Peptidomimetics are synthetic small molecules engineered to replicate the structure and function of peptides. While peptides offer advantages like superior binding affinity, selectivity, and low toxicity, their limited bioavailability, metabolic stability, and high cost hinder their representation in the pharmaceutical market. Peptidomimetics, truncated versions of peptides retaining minimum active sequences (MAS), emerge from detailed structure-activity relationship (SAR) exploration, including changes to backbone structures, side-chain modifications, use of unnatural amino acids or incorporation of non-peptide elements. This process transforms the bioactive sequence into a more drug-like compound, making them valuable in drug design and development. Approved peptidomimetic drugs, such as Nirmatrelvir, Bortezomib, Ximelagatran, Atazanavir, and Saquinavir, exhibit properties akin to small molecule drugs, including oral bioavailability, cell penetration, and favorable pharmacokinetics (PK). With advancements in technology and structure elucidation (e.g., AI, CADD), peptidomimetics are garnering increased attention from academia and industry, potentially unlocking a wide array of drug targets. The future holds promise for deriving more peptidomimetic drugs from peptides, as peptide therapy is projected to grow at a compound annual growth rate (CAGR) of 10% from 2023 to 2032.

As peptidomimetics typically stem from peptides, the structures and properties of the starting peptides are essential for successful conversion into peptidomimetics. mRNA display stands out as a revolutionary method for discovering peptide hits. PeptiFinder Biotech provides top-tier mRNA display-centered platform services, boasting trillion diversity libraries (linear, mono-cyclic, and bi-cyclic), can identify potent peptide binders (hits) for your specific targets in a month. Additionally, PeptiFinder can also design and screen customized libraries up to 10^15 tailored to your specific needs. Meanwhile, DEL screening guided by the mRNA display hits and ligand-protein interaction model assures of targeting the appropriate pool of compounds. This facilitates the rapid identification of potent peptide binders for specific targets, incorporating unnatural amino acids to tailor physiochemical properties and expedite the Hit-to-Lead process.

Current Medicinal Chemistry, 2013, 20, 3803-3817

Journal of Medicinal Chemistry 2022 65 (15), 10655-10673

Exploiting Chemical Diversity for Drug Discovery