Compositions and methods for promoting lipid mobilization in humans

A method of promoting lipid mobilization in a human, the method comprising administering to the human a nucleic acid expression vector comprising a nucleic acid encoding a polypeptide having the chemical structure

• 21 Xaa0 - Xaa2 - Xaa3 - Xaa4 - Xaa5 - Xaa6 - Xaa7 - Xaa8 - X,
• wherein:
• Xaa0 is one of a glutamate residue and a glutamine residue;
• Xaa2 is one of a leucine residue, an isoleucine residue, a valine residue, a phenylalanine residue, and a tyrosine residue;
• Xaa3 is one of an asparagine residue and a threonine residue;
• Xaa4 is one of a phenylalanine residue and a tyrosine residue;
• Xaa5 is one of a threonine residue and a serine residue;
• Xaa6 is one of a proline residue, a serine residue, a threonine residue, and an alanine residue;
• Xaa7 is one of glycine residue, an asparagine residue, a serine residue, an aspartate residue, a valine residue, and a tryptophan residue;
• Xaa8 is a tryptophan residue;
• and
• X is from 0 to 10 amino acid residues.

A method of making a pharmaceutical composition for promoting lipid mobilization in a human, the method comprising

• i) cyclizing the amino-terminal amino acid residue of a polypeptide having the chemical structure
• 22 Xaa0 - Xaa2 - Xaa3 - Xaa4 - Xaa5 - Xaa6 - Xaa7 - Xaa8 - X,
• wherein:
• Xaa0 is one of a glutamate residue and a glutamine residue;
• Xaa2 is one of a leucine residue, an isoleucine residue, a valine residue, a phenylalanine residue, and a tyrosine residue;
• Xaa3 is one of an asparagine residue and a threonine residue;
• Xaa4 is one of a phenylalanine residue and a tyrosine residue;
• Xaa5 is one of a threonine residue and a serine residue;
• Xaa6 is one of a proline residue, a serine residue, a threonine residue, and an alanine residue;
• Xaa7 is one of glycine residue, an asparagine residue, a serine residue, an aspartate residue, a valine residue, and a tryptophan residue;
• Xaa8 is a tryptophan residue;
• and
• X is from 0 to 10 amino acid residues
• so that the polypeptide has a pyroglutamate residue at its amino terminus;
• and
• ii) combining the polypeptide with a pharmaceutically acceptable carrier.

A method of identifying an agent effective for promoting lipolysis in humans, the method comprising

• i) derivatizing a compound having the chemical structure
• 23 Xaa1 - Xaa2 - Xaa3 - Xaa4 - Xaa5 - Xaa6 - Xaa7 - Xaa8 - X - Z,
• wherein:
• Xaa1 is a pyroglutamate residue;
• Xaa2 is one of a leucine residue, an isoleucine residue, a valine residue, a phenylalanine residue, and a tyrosine residue;
• Xaa3 is one of an asparagine residue and a threonine residue;
• Xaa4 is one of a phenylalanine residue and a tyrosine residue;
• Xaa5 is one of a threonine residue and a serine residue;
• Xaa6 is one of a proline residue, a serine residue, a threonine residue, and an alanine residue;
• Xaa7 is one of glycine residue, an asparagine residue, a serine residue, an aspartate residue, a valine residue, and a tryptophan residue;
• Xaa8 is a tryptophan residue;
• X is from 0 to 10 amino acid residues;
• and
• Z is one of a hydrogen radical and a carboxyl terminus-blocking moiety to form a polypeptide derivative;
• and
• ii) assessing the ability of the derivative to mobilize lipids, whereby ability of the derivative to mobilize lipids is an indication that the derivative is an agent effective for promoting lipolysis in humans.