Maximize the diversity of your random peptide libraries without compromising on quality. Whether you are working in epitope mapping, drug discovery, or vaccine development, ProteoGenix’s platform will help you get the peptide library best adapted to your unique challenges and needs.

How to design random peptide libraries

Combinatorial libraries, such as random peptide libraries, are designed to enhance specific physicochemical properties, interrogate certain protein-protein interactions, or discover novel bioactive peptides. These libraries are generated by substituting selected residues within a segment with each of the 20 natural amino acids.

The higher the number of selected residues to be randomized, the larger the library. However, unlike other combinatorial library designs, vast libraries do not always translate into better experiments. 

Randomizing several residues at once may have the potential to generate binders with new and promising activities. Nevertheless, if the purpose of the experiment is to improve selectivity, specificity, or protein stability, it is advisable to restrict the number of sites submitted to randomization to better assess the impacts of each mutation on the peptide’s bioactivity.

In addition, the vaster the random peptide library, the more challenging it is to screen it. To overcome this limitation, researchers recurrently group several random peptides into a restricted number of peptide pools. Once a bioactive pool is identified, individual peptides that comprise that pool are selected for further screening and development.

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Applications of random peptide libraries

Random peptide libraries have the highest potential for sequence diversity. For this reason, this type of combinatorial design is often employed in drug discovery and vaccine development.

Due to their small size, peptide drugs are prized for their target specificity and unique properties. Unlike larger macromolecules such as antibodies or enzymes, peptides can fit into conventionally inaccessible binding sites and easily cross physical barriers such as membranes. In addition, peptides are quickly broken down into amino acids by the organism, significantly limiting their toxicity.

As biotherapeutics, peptide drugs have vast applicability in treating metabolic, cancer, and cardiovascular diseases.

Before the 2000s, the discovery of peptide drugs focused on generating hormone mimics composed simply of natural amino acids. With the advent of the 21st century and the advancement of peptide library synthesis platforms, this field has taken a new turn.

Today, peptide drug discovery is recurrently carried out using proteins of viral or bacterial origin as the basis for designing randomized libraries. These libraries, often comprised of unnatural or modified amino acids, allow the identification of novel bioactive peptides devoid of toxicity.

In vaccine development, random peptide libraries recurrently help identify epitopes on specific antigens. Conventional peptide vaccines (single epitope) or multi-epitope peptide vaccines are historically cheaper and quicker to manufacture.

The success of these vaccines depends on how well the peptide ligand can act as an immunogen and mimic the in vivo antibody response elicited by the native antigen. Numerous studies have reported the successful use of random peptide libraries for the discovery of immunogenic mimics, indicating the value of this approach for peptide vaccine development.

These combinatorial libraries have also proven helpful for epitope discovery, particularly when the antigen is unknown. Studies using panels of human sera, often containing high concentrations of oligoclonal antibodies, have previously identified critical epitopes in emerging infectious and autoimmune diseases when little to no information was available.

Besides providing the basis for further drug development, these epitopes can be repurposed into fast, specific, and inexpensive diagnostic tools.

Reach out to our team of experts and learn how we can work together to expedite your random peptide library generation project: