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Methylated Peptide Synthesis

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The pharmacokinetic landscape of peptide therapeutics, intriguingly constrained as it is, presents a fascinating puzzle obstructing their apex efficacy across a spectrum of diseases. Enter the compelling strategy of N-methylation—a promising approach aimed at unlocking the latent prowess of these biomolecules. CD Formulation can provide customers with peptide methylation services according to different needs.

What is Methylation?

Methylation is an important translational modification of proteins and peptides. N-methylation is the simplest and smallest modification of a single amino acid or peptide bond. This modification can significantly improve the stability and bioavailability of peptide drug candidates and generate analogs with specific biological activities, such as enzyme inhibitors, receptor antagonists and agonists, as well as building blocks in combinatorial chemistry for screening new potential drugs.

Fig. 1 Peptides backbone N-methylation.Fig. 1 Backbone N-methylation of peptides. (Li X, et al., 2023)

Explore Our Custom Methylated Peptide Synthesis Services

CD Formulation emerges as a luminary in the boundless expanse of peptide synthesis, presenting an extraordinary array of methylated peptide synthesis services tailored for a global clientele.

In our peptide synthesis laboratory, the methylated peptide crafting typically unfolds at the N-terminus of the polypeptide chain. This process intricately weaves together multiple methyl group transfers, artfully targeting the amino acids arginine and lysine, creating a rich tapestry of molecular modifications.

Our extensive services include:

  • Methylated peptide design.
  • Methylated peptide synthesis.
  • Methylated peptide purification.
  • Methylated peptide modification.

Available Methylated Amino Acid Option

Amino Acids Methylated Amino Acids
Lysine Methylation
Arginine Methylation

Our Synthetic Method for Methylated Peptide

Solid-Phase Peptide Synthesis (SPPS)

During the synthesis process, our scientists first construct the peptide chain by coupling different amino acids, and then methylate specific amino acid residues by introducing methylating agents.

Liquid-Phase Peptide Synthesis (LPPS)

Suitable for shorter peptide chains. During the synthesis process, the methylating agent can be directly added to the peptide chain through a chemical reaction under appropriate time and conditions.

Enzymatic Synthesis Method

Methylation of the peptide chain is achieved through the catalytic action of an enzyme. This method usually has high specificity and selectivity, but its scope and conditions of application are limited.

Biosynthesis

Peptides containing methylation sites are synthesized in cells using recombinant technology. This method usually involves genetic engineering technology.

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:

  • Peptide identification (ESI-MS).
  • Peptide Molecular weight determination.
  • Peptide sequencing.
  • Peptide quantification/peptide content determination.
  • Peptide purity and impurity analysis (HPLC/UV).
  • Amino acid sequence.
  • Amino acid composition determination.
  • Net peptide content.
  • Enantiomeric purity testing (GC/MS; LC).
  • Residual counterion testing (e.g. TFA).
  • Elemental analysis.
  • Residual solvent testing.
  • Water content testing (GC or KF).
  • Peptide solubility testing.
  • Peptide stability testing.
  • Optical rotation determination.
  • Bioburden testing(TAMC/TYMC).
  • Bacterial endotoxin testing.
  • Sterility testing.
  • Cytotoxicity testing.
  • Process/product related impurity testing.
  • Other pharmacopoeia testing.

Publication

Published Data

Technology: N-methylation

Journal: Nat Protoc.

IF: 10.032

Published: 2012

Results:

The authors describe two simplified methods for N-methylation of linear peptides on solid supports and two peptide cyclization methods. These N-methylation methods can be completed in less than 2 hours and applied to any amino acid. The peptide cyclization method can be used to obtain N-methylated cyclic peptides, and multiple N-methylated cyclic peptides can be synthesized in just 4-5 days.

Fig. 2 Synthesis of mono/multiply N-methylated cyclic peptide.Fig. 2 Synthesis of mono/multiply N-methylated cyclic peptide on the basis of the Fmoc strategy for peptide synthesis on solid support. (Chatterjee J, et al., 2012)

CD Formulation has extensive experience with each methylation 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 methyl groups into your peptides. We look forward to cooperating with you.

References

  1. Di Gioia ML, Leggio A, Malagrinò F, et al. N-Methylated α-Amino Acids And Peptides: Synthesis And Biological Activity. Mini Rev Med Chem. 2016;16(9):683-90.
  2. Li X, Wang N, Liu Y, et al. Backbone N-methylation of peptides: Advances in synthesis and applications in pharmaceutical drug development. Bioorg Chem. 2023 Dec;141:106892.
  3. Chatterjee J, Laufer B, Kessler H. Synthesis of N-methylated cyclic peptides. Nat Protoc. 2012 Feb 9;7(3):432-44.
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