Marine and coastal organisms: a source of biomedically relevant dipeptidyl peptidase IV inhibitors

Dipeptidyl peptidase IV (DPP-IV, EC 3.4.14.5), also known as CD26, is a serine aminopeptidase that preferentially cleaves Xaa-Pro or Xaa-Ala dipeptides from the N-terminus of peptides leading to their biological activation or inactivation. The enzyme is an homodimer and each subunit is formed by an αβ-hydrolase domain and a β-propeller domain. It has an important role in multiple physiological functions, including the regulation of glucose metabolism, being one of the current targets for the treatment of type 2 diabetes mellitus. It is also up-regulated in rheumatoid arthritis, psoriasis, colitis, multiple sclerosis and transplant rejection. This enzyme also regulates immune system responses mediated by CD4+ T lymphocytes; furthermore, DPP-IV activity is dysregulated in pathologies like thyroid, ovarian, lung, skin, prostate cancers and central nervous system tumors. In clinical practice, DPP-IV inhibitors have several beneficial effects such as anti-hyperglycemia and pancreatic islet protection, immune regulation, cardiovascular and renal protection, anticancer effects, and anti-inflammation. Thus, this enzyme evolved as a target of attention for the development of more efficient pathology diagnostics, and for the development of inhibitors to treat type 2 diabetes mellitus and cancer. Marine and coastal organisms are an abundant source of different bioactive molecules including peptidases and peptidases inhibitors of almost all mechanistic classes, being serine class the most studied. In the present contribution, we review the strategies used to identify and characterize DPP-IV inhibitors from marine and coastal organisms. We show that marine biodiversity is an important, promising, and still unexplored source of inhibitors of dipeptidyl peptidase IV, which may have biomedical applications in human diseases.