Chemical modifications of peptides introduced strategically at potential enzymatic cleavage sites may dramatically increase the in vivo stability of peptide drug candidates. One simple approach to stabilizing a peptide is to modify the side-chains of some of the amino acids involved in the protease recognition site. The residues of interest are replaced by natural or non-natural amino acids with chemically similar side-chains. The introduction of non-natural amino acids generates modifications in the secondary and tertiary structures of a peptide, and is used to further enhance the stability and activity of peptide sequences.
More than 700 amino acids that are the so-called unusual, unnatural, or nonproteinous amino acids have been found in nature in the free zwitterionic form or as constituents of peptides. These amino acids have attracted much attention from scientists due to their important biological activities as antibiotics, metal chelators, neurotoxins, enzyme inhibitors, etc.
Creative Peptides specialized in the custom synthesis of unusual and non-natural amino acids modification, providing a confidential and efficient service at competitive prices. Every step of peptide synthesis is subject to Creative Peptides’ stringent quality control. Typical delivery specifications include:
Unusual and non-natural amino acids are chemically modified amino acids that differ from the standard 20 amino acids. They can be naturally occurring or synthetically produced and are often used to enhance the stability, activity, and selectivity of peptides.
Modifying amino acids, especially at enzymatic cleavage sites, can increase the stability of peptide drugs by preventing protease recognition and enhancing resistance to degradation, thus improving their in vivo half-life.
D-amino acids, the mirror image of the naturally occurring L-amino acids, are commonly used to stabilize peptides by reducing enzymatic degradation, improving binding specificity, and extending peptide half-life in vivo.
Non-natural amino acids can introduce structural diversity and improve the bioactivity of peptides. These modifications can enhance receptor binding, create more selective agonists or antagonists, and improve cellular transport.
Available non-natural amino acids include D-amino acids, N-methyl amino acids, alpha-methyl amino acids, beta-homo-amino acids, and more than 700 unusual amino acids found in nature, each offering specific functional advantages for peptide design.
Unusual amino acids can modify the hydrophobicity and charge of peptides, improving their ability to cross cell membranes and increasing the efficiency of drug delivery to target cells.
Yes, by strategically incorporating unusual amino acids, peptides can be tailored to target specific biological functions such as enzyme inhibition, metal chelation, or neurotoxicity, offering significant potential for drug discovery and development.
References
