Lipidated “fatty” amino acids have a number of intriguing applications, the most well-known being the prolongation of circulation half-life of peptide therapeutics by binding to serum albumin. This ubiquitous serum protein is able to prolong the plasma half-life of otherwise rapidly cleared drugs. Well-known examples of this application are the blockbuster drugs Liraglutide and Semaglutide.

Fatty acid linkers of Semaglutide (FAA7640) and Liraglutide (FAA3790)

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 (Blanchfield et al. 2003; Bulaj et al. 2008). Lipidation can be a means to make use of albumin as a carrier for cancer therapeutics (Hoogenboezem et al. 2018). Moreover, lipopeptides are able to trigger a T-cell dependent immune response and are thus of great interest for vaccine development (Zhu et al. 2004; Zhang et al. 2005). Finally, lipidated peptides are increasingly found in cosmetics as anti-ageing agents (Robinson et al. 2005).

We have recently added a large variety of lipidated amino acids to our portfolio. Among those are:

✓ Derivatives of Lys, Ser and Asp that give easy access to isostructural analogues
✓ Derivatives with a variety of terminal functional groups
✓ Production routes are scalable

✓ Longer homologues of norleucine & longer fatty amino acid homologues with different terminal functional groups are in development and can be supplied on custom synthesis basis.

✓ Derivatives of Arg, Asn, Cys, Gln, His, Hyp, Gly, Pro, Trp, Tyr that give easy access to new analogues.
✓ Two fatty acid residues can be attached on the same amino acid in some cases.
✓ Published applications: antimicrobial peptides, adjuvants, cancer vaccines, novel receptor agonist, cancer imaging, and peptide amphiphiles (PAs) with unusual thermal stability.
✓ Production routes are scalable.

→ Visit our Webshop to explore our selection of lipidated amino acids.
→ Contact us for the Custom Synthesis of the Fatty Amino Acid of Your Choice!

References:

• The ABC of Insulin: The Organic Chemistry of a Small Protein; K. J. Jensen, M. Ostergaard and N. M. Kumar; Chemistry 2020; n/a. doi: https://doi.org/10.1002/chem.202000337
• Harnessing albumin as a carrier for cancer therapies; E. N. Hoogenboezem and C. L. Duvall; Adv Drug Deliv Rev 2018; 130: 73-89. doi: https://doi.org/10.1016/j.addr.2018.07.011
• Discovery of the Once-Weekly Glucagon-Like Peptide-1 (GLP-1) Analogue Semaglutide; J. Lau, P. Bloch, L. Schaffer, I. Pettersson, J. Spetzler, J. Kofoed, K. Madsen, L. B. Knudsen, J. McGuire, D. B. Steensgaard, H. M. Strauss, D. X. Gram, S. M. Knudsen, F. S. Nielsen, P. Thygesen, S. Reedtz-Runge and T. Kruse; J Med Chem 2015; 58: 7370-80. doi: https://doi.org/10.1021/acs.jmedchem.5b00726
• Albumin as fatty acid transporter; G. J. van der Vusse; Drug Metab Pharmacokinet 2009; 24: 300-7. doi: https://doi.org/10.2133/dmpk.24.300
• Design, synthesis, and characterization of high-affinity, systemically-active galanin analogues with potent anticonvulsant activities; G. Bulaj, B. R. Green, H. K. Lee, C. R. Robertson, K. White, L. Zhang, M. Sochanska, S. P. Flynn, E. A. Scholl, T. H. Pruess, M. D. Smith and H. S. White; J Med Chem 2008; 51: 8038-47. doi: https://doi.org/10.1021/jm801088x
• Th-cytotoxic T-lymphocyte chimeric epitopes extended by Nepsilon-palmitoyl lysines induce herpes simplex virus type 1-specific effector CD8+ Tc1 responses and protect against ocular infection; X. Zhang, A. Issagholian, E. A. Berg, J. B. Fishman, A. B. Nesburn and L. BenMohamed; J Virol 2005; 79: 15289-301. doi: https://doi.org/10.1128/JVI.79.24.15289-15301.2005
• Topical palmitoyl pentapeptide provides improvement in photoaged human facial skin; L. R. Robinson, N. C. Fitzgerald, D. G. Doughty, N. C. Dawes, C. A. Berge and D. L. Bissett; Int J Cosmet Sci 2005; 27: 155-60. doi: https://doi.org/10.1111/j.1467-2494.2005.00261.x
• Lipopeptide epitopes extended by an Nepsilon-palmitoyl-lysine moiety increase uptake and maturation of dendritic cells through a Toll-like receptor-2 pathway and trigger a Th1-dependent protective immunity; X. Zhu, T. V. Ramos, H. Gras-Masse, B. E. Kaplan and L. BenMohamed; Eur J Immunol 2004; 34: 3102-14. doi: https://doi.org/10.1002/eji.200425166
• Synthesis, structure elucidation, in vitro biological activity, toxicity, and Caco-2 cell permeability of lipophilic analogues of alpha-conotoxin MII; J. T. Blanchfield, J. L. Dutton, R. C. Hogg, O. P. Gallagher, D. J. Craik, A. Jones, D. J. Adams, R. J. Lewis, P. F. Alewood and I. Toth; J Med Chem 2003; 46: 1266-72. doi: https://doi.org/10.1021/jm020426j