Photoinduced hydrogel-forming caged-peptides with improved solubility

In drug design and research, we often run into the problem that bioactive substances are very difficult to dissolve. However, medicine will only be formulated of a substance that can get from the tablet / syringe to the site of action (eg. tumors, pathogens) and therefore must be soluble. We face a similar problem when we want to mimic the tissue environment (so-called peptide hydrogels) with poorly soluble peptides in cell cultures. The formation of aggregates - from insoluble peptides - play an important role in the development of quite a few diseases, too. To investigate these, experimental peptides with minimal solubility are also required.

Unfortunately, poor solubility in the case of peptides makes research particularly difficult and often impossible, as the peptides must be subjected to chromatographic purification before use, which can only be done in the form of a solution. By omitting the cleaning step, contaminants may remain in the product, which may distort the results.

This causes day-to-day problems in many research areas, limiting the range of materials that can be investigasted. Poor solubility / aggregation is usually due to the presence of structural elements where positively and negatively charged groups (e.g., lysine and glutamic acid amino acids) are located in the peptide chain, thus the chains can be aligned with opposite charges.

The planned research would make such poorly soluble peptides - which cannot be tested in practice- into "user-friendly" compounds by introducing such protecting groups to the functional groups which are responsible for aggregation, that eliminate charge (and thus precipitation) but can later be removed by ultraviolet light. This peptide derivative is expected to be soluble, purifiable and easy to handle. Upon introduction into the biological system and then exposing of the target area to UV light, the peptide is released from the protecting groups at the required site, resulting in an insoluble (and effective) form.

In the planned experiments, known photolabile protecting groups will be further modified to give derivatives suitable for this "synthetic trick".

Such blocked ("caged") peptides, in addition to those listed above, can also be used to study the aggregation, as a strong light pulse can be used to initiate the process in the measuring instrument itself.

Kata Enyedi, Zsófia Osváth, Viktor Farkas