Designed peptides: Candidates for the treatment of cancer, sexual dysfunction, eating disorders

Chemists at the University of Arizona have developed modified versions of naturally occurring peptide hormones that could be key to novel treatments of a variety of diseases, including eating disorders (anorexia, obesity), diabetes, sexual dysfunction and skin cancer.

Victor Hruby, who is a Regents' Professor at the department of chemistry in UA's College of Science and a member of the Drug Discovery Initiative at UA's BIO5 Institute, will talk about the biological roles of peptide hormones and possible applications for designed peptides at the 230th American Chemical Society National Meeting in Washington, DC, on Aug 31, 2005.

Melanotropins are peptide hormones produced in different parts of the body. They play key roles in regulating many biological functions, e.g. eating behavior and metabolism, stress reactions, skin pigmentation and sexual behavior. In the body, melanotropins exert their various functions by binding to specific cellular receptor molecules called melanocortin receptors. To date, scientists have identified five melanocortin receptors (named MC1R through MC5R), all of which differ slightly from each other regarding chemical structure, binding affinity for certain peptides and biological function.

The UA team, led by Hruby, has figured out ways to modify these molecules in the laboratory so they offer improved properties over their natural counterparts. Melanotropins in the body tend to degrade quickly and have overlapping binding specifities (i.e. they bind to different melanocortin receptors). Typically, a given type of melanocortin receptor has a preference for a certain melanotropin, but it can bind to various others, playing a major role in a biological function and a participating role in others.

"We discovered that if we alter the chemical structure of the ligands in a slight but very precise way, they become 100 times more selective or 100 times more potent," said Hruby.

In contrast to the melan

Contact: Daniel Stolte
University of Arizona

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