Fatty acids are key components and abundant constituents of all biological systems. As such, they play a crucial role for normal functioning at all levels of an organism. Dysfunction in fatty acid metabolism is related to various pathological states, e.g. cancer and neurodegenerative diseases. As an example, as previously reported in one of our newsletters, palmitoylation via post-translational modification plays a key role in regulating protein activity. Another example is the Ras protein, which is involved in the development of many types of cancer. It is only active and cancer-causing if it is able to bind to the cell membrane via action of a lipid anchor. Thus, fatty acids and related modifications are subject of many clinical, nutritional, and metabolic studies.

Especially Click-functionalized fatty acids as radioactivity-free labeling and tracing method are gaining ground. As an example, S-palmitoylation or N-myristylation can be tracked by incorporating bio-orthogonal alkynyl-palmitate or alkynyl-myristate into cells thus providing labeled proteins.

Furthermore, the interest in this topic increased even further due to the success of the peptide blockbuster drugs liraglutide and semaglutide. It is shown that the modification of peptides with fatty acids leads to prolonged circulation half-life in serum and thus improved performance via binding to albumin.

Another hot topic in the light of COVID-19 is the delivery of synthetic mRNA packed in lipid-based vesicles. Thus, there is strong demand for functionalized lipids for formulations.

Besides the above-mentioned applications, fatty amino acids have various other interesting properties. They may increase cell permeability of compounds and even allow substances to cross the blood-brain barrier.

Iris Biotech provides Boc- and Fmoc-protected fatty acids as well as variously functionalized derivatives, e.g. NHS-substituted active esters, azide derivatives for click chemistry and Staudinger ligation, alkyne derivatives for click chemistry, as well as fatty acid substituted amino acids. The commercial availability of such products facilitates related research and allows to gain better understanding and accelerates the development of new medicines and cancer therapies.

➔ See our selection of fatty acid building blocks available in our Webshop!

➔ You could not find the derivative you are looking for? Please feel free to contact us for a custom synthesis quote! 

References:

Disulfide-Based Self-Immolative Linkers and Functional Bioconjugates for Biological Applications; Z. Deng, J. Hu, and S. Liu; Macromol Rapid Commun 2020; 41: e1900531. https://doi.org/10.1002/marc.201900531.

Understanding Protein Palmitoylation: Biological Significance and Enzymology; Sci China Chem. 2011; 54(12): 1888-1897. https://doi.org/10.1007/s11426-011-4428-2.

Protein Palmitoylation; R. J. Deschenes; Reference Module in Life Sciences 2020; https://doi.org/10.1016/B978-0-12-819460-7.00145-6.

Synthesis of Lipidated Peptides; F. Rosi, G. Triola; Peptide Synthesis and Applications 2013; 161-189. https://doi.org/10.1007/978-1-62703-544-6_12.

New method for quicker and simpler production of lipidated proteins; Granz University of Technology; Science Daily 2019. www.sciencedaily.com/releases/2019/10/191015092245.htm.

Synthetic lipidation of peptides and amino acids: monolayer structure and properties; P. Berndt, G. B. Fields, M. Tirrell; J. Am. Chem. Soc. 1995; 117(37): 9515-9522. https://doi.org/10.1021/ja00142a019.

Peptide Lipidation – A Synthetic Strategy to Afford Peptide Based Therapeutics; R. Kowalczyk, P. W. R. Harris, G. M. Williams, S.-H. Yang, M. A. Brimble; Peptides and Peptide-based Biomaterials and their Biomedical Applications 2017; 1030: 185-227. https://doi.org/10.1007/978-3-319-66095-0_9.

Solid-Phase Synthesis of Lipidated Peptides; G. Kragol, M. Lumbierres, J. M. Palomo; H. Waldmann; Angew. Chem. Int. Ed. 2004; 116(43): 5963-5966. https://doi.org/10.1002/ange.200461150.

Roy A. Black. A self-assembled aggregate composed of a fatty acid membrane and the building blocks of biological polymers provides a first step in the emergence of protocells. Life. 2016, 6(3): 33.