Stapling is a key technique for stabilising peptides in an α-helical structure. The resultant stapled peptides are then able to compete efficiently for binding to protein targets involved in protein–protein interactions that are mediated by α-helices. Certain general design principles to optimise their binding and biological activity have emerged in recent years. This is accompanied by an increasing use of computational methods in stapled peptide design.

The stapling technique is rapidly emerging as one of the most widely adopted strategies for α-helix stabilisation. Stapled peptides are highly promising therapeutic agents for the inhibition of PPIs, because they generally exhibit enhanced helicity, protease resistance, and biological potency. The development of stapled peptides promises to enable access to α-helix-mediated PPI drug targets. It has also been shown that stapled peptides are able to disrupt enzyme, multidrug resistance efflux pump and membrane receptor dimers, thus opening up new possibilities for targeting traditional drug targets, which is becoming especially important because of the development of resistance against current drugs.

Process of Stapled Peptides
The process of stapling can be achieved using a variety of methods, including ring-closing metathesis (RCM), olefin cross-metathesis (OCM), and hydrogenation. RCM is the most commonly used method, as it is efficient and compatible with a wide range of peptide sequences.

Advantages of Stapled Peptides
Better target affinity
Increased proteolytic resistance and serum half- life
Increased cell permeability
Targeting of either extracellular or intracellular proteins
Non-immunogenicity
Viable pharmacokinetics and in vivo stability
More stable and longer half-life than traditional peptides
Enhanced binding affinity

Available Stapled Peptide Synthesis Services
The synthesis of stapled peptides is different from that of a common peptide. By use of solid phase methods, the peptide chain is introduced two unnatural amino acids containing an α-methyl group and an α-alkenyl group, and then an olefin metathesis reaction occurs between two unnatural amino acids to constitutes a stable α-helical conformation.
One-component stapling techniques: Using non-native amino acids bearing complimentary side-chain functional groups that can be directly coupled together.
Two-component stapling techniques: Involving a bifunctional linker compound which forms a staple by reacting with two complementary non-native amino acids in the peptide of interest.

General Design Principles of Stapled Peptide
Staple position
Staple stereochemistry
Staple length
Multiple staples
Sequence modifications

Characterization of Stapled Peptides
Characterizing stapled peptides is critical for assessing their potency, stability, and pharmacokinetic properties. Here are some common methods we used:
Mass spectrometry
Circular dichroism
Nuclear magnetic resonance
Thermal denaturation
Cell-based assays

Tanda provides efficient and high quality peptide synthesis services while offering different modification services.

Comprehensive expertise
Our team comprises experts in peptide chemistry, molecular biology, bioinformatics, and pharmacology, ensuring a multidisciplinary approach to stampled peptide design.

Cutting-edge technology
We utilize the latest technologies and methodologies to deliver high-quality results.

Customization and flexibility
We offer customizable services tailored to the specific needs of our clients, from small-scale pilot studies to large-scale screening projects, ensuring flexibility and scalability.

Speed and efficiency
Our streamlined processes and integrated workflows enable rapid turnaround times, allowing you to accelerate your drug discovery projects and bring novel therapeutics to market faster.

Quality and reliability
We adhere to stringent quality control measures and industry standards, ensuring the reliability and reproducibility of our results.