Designer peptides provide treatment

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

Melanotropins are peptide hormones produced in different parts of the body. They play key roles in regulating many biological functions, such as eating behavior and metabolism, stress reactions, skin pigmentation, and sexual behavior. In the body, melanotropins exert their various functions by binding to specific 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 Arizona team, led by professor of chemistry Victor 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 usually degrade quickly and have overlapping binding specialties (i.e., they adhere to different melanocortin receptors). Typically, a given type of melanocortin receptor has a preference for a specific melanotropin, but it can stick to others as well, 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 manner, they become 100 times more selective or 100 times more potent," Hruby notes.

In contrast to the melanotropins occurring in the body, which tend to degrade quickly, sometimes within seconds, the artificial ligands are more stable. This is a crucial prerequisite for any drug that is administered peripherally and then travels through the intestinal tract or the bloodstream.

Scientists hope that melanotropin-based medicine can overcome certain disadvantages of drugs that currently are available. "Patients would have to take less amounts of a melanotropin-based drug and experience fewer side effects," Hruby contends.

Hruby's team also managed to modify ligands so that they can cross the blood-brain barrier--an obstacle that prevents most substances circulating in the bloodstream from trespassing into the brain tissue.

Ligands developed by the scientists include a host of promising drug candidates. Some could be used to dampen appetite, others to restore erectile function, and still others have been shown to promote tanning of the skin.

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