Význam peptidových terapeutik v posledních letech neustále roste. Peptidy jako potenciální léčiva mají mnoho příznivých chemických a farmakologických vlastností, počínaje jejich velkou rozmanitostí a konče vysokou afinitou k různým druhům přirozených receptorů. Přes tyto a další přínosy však mají i své nevýhody. Mají omezenou stabilitu v organismu v důsledku rychlé degradace a vylučování. Pro dosažení co nejlepšího farmakologického účinku je žádoucí hledat vhodné způsoby modifikace peptidů vedoucí k jejich vyšší stabilitě bez ztráty afinity k příslušným receptorům. Existuje mnoho různých způsobů modifikace peptidů. V této práci jsou shrnuty v současnosti používané syntetické přístupy potenciálně vedoucí ke zlepšení klíčových vlastností peptidů v roli nových perspektivních léčiv se zaměřením na lipidizaci. Tato práce zároveň nabízí přehled lipidizovaných peptidových léčiv, které jsou momentálně dostupné na trhu.
Peptide therapeutics are becoming increasingly important in the quest for effective compounds to treat various difficult-to-cure diseases. As potential therapeutics, peptides have many favorable chemical and pharmacological properties, ranging from their great diversity to their high affinity to various types of natural receptors. However, despite these and other advantages, they also have their pitfalls, such as a very limited stability in the organism. They have a short half-life and tend to be excreted from the body very quickly. In order to achieve a better pharmacological effect, it is desirable to find new means of modifying peptides to enable them to be used as effective drugs. There are many ways of altering the peptide structure. In this review, we summarize the approaches currently used to modify the peptide constitution with a focus on lipidization. Simultaneously this review summarizes all lipidized peptide-based therapeutics that are currently on the market.
Peptides, as potential therapeutics continue to gain importance in the search for active substances for the treatment of numerous human diseases, some of which are, to this day, incurable. As potential therapeutic drugs, peptides have many favorable chemical and pharmacological properties, starting with their great diversity, through their high affinity for binding to all sort of natural receptors, and ending with the various pathways of their breakdown, which produces nothing but amino acids that are nontoxic to the body. Despite these and other advantages, however, they also have their pitfalls. One of these disadvantages is the very low stability of natural peptides. They have a short half-life and tend to be cleared from the organism very quickly. Their instability in the gastrointestinal tract, makes it impossible to administer peptidic drugs orally. To achieve the best pharmacologic effect, it is desirable to look for ways of modifying peptides that enable the use of these substances as pharmaceuticals. There are many ways to modify peptides. Herein we summarize the approaches that are currently in use, including lipidization, PEGylation, glycosylation and others, focusing on lipidization. We describe how individual types of lipidization are achieved and describe their advantages and drawbacks. Peptide modifications are performed with the goal of reaching a longer half-life, reducing immunogenicity and improving bioavailability. In the case of neuropeptides, lipidization aids their activity in the central nervous system after the peripheral administration. At the end of our review, we summarize all lipidized peptide-based drugs that are currently on the market.
