Peptides-Fatty Acids Conjugation

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To improve peptide pharmacokinetics, conjugating the peptide to lipids is a favored approach. Peptides-Fatty acids conjugation is obtained by fatty acid modification of the main chain structure or contralateral chain group of polypeptide drugs. Type of fatty acid includes: Caprylic acid (C8), Capric acid (C10), Lauric acid (C12), Myristic acid (C14), Palmitic acid (C16) or Stearic acid (C18) etc. Peptides-Fatty acids conjugation drugs can improve the liposolubility, intestinal mucosal permeability and absorption efficiency. It prolongs the half-life in the circulation significantly. Fatty acid conjugated peptides can also be used for a number of different applications, for example, Detemir (Levemir) is a new insulin analogue developed by Northrop. After the removal of human insulin B30 Thr, a myristic acid side chain was attached to B29 Lys, which could release the drug slowly and achieve the effect of long-term hypoglycemia.

The Structure of Myristoyl thioester and Palmitoyl esterFig1. The Structure of Myristoyl thioester and Palmitoyl ester

Application of Peptides-Fatty Acids Conjugation

Fatty acid is an important component of membrane phospholipid, which can maintain membrane fluidity and participate in the assembly of cell membrane, and it is also the basic substance of human body fat and lipids. Therefore, Peptides-Fatty acids conjugation drugs help to improve the affinity of drugs to cells, thus promoting the absorption of drugs by epithelial cells. The side chain of insulin molecule was modified with palmitic acid to obtain the more lipophilic palmitic acylated insulin. The results of isotopic tracer analysis showed that the plasma concentration of bispalmitic acid derivatives was significantly higher than that of unmodified insulin.

The enzymatic degradation of protease in vivo is one of the main reasons leading to the short half-life and low bioavailability of protein and peptide drugs. Fatty acid modification can cover the areas where protein peptides are susceptible to enzyme attack, thus delaying or inhibiting the destruction of proteolytic enzymes and prolonging the time of action in vivo.

Fatty acid can reversibly bind to human serumalbumin (HSA) in vivo. The combined complex is restricted by excessive molecular size in transmembrane transport. Therefore, fatty acid modification can prolong the retention time of drugs in vivo.

Our Services

Creative Peptides has developed a reliable method for peptides-fatty acids conjugation. Creative Peptides has a large number of researchers who will tailor the most appropriate methods to suit your needs and 100% guaranteed service for customers. Besides, the all-round literature database has been set up, which provides the technical support for products. Our company guarantees peptides-every step of metal chelates conjugation synthesis is subject to strict quality control.


  1. Wang Yue, Zhao Wei, etc. A. (2015). Advances in fatty acid modification of protein polypeptide drugs. Progress in Pharmaceutical Sciences. 39(9):651-658.
  2. Krishnakumari, V., & Nagaraj, R. (2015). N-terminal fatty acylation of peptides spanning the cationic C-terminal segment of bovine β-defensin-2 results in salt-resistant antibacterial activity. Biophysical chemistry, 199, 25-33.
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