A Basic Guide to Stapled Peptides: What You Need to Know

Peptides are short chains of amino acids linked together by peptide bonds. Peptides are responsible for fighting bacteria, wound healing, and muscle growth, carrying biological messages from tissue to the blood and back again. They also play many other key roles in the body.

But what are stapled peptides? You’ve likely heard of these before, whether in a pharmacologic sense or in passing.


Stapled peptides are peptide chains with an external brace, forcing the peptide structure into an 𝛼-helical one, as stated by a 2019 study. Peptides are locked into a conformation to reduce conformational entropy. Using this process can help increase cell penetration and increase target affinity, which is essential to protect against proteolytic degradation. 

There are many reasons why we may use stapled peptides as opposed to regular peptides. Mainly though, the smaller molecule design allows for better synthesis. 

So, with this in mind, the remainder of this blog post will discuss more on stapled peptides, including what they are, why we need them, and more.

What are peptides?

Peptides are strings of amino acids, made naturally by the body.

Some peptides are also made in a laboratory, often used for medications to treat diseases including diabetes and multiple sclerosis, among others.

Peptides have even made their way into dietary supplements and other health pills, with peptides such as collagen thought to promote healthy skin, and creatine (a widely used peptide) which is thought to help build muscle.

We also find peptides in foods, including meat, oats, fish, hemp seeds, flaxseeds, and wheat.

What are stapled peptides?

Stapled peptides are small modified helical proteins adjusted to perform one specific job.

The peptide acts like the original protein at the binding site. However, it’s a much smaller molecule in absorption, metabolism, and distribution – i.e., increasing the effectiveness of the peptide and its role in the body, whether that’s in treating disease or something else entirely.

While the resurgence of stapled peptides is a thing of recent years, using these could be promising in treating certain diseases by impairing disease-relevant proteins. Essentially, you’re editing/telling the peptide to do exactly what you want with fewer negative side effects.

The use of these peptides may play a key role in single-agent treatments, paired with other therapeutic modalities, changing the way in which medicine is created to treat disease.

Why do we use stapled peptides?

Chains of amino acids (peptides) are found within the body, playing many different roles such as muscle repair, immune strength, and wound healing. But one of the main disadvantages of regular peptides is their volatility in the physiological environment (your body).

Stapled peptides, on the other hand, are stapled to lock the peptide structure. The locking of the peptide side chains reduces the volatility in the body, allowing it to be used more effectively. 

They can also be used for other uses, introducing other compounds and even delivering a specific drug to a target area of the body, releasing it there for maximum effect and minimum side effects.

And while the use of stapled peptides is still somewhat early, it is an exciting concept – that’s for sure. Not to mention one we’ll certainly be seeing and hearing a lot more about in the next few years.

The potential of stapled peptides is universal and could be evolutionary in the field of medicine and pharmaceuticals, transforming the way we approach curing disease, and perhaps even creating much-needed breakthroughs within the space.

The bottom line 

Stapled peptides are linear peptides that are locked into a helical formation. Locking a peptide into formation makes it less volatile in the body, allowing it to perform a more specific job with better results.

The use of these peptides could be used to provide better treatment for certain diseases, delivering certain drugs to a very specific part of the body. This would reduce side effects and increase the responsiveness of the drugs for better treatment and results.

And while further research and developments are still required, the application of helical formation peptides is exciting, to say the least.

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