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Incorporating non-standard amino acids

In addition to the 20 natural L-amino acids, there are many unnatural or non-canonical amino acids that can be incorporated into the sequence of chemically synthesized peptides. There are many different reasons for including unnatural amino acids, for example, such as increasing the affinity, selectivity, and stability of peptide drugs. Another application is the use of unnatural amino acids to induce or stabilize secondary structures (α-helices, β-sheets).

OOO IQ Chemical offers the synthesis of peptides containing a wide variety of non-canonical amino acids in their structure. These include D-amino acids, homoamino acids, beta-homoamino acids, N-methylamino acids, alpha-methylamino acids, amino acids with unnatural side chain variants, and other non-canonical amino acids.

D-amino acids are the mirror image of naturally occurring L-isomers. They are used for various purposes, mainly to increase proteolytic resistance. Therefore, peptides containing D-amino acids are significantly more stable than peptides containing only L-amino acids. In some cases, peptides containing D-amino acids exhibit increased biological activity compared to their natural L-variants.

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Homoamino acids The prefix "homo" to the name of an amino acid signifies the addition of a methylene (-CH2-) group to the α-carbon atom of the amino acid. They are used to create peptides that may have altered biological characteristics, such as increased biological activity and/or stability.

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Beta-homoamino acids are analogues of standard amino acids in which the carbon skeleton is extended by including one carbon atom immediately after the acid group. The inclusion of beta-homoamino acids in bioactive peptides can improve their pharmacological properties. An increase in half-life in vivo is a known effect of beta-homoamino acid inclusion. Beta-homoamino acids can enhance the efficacy, enhance selectivity, and reduce toxicity of peptide drugs.

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N-methylamino acids are amino acids that carry a methyl group with its nitrogen rather than proton. The addition of an N-methylamino acid generally increases the enzymatic stability of the peptide, thereby increasing its biological half-life. 

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Alpha methyl amino acids are another type of natural amino acid variant in which the proton of the carbon atom (between the amino and carboxyl group) is replaced by a methyl group. As a result, alpha-methyl amino acids are completely resistant to racemization/epimerization, given that there is no longer the possibility of abstraction of the alpha proton. In addition, alpha-methyl amino acids increase the resistance of the peptide to proteolytic degradation.

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Non-canonical amino acids are most often found in bacterial peptides and proteins and are formed through post-translational modifications. Non-canonical amino acids determine the special biological function of these peptides. 

Prominent examples are: citrulline (Cit), hydroxyproline (Hyp), norleucine (Nle), 3-nitrotyrosine, nitroarginine, ornithine (Orn), naphthylalanine (Nal), Abu, DAB, methionine sulfoxide, and methionine sulfone. In the development of peptide drugs, non-canonical amino acids can be used to enhance the pharmacological activity of the peptide drug.

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