What Are Constrained Peptides and How Do They Work?

TL;DR

Constrained peptides are small proteins with unique chemical bonds that enhance their stability and potency, allowing them to be used as a new type of medicine. They can be designed from scratch using open-source software, and early trials show promise in treating influenza, botulism, and cancer. These peptides combine benefits of small-molecule and biologic drugs while minimizing side effects.

Transcript

I'm a protein designer. And I'd like to discuss a new type of medicine. It's made from a molecule called a constrained peptide. There are only a few constrained peptide drugs available today, but there are a lot that will hit the market in the coming decade. Let's explore what these new medicines are made of, how they're different and what's causin... Read More

Key Insights

• 💊 Constrained peptides are small proteins with extra chemical bonds that make them stable and potent. They occur naturally in our bodies and in venomous animals.
• 💉 Biologic drugs, including constrained peptides, are advantageous because they are made of natural, nontoxic materials and have fewer side effects compared to small molecule drugs.
• 🔑 Constrained peptides are durable like small molecule drugs but have the benefits of biologic drugs. They can be administered through pills, inhalers, or ointments.
• 🧪 Reengineering constrained peptides from nature to create new drugs is challenging. However, a collaborative effort across institutions developed open-source peptide-design software to build new constrained peptides from scratch.
• 🛠️ The software achieved precision in positioning individual atoms, allowing for custom-tailored shapes of designer peptides for drug development.
• 🌡️ Designed constrained peptides have shown promising results in neutralizing influenza, protecting against botulism poisoning, and blocking cancer cell growth in preclinical trials with laboratory animals.
• ️ Human trials for these designer peptides are still three to five years away, but more constrained peptide drugs are expected to enter the drug development pipeline in the meantime.
• 🌍 Ultimately, designed peptide drugs have the potential to free us from the constraints of diseases, offering a breakthrough in medicine.

Questions & Answers

Q: What are constrained peptides made of and how are they different from regular drugs?

Constrained peptides are small proteins with extra chemical bonds that give them a stable and potent structure. Unlike regular drugs, which are usually small molecules, constrained peptides are larger and have a more complex shape. This makes them highly specific in their interaction with target molecules in the body, resembling a lock and key mechanism. Additionally, constrained peptides are more durable than most biologic drugs, allowing for different administration routes such as pills or ointments.

Q: What advantages do biologic drugs, including constrained peptides, have over regular drugs?

Biologic drugs, such as constrained peptides, have several advantages over regular drugs. Firstly, proteins are naturally occurring and non-toxic to the body, making them a safer option. Secondly, biologics interact with specific molecules in the body, reducing the risk of interacting with unintended targets. Compared to regular drugs, biologics are larger and tend to have fewer side effects. However, one of the drawbacks of most biologics is their fragility, requiring administration through injection rather than oral consumption.

Q: Why is it challenging to reengineer constrained peptides found in nature for drug development?

Reengineering naturally occurring constrained peptides to create new drugs is a difficult task. The shape of constrained peptides is crucial to their function, and any significant change in shape can cause the molecule to fall apart. This poses a challenge when trying to modify the peptides to enhance their therapeutic properties. The need for control over the shape of constrained peptides led to the development of new methods to design peptides from scratch, rather than relying solely on natural peptides.

Q: How did the scientists solve the problem of designing constrained peptides from scratch?

A collaborative effort involving numerous institutions across three continents led to a breakthrough in designing constrained peptides from scratch. Instead of modifying natural constrained peptides, the scientists developed open-source peptide-design software. This software enabled them to generate a series of peptides with a wide range of shapes, including ones never seen in nature. These designed peptides were then synthesized and their molecular structures determined through experiments. Comparing the designed models with actual molecular structures demonstrated the accuracy and effectiveness of the software in designing custom-tailored peptides.

Q: What potential medical applications have been explored with designed constrained peptides?

Designed constrained peptides have shown promising results in various medical applications. Some of these peptides have been specifically designed to neutralize influenza viruses, protect against botulism poisoning, and inhibit the growth of cancer cells. In preclinical trials with laboratory animals, these new drugs have demonstrated both safety and high effectiveness. However, it is important to note that the drug development pipeline is slow and cautious, so it will be several years before these designed peptides can enter human trials. Nonetheless, the technology holds great potential for breaking free from the constraints of diseases.

Summary & Key Takeaways

• Constrained peptides are small proteins with extra chemical bonds that make them stable and potent, and they are naturally occurring in our bodies and in venomous animals.

• Biologic drugs, including constrained peptides, have advantages over small molecule drugs because they are made of natural materials and have fewer side effects.

• Constrained peptides are durable and can be administered through pills, inhalers, and ointments, making them desirable for drug development, but reengineering them is difficult. However, a team of scientists has developed a method to design new constrained peptides from scratch using freely available software. These designed peptides have shown promise in neutralizing influenza, protecting against botulism, and blocking cancer cells.