Supercomputer-designed hypertension drug mimics natural hormone response

A pharmacophore model of the catestatin-mimicking hypertension drug--Courtesy of UCSD

A new supercomputer drug design that mimics a naturally occurring human peptide may help keep hypertension at bay by controlling the release of hormones that shut down stress-related signaling pathways.

Researchers at the University of California in San Diego have developed a compound, TKO-10-18, that acts much the way the natural peptide catestatin does, binding nicotinic acetylcholine receptors in the nervous system, controlling the release of hormones, called catecholamines, during times of stress, according to the university. By studying catestatin and matching 3-D compound structures to meet its fingerprint, the team synthesized a compound capable of lowering hormone levels in live cells, as published in the journal Bioorganic & Medicinal Chemistry.

The design of the new drug gives it unique capabilities: High-performance computers at the university's San Diego Supercomputer Center allowed the researchers to create a compound with similar physical characteristics to catestatin, including delivery features and active binding centers. TKO-10-18 was one of 7 compounds the team tested out of about 250,000 compounds in the Open NCI Database screened by the computer for a matching 3-D structure.

"Analysis of the catestatin molecule yielded a family of small organic compounds with preserved potency and pathway specificity," coauthor Valentina Kouznetsova said in a statement. "Further refinement of our model should lead to a synthesis and development of a novel class of antihypertensive agents."

Hypertension affects about 76 million people in the United States, according to the American Heart Association, and can lead to blood vessel damage, kidney failure, heart attack and stroke if left untreated.

"Our results suggest that analogs can be designed to match the action of catestatin, which the body uses to regulate blood pressure," said lead author Daniel O'Connor. "Those designer analogs could ultimately be used for treatment of hypertension or autonomic dysfuction."

- here's the UCSD report