Lipidated Amino Acids

Lipidated Amino Acids

Published on 27/04/2020

The tremendous success of Liraglutide and Semaglutide has moved amino acids modified with lipids into the focus of many research endeavors. Delve into the treasure trove of our lipidated amino acids!

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.

semaglutideliraglutide

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

fatty aas

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.

fatty aas

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.

fatty aas


→ 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