Unusual & Non-natural Amino Acids Modified Peptide Synthesis

In addition to the 20 natural L-amino acids, there are a large number of unnatural or unusual amino acids that can be built into synthetic peptides to enhance affinity and selectivity for peptide drug lead stability or to induce or stabilize secondary structure (α-helix, β-sheet, β-turn). CD Formulation offers a large number of unnatural or unusual amino acids that we routinely incorporate into peptides. These include D-amino acids, β-homo-amino acids, N-methyl amino acids, α-methyl amino acids, unnatural side chain variant amino acids, and other unusual amino acids.

Advantages of Unusual & Unnatural Amino Acid Modifications

Unnatural amino acids, also known as non-protein amino acids, are artificially synthesized. More than 200 such molecules have been utilized. Since unnatural amino acids are not present in proteins, enzymes cannot recognize them as cleavage sites for proteolytic degradation. Therefore, unnatural amino acids can be incorporated into customized peptides for various applications, such as pharmacologically active ingredients, various structural combinations, and strong molecular scaffolds.

Modified peptides containing unnatural amino acids have the following functions:

• High selectivity.
• High cell membrane permeability.
• Longer in vivo half-life.
• Improved receptor binding.
• Modified activity as an agonist or antagonist.

Fig. 1 Different strategies of non-proteogenic amino acids incorporation to improve the pharmacokinetic properties of peptide drugs. (Ding Y, et al., 2020)

Explore Our Custom Unusual & Non-natural Amino Acids Modified Peptide Synthesis Services

As an expert in peptide modification, CD Formulation provides unparalleled unusual & non-natural amino acids peptide modification services to customers around the world. We have reliable synthesis procedures and excellent peptide analysis technology to solve any possible challenges in developing and producing peptide therapeutics.

Over the years, our peptide synthesis experts have built a rich library of unnatural amino acids, which can be used to design peptide or protein therapeutics with desired biological activity and physicochemical properties.

The following are the unusual and non-natural amino acid modification options that CD Formulation can provide:

D-Amino Acid

D-amino acids, a class of isomers of amino acids, are mirror-symmetrical in molecular structure to L-amino acids (usually the common form of amino acids in organisms). Peptides containing D-amino acids are significantly more stable than peptides containing only L-amino acids. In some cases, peptides containing D-amino acids show higher biological activity than their natural L-variants.

Homoamino Acid

The introduction of homologous amino acids can be used to create peptides that may have altered biological properties, such as better physicochemical properties, enhanced biological activity, and biological stability. Common homologous amino acids include alanine (Ala), isoleucine (Ile), and glutamic acid (GLU).

β-Homoamino Acid

A class of standard amino acid analogs characterized by the amino group (-NH2) being located at the β position of the carbon chain, as opposed to the common α-amino acids, where the amino group is located at the α position of the carbon chain. The carbon backbone of this type of amino acid is lengthened by inserting a carbon atom immediately after the acid group.

The incorporation of β-homoamino acids into bioactive peptides can improve their pharmacological properties, such as extending half-life, increasing bioactivity and selectivity, and reducing toxicity.

N-Methyl Amino Acid

N-methyl amino acids are a special class of amino acids, in which one or more of the hydrogens of the amino group are replaced by a methyl group (-CH3). These amino acids generally have biological activities different from those of natural amino acids and can improve the pharmaceutical properties of bioactive peptides. The introduction of N-methyl amino acids generally increases the enzymatic stability of peptides, prolongs the biological half-life, and enhances intestinal permeability.

α-Methyl Amino Acid

α-Methyl amino acids, a natural amino acid variant, are characterized by a methyl (-CH₃) substituent on the α-carbon atom. This structure makes them particularly useful in biochemistry and medicinal chemistry, especially to increase the proteolytic stability of peptides. This is because α-methyl amino acids are completely stable to racemization/epimerization and no longer have the possibility of abstracting the α-proton.

Unusual Amino Acid

Unusual amino acids are usually formed post-translationally under specific circumstances or in specific organisms. These amino acids contribute to the improvement of specific biological activities of peptides. In peptide therapeutic development, unusual amino acids are used to enhance the pharmaceutical properties of peptide drug leads.

The following are the unusual amino acid options that CD Formulation can provide:

Citrulline (Cit)		Pyroglutamic Acid (Pyr)
Naphthylalanine (Nal)		Abu (α-aminobutyric acid)
Ornithine (Orn)		DAB (2,4-diaminobutyric acid)
Norleucine (Nle)		Nitroarginine
Nitrotyrosine (NT)		Methionine Sulfoxide
Hydroxyproline (Hyp)		β-alanine

Peptide Manufacturing & Analytical Services

In addition to peptide synthesis capabilities, CD Formulation combines flexible GMP manufacturing facilities with cutting-edge peptide analytical knowledge to provide a full range of quality control testing services to accelerate the commercialization of your products, including:

Publication

CD Formulation has extensive experience with every modification of peptides. Please don't hesitate to contact us if you are interested in our services, and to learn more about the possibilities of incorporating unusual and non-natural amino acids into your peptides. We look forward to cooperating with you.

How It Works

STEP 1

Submit a service request describing your specific research or development need.

STEP 2

We'll email you to provide your quote and confirm order details if applicable.

STEP 3

Execute the project with real-time communication, and deliver the final report promptly.