Researchers from the HUN-REN Biological Research Centre (SZBK) in Szeged have taken part in an international study investigating the anti-cancer potential of hybrid molecules created from peptides found in a stingray and a South American frog, the institute announced.
One of the major challenges in drug development is designing compounds that not only have strong therapeutic effects but also act precisely where they are needed. Treating diseases such as cancer often requires combination therapies involving multiple drugs, whose different absorption, distribution and metabolism profiles can complicate treatment.
To address this challenge, researchers explored molecular hybridization, a technique that combines fragments of two biologically active molecules into a single new compound with the aim of integrating their beneficial properties.
The hybrid molecules examined in the study combine part of dermorphin, a powerful opioid peptide originally isolated from a South American frog, with a fragment of an anti-tumour peptide discovered in the stingray species Raja porosa.
Marine peptides have attracted increasing scientific interest because organisms living in the oceans have evolved unique molecular structures that can exhibit a wide range of biological activities.
The researchers first examined whether the newly created hybrid peptides could bind to a receptor involved in pain relief. Both molecules successfully attached to the receptor and acted as partial activators. However, differences in their binding strength suggested that even a single amino acid change can significantly alter the behaviour of these short peptide molecules.
The team also investigated the effects of the hybrid peptides on cancer cells. Overall, the compounds did not demonstrate the same level of tumour cell-killing activity as the stingray-derived peptide alone. However, one of the hybrid molecules reduced the metabolic activity of cancer cells at the highest concentration tested.
Importantly, the peptides showed only limited damaging effects on red blood cells, indicating low toxicity under the experimental conditions.
In addition to laboratory testing, the researchers used computer modelling to examine how the hybrid molecules interact both with the pain-related receptor and with a protein whose mutations are associated with certain forms of lung and colorectal cancer.
According to the study, published in the peer-reviewed journal Marine Drugs, the research successfully developed and characterized two novel marine-derived hybrid peptides that retained their receptor-binding properties while exhibiting more moderate cellular effects. The findings suggest that combining peptide fragments can significantly modify their biological activity and may support the future development of more targeted therapeutic compounds.
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