Peptide Building Blocks: Frequently Asked Questions

What are peptide building blocks?

Peptide building blocks are the starting materials used to construct peptides. Peptide therapeutics composed of these building blocks can be designed to target specific indications, including metabolic diseases, neurological disorders, and cancer.

Peptide building blocks are typically amino acid derivatives, which is why they are also known as protected amino acids. There are twenty canonical, or natural, amino acids found in the human body, while non-canonical amino acids (ncAAs) are often engineered or modified to enhance stability, functionality, or specificity. ncAAs can be used to help increase the potency and elongate the half-lives of peptide compounds. 

What is the difference between peptides and peptide building blocks?

Peptides are the final molecules—chains of amino acids linked together—while peptide building blocks are the starting materials used to create them. Here at Grace, we focus on manufacturing complex peptide building blocks at our Tyrone, PA facility.

In peptide synthesis, building blocks are carefully assembled step-by-step to form the desired peptide structure, ensuring accuracy and consistency throughout the process. 

Why are peptide building blocks important in the pharmaceutical industry?

Peptide building blocks play a critical role in the development of modern medicines. They are used to create peptide therapeutics that serve as active pharmaceutical ingredients in a wide range of treatments for cancer, obesity, and diabetes. The peptide market is forecasted to exceed $101.7 billion by 2033. 

They are also essential in the production of GLP-1 agonists, including semaglutide and tirzepatide, and other peptide-based drugs that are increasingly important in novel pharmaceuticals, such as those for metabolic health. 

How are peptides synthesized? 

Peptides can be synthesized using one of two methods – either solid-phase synthesis (SPPS) or solution-phase (liquid phase) synthesis (LPPS). Each approach provides different advantages depending on the complexity of the peptide and the desired efficiency of the process. A hybrid approach is commonly used to optimize the outcomes. 

What types of peptide building blocks are used in peptide synthesis? 

A variety of building blocks can be used depending on the peptide design, including standard amino acid derivatives, modified or protected amino acids, and di- and tri-peptides. 

Di-peptide and tri-peptide building blocks are used to improve synthesis efficiency. By incorporating multiple amino acids in a short synthetic sequence, they can streamline workflows and reduce the number of synthesis cycles required. 

How does peptide building block quality impact peptide synthesis?

The quality of peptide building blocks can have a direct impact on final peptide performance. Using high-quality peptide building blocks can enable tighter impurity control (down to 0.1%), improve yield and reproducibility, and reduce downstream purification challenges. Consistent quality is essential for successful peptide production, especially when they are incorporated into pharmaceutical applications.  

What are common challenges in the manufacturing of peptide building blocks?

Challenges in manufacturing peptide building blocks can include filtration issues and impurity control. For instance, the physical properties of the peptide building blocks can sometimes cause issues, including poor filtration properties when isolated. We have a dedicated solid state subject matter expert who helps evaluate the physical properties of the peptide building block in order to manage this challenge. Having the right equipment can also help ensure a smooth manufacturing process. For example, our Tyrone site recently invested in a new Heinkel centrifuge that is more suitable for slow filtering products compared to a Nutsche filter. 

Another challenge is managing impurity control. Any impurities at the peptide building block stage will follow the material through subsequent downstream processes so it is important to minimize impurities at the beginning of the process as much as possible. 

How can artificial intelligence (AI) and machine learning (ML) help improve peptide building block synthesis?  

The possibilities for AI and ML in peptide building block synthesis are exciting! One opportunity is to shorten R&D cycles to help bring therapeutics to market faster. To that end, Grace has a strategic agreement in place with Molecule.one to transform peptide building block synthesis using AI and automation. Through Molecule.one’s MARIA™ Platform for AI and high-throughput experimentation, we can rapidly identify and prioritize novel, efficient production routes for complex building blocks. This can help reduce R&D cycles and speed up progression to the development of a scalable process.

Which peptide building blocks can Grace manufacture in Tyrone, PA?

Grace can support manufacturing for a variety of peptide building blocks, including complex peptide building blocks, at our Tyrone facility. With a long history of manufacturing high-quality regulatory starting materials (RSMs), the site is well-suited to produce complex and hard-to-source protected amino acids. 

What is Grace’s capacity for manufacturing peptide building blocks?

We can produce peptide building blocks at a variety of quantities, including up to metric tons of complex and hard-to-source protected amino acids. With our 2000-4000 gallon (7500-15000L) reactors, we also run commercial-scale production. 

Where does Grace manufacture its peptide building blocks?

Grace’s Tyrone, Pennsylvania, facility combines domestic manufacturing, commercial-scale capacity and deep expertise in complex, hard-to-source peptide building blocks. By partnering with Grace, pharmaceutical manufacturers can strengthen supply continuity, maintain consistent quality and confidently advance peptide therapeutics from development through commercialization.