Building New “Molecular Keys” from Ray-Derived Peptides

Jul 23, 2026 | News

Marine life hides not only unusual shapes and colours, but also tiny molecules that may offer new ideas for drug discovery. Szeged researchers took part in a recent international study in which scientists designed new hybrid molecules based on ray-derived peptides and examined how these molecules behave in cells and in different molecular interactions.

One of the major challenges in drug development is that a compound should not only be potent, but should also act as precisely as possible, at the right place and in the right way. Many diseases, including malignant tumours, often require combination therapy, meaning that several drugs are given at the same time. However, different active compounds can behave very differently in the body: they may enter the body at different rates, distribute differently between tissues, or break down at different speeds. This can make their combined use considerably more complicated.

Molecular hybridisation offers an exciting possible approach to this problem. The idea is to connect two molecular fragments with different biological properties into a single new structure. In simple terms, it is a little like trying to create a new key from the teeth of two different keys, with the hope that it may fit more than one lock.

The two new molecules examined in this study, PK01# and PK02#, are such hybrid peptides. One part of them comes from dermorphin, a known opioid peptide originally discovered in a South American frog and recognised for its very strong pain-relieving activity. The other part is based on a peptide identified in the ray species Raja porosa, which has previously shown surprising anticancer activity. Marine peptides are especially interesting because ocean organisms have adapted to highly diverse environments, and their molecules often reflect this diversity. These small protein fragments can have varied structures and may serve as starting points for several types of biological activity.

The researchers first examined whether the new hybrid molecules could bind to a receptor associated with pain relief, the µ-opioid receptor. The experiments showed that both new peptides were able to bind to this receptor and partially activate it. However, there was an important difference between them: PK01# bound more strongly than PK02#. This suggests that even a single building-block change can noticeably alter the behaviour of such a tiny molecular construction.

The next question was whether these hybrid peptides affect the viability of cancer cells. The researchers tested them on several cell lines and found that, overall, they did not show the same strong cell-killing effect as the original ray-derived peptide on its own. However, in one case, PK02# was able to reduce the metabolic activity of cells at the highest concentration tested.

At first, this may sound disappointing, but in drug discovery, “it did not kill the cells” is not necessarily bad news. For a new molecule, it is just as important to understand how safe it is, how stable it is, and which receptors it can bind to. The tests showed that the peptides caused only low levels of damage to red blood cells, especially in the case of PK01#. This may be a favourable sign, although it certainly does not mean that these molecules could already be used as drugs.

The researchers also used computer modelling to explore how these new molecules might behave. In this type of analysis, the molecule and the target protein can be imagined as a key and a lock: the software examines how well they might fit together. The two peptides were tested against two important proteins. One was the µ-opioid receptor, which the laboratory experiments confirmed they can bind to. The other was EGFR, a protein that plays an important role in the growth and survival of cells in many tumour types.

The main message of the study is therefore not that a new anticancer drug has been discovered. Rather, the researchers successfully created and characterised two marine-derived hybrid peptides that retained their ability to bind to receptors, while showing only limited effects on cells. This also indicates that linking peptides together can modify their biological effects. This type of research contributes to the early mapping stage of drug development, helping scientists understand which molecular building blocks may be worth optimising further.

The full study is available here:https://doi.org/10.3390/md24050181