean diet was associated with higher scores on a range of memory and thinking tests among adults in their late 70s, the research found.
The study found no link, however, between the Mediterranean-style diet and better brain health.
Markers of healthy brain ageing - such as greater grey or white matter volume, or fewer white matter lesions--did not differ between those regularly eating a Mediterranean diet and those who did not.
These ...
2021-02-10
Washington, DC - February 9, 2021 - A team of investigators from the Republic of China has discovered that 6 drugs previously approved by the US Food and Drug Administration (FDA) for other indications could be repurposed to treat or prevent COVID-19. The research is published in Antimicrobial Agents and Chemotherapy, a journal of the American Society for Microbiology.
Using FDA-approved drugs saves time -- the drugs don't need to go through the FDA approval process again -- making them available quickly to treat patients who need them.
The research shows that the investigators screened 2 large drug libraries cumulatively containing 3,769 FDA-approved drugs and found drugs that can inhibit 2 protein-cutting ...
2021-02-10
MOSCOW, Idaho -- Feb. 9, 2021 -- Breastfeeding women with COVID-19 do not pass along the SARS-CoV-2 virus in their milk but do transfer milk-borne antibodies that are able to neutralize the virus, a multi-institutional team of researchers led by the University of Idaho reported.
The team analyzed 37 milk samples submitted by 18 women diagnosed with COVID-19. None of the milk samples were found to contain the virus, but nearly two-thirds of the samples did contain two antibodies specific to the virus.
"Taken together, our data do not support maternal-to-infant transmission of SARS-CoV-2 via milk," the researchers reported ...
2021-02-10
ALBUQUERQUE, N.M. -- Something lurks beneath the Arctic Ocean. While it's not a monster, it has largely remained a mystery.
According to 25 international researchers who collaborated on a first-of-its-kind study, frozen land beneath rising sea levels currently traps 60 billion tons of methane and 560 billion tons of organic carbon. Little is known about the frozen sediment and soil -- called submarine permafrost -- even as it slowly thaws and releases methane and carbon that could have significant impacts on climate.
To put into perspective the amount of greenhouse gases in submarine permafrost, humans have released about 500 billion tons of carbon into the atmosphere since the Industrial Revolution, said Sandia National Laboratories geosciences engineer ...
2021-02-10
The Texas Heart Institute (THI) has announced that a research team led by Dr. Mehdi Razavi, Director of Electrophysiology Clinical Research & Innovations, has developed a breakthrough new ex vivo benchtop system for evaluating the effects of ablation systems on excised tissues and assessing potential damage to collateral heart tissues. The unique system allows for fast and easy benchtop assessments rather than using costly in vivo tests. Critical findings associated with this innovation are outlined in a study published in the Journal of Cardiovascular Physiology.
The new ablation method evaluated by Dr. Razavi and team is being ...
2021-02-10
Washington, February 10, 2021--After the COVID-19 crisis hit last March, federal student aid applications among potential college freshmen in California dropped 14 percent between mid-March and mid-August, relative to prior years. While there were also initial declines in applications among current undergraduates and graduate students, these quickly recovered and ended 8 percent higher relative to prior years. The findings, published today in Educational Researcher, a peer-reviewed journal of the American Educational Research Association, are from the first academic study conducted on this topic.
Using data from the ...
2021-02-10
ANN ARBOR, Mich. and VANCOUVER, B.C. (February 10, 2021) - After screening more than 1,100 independently assessed, point-of-care COVID-19 tests, researchers at NSF International and Novateur Ventures have identified 5 direct (antigen/RNA) tests for detection of acute infection and 6 indirect (antibody) tests for detection of prior infection that meet the recently published World Health Organization (WHO) "desirable" Target Product Profile (TPP) criteria. The researchers hope their work will help communities and healthcare systems make more informed decisions when choosing rapid, point-of-care COVID-19 ...
LAST 30 PRESS RELEASES:
[Press-News.org] The therapeutic potential of peptides
Animal venoms as natural resource for new drugs