Therapeutic peptides have gained increasing interest in drug discovery. Compared to small molecule therapeutics, peptide-based drugs often show more selective receptor binding and thus present with less off-target related adverse effects. In addition, their metabolites (amino acids) have few toxicity concerns. The rise of peptide therapeutics has reshaped the pharmaceutical landscape, as exemplified by the expanding number of human peptide hormone analogues engineered to have extended circulating half-life. To date, more than 100 therapeutic peptides have approved by the U.S. Food and Drug Administration (FDA) and the pipeline of clinically relevant innovative peptide therapeutics is continuously expanding.
Their applicability is wide-ranging and peptide drugs have provided treatment options for diseases which have previously been difficult to treat such as osteoporosis, prostate cancer, growth hormone deficiency, hyperparathyroidism, neuroendocrine tumors, and short bowel syndrome. Remarkably, propelled by major breakthroughs in molecular biology and peptide chemistry, incretin-based peptide therapies have revolutionized obesity and diabetes management, exemplified by semaglutide (glucagon-like peptide-1 (GLP-1) receptor agonist) and tirzepatide (dual GLP-1 and gastric inhibitory polypeptide (GIP) receptor agonist). These compound classes have also demonstrated significant benefits in associated severe metabolic disease complications such as metabolic dysfunction-associated steatohepatitis (MASH), chronic kidney disease (CKD) and cardiovascular disease (CVD), emphasizing the broad applications of these therapeutic peptides.
Innovative Approaches in Peptide Drug Discovery
Modification of natural peptide ligands has for decades been considered the most feasible strategy in peptide drug discovery which, however, has left a narrow space for developing novel peptides that could that carry untapped therapeutic potential. These limitations have prompted the development of various approaches and technologies such as mRNA display that enable identification of de novo peptide ligands with no natural origin.
Artificial Intelligence in Peptide Discovery
The extreme number of possible amino acid combinations in a peptide sequence result in a vast peptide-chemical space to be exploited for potential bioactive compounds. Various in silico hit generating tools have been developed to accelerate development of novel peptide drugs. In this regard, artificial intelligence (AI) based tools, including AlphaFold, have the potential to transform peptide drug discovery by enabling rapid analysis of large-scale data sets with the aim to predict the 3D structure and interactions of a given peptide.
Gubra: Leading the Way in Peptide Drug Discovery
Gubra is a full-service CRO and peptide target/drug discovery partner. We offer expert preclinical research services enabling pharmaceutical and biotech companies to advance their drug development pipeline by employing state-of-the-art techniques to profile drug candidates in a wide array of clinically translatable research models.
streaMLine: Accelerating Discovery
We have developed streaMLine, an innovative platform for peptide drug discovery that greatly shortens the time from initial hit to clinical drug candidate. Our integrated AI-assisted discovery platform enables our multidisciplinary teams to deliver unprecedented rapid and unbiased synthesis and characterization of complex peptides for therapeutic potential. These include both linear and macrocyclic peptides. To learn more, visit Gubra CRO Services and Gubra Discovery.
