Peptide Backbone Modification Service

Some peptides require additional modifications to better mimic the native peptide or protein fragments they are modeled on. These modifications not only enhance peptide stability and bioactivity but also confer higher specificity and targeting. CD ComputaBio's peptide backbone modification services meet diverse client needs, facilitating the advancement of research and related applications.

Introduction to Peptide Backbone Modification

Peptide backbone modification allows an outstanding fine-tuning of peptide conformation, folding ability, and physico-chemical and biological properties.There are diverse methods for peptide backbone modification, including substituting L-amino acids with D-amino acids, inserting methyl-amino acids, and introducing β-amino acids and peptoids. For instance, introducing these non-natural amino acids into the peptide sequence, especially at proteolytic sites, can improve the proteolytic stability of peptides, which is an effective strategy for prolonging the plasma half-life of peptide drugs.

Fig. 1 Peptides versus small molecules and biologics. Fig. 2 Backbone N-methylation of peptides. (Li X, et al., 2023)

Backbone Modification of Peptide Drugs

Rezafungin

The cyclization modification of rezafungin, an echinocandin peptide analog used to treat candidemia and invasive candidiasis, not only eliminates the amino and carboxyl groups at the N- and C-termini of peptides, which are susceptible to degradation by exopeptidases, but also maintains the peptide conformation in a state conducive to receptor binding, thereby enhancing its biological activity.

Cyclosporine A

Cyclosporine A, an approved peptide drug, contains seven N-methyl amino acids in its structure, which greatly improves its hydrolytic stability, making it the first peptide drug to achieve oral delivery.

Our Services

Leveraging advanced computational biology tools and technologies, such as molecular dynamics simulations and artificial intelligence predictions, CD ComputaBio provides peptide backbone modification services, ensuring that modified peptides maintain or enhance their original functions while exhibiting improved performance.

Fig. 2 CD ComputaBio's peptide backbone modification protocol.

Common Strategies for Peptide Backbone Modification

N-terminal Modification

Introducing acetylation or hydrophobic groups at the N-terminus of the peptide chain shields the exposed amino group, reducing protease degradation and enhancing membrane permeability.

C-terminal Modification

Performing amidation at the C-terminus reduces the chemical activity of the carboxylic acid end, prolonging the in vivo half-life.

Splicing Strategy

Combining advantageous peptide segments through splicing rapidly yields compounds with higher activity.

Cyclization Strategy

Closing the peptide chain through disulfide or amide bonds restricts conformational freedom, enhancing target binding affinity and metabolic stability.

Non-natural Amino Acid Modification

Replacing with D-amino acids, β-amino acids, or methyl-amino acids disrupts enzyme cleavage sites and enhances resistance to hydrolysis.

Pseudopeptide Strategy

Utilizing bioisosteric replacement to substitute easily hydrolyzed amide bonds, protecting the peptide from proteolytic cleavage.

Peptide drugs face challenges in clinical applications due to their inherent instability and susceptibility to degradation. CD ComputaBio offers comprehensive peptide backbone modification services to provide insightful perspectives and solutions for your peptide drug development. We look forward to collaborating with you, please contact us with any needs.

References:

Li, X.; et al. Backbone N-methylation of peptides: Advances in synthesis and applications in pharmaceutical drug development[J]. Bioorganic Chemistry. 2023, 141: 106892.
Wang, L.; et al. Therapeutic peptides: current applications and future directions[J]. Signal transduction and targeted therapy. 2022, 7(1): 48.
Boto, A.; et al. Site-selective modification of peptide backbones[J]. Organic Chemistry Frontiers. 2021, 8(23): 6720-6759.

For research use only. Not intended for any clinical use.

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