Abstract: Methods for modulating the hypocretin system, as well as methods for identifying compounds that act as hypocretin-system modulators are provided. In modulating the hypocretin system, the method comprises administering a therapeutically effective amount of a preprohypocretin-expression modulator to an individual, wherein the preprohypocretin-expression modulator alters preprohypocretin expression in preprohypocretin-expressing cells. The method for identifying compounds comprises contacting a test compound to cells equipped with the 5′ flanking promoter of the preprohypocretin gene operably linked to a nucleic acid sequence and determining whether the test compound alters transcription of the nucleic acid sequence in the cell, wherein the test compound's ability to alter transcription is indicative of a compound that modulates the hypocretin system.

Abstract: Methods for modulating the hypocretin system, as well as methods for identifying compounds that act as hypocretin-system modulators are provided. In modulating the hypocretin system, the method comprises administering a therapeutically effective amount of a preprohypocretin-expression modulator to an individual, wherein the preprohypocretin-expression modulator alters preprohypocretin expression in preprohypocretin-expressing cells. The method for identifying compounds comprises contacting a test compound to cells equipped with the 5′ flanking promoter of the preprohypocretin gene operably linked to a nucleic acid sequence and determining whether the test compound alters transcription of the nucleic acid sequence in the cell, wherein the test compound's ability to alter transcription is indicative of a compound that modulates the hypocretin system.

Abstract: A method for obtaining heterologous peptides from fusion proteins wherein at least one of the fusion components is connective tissue-activating peptide-III is provided. Hirudin, a laminin B.sub.1 peptide and platelet factor 4 are polypeptides expressed using this method. DNA sequences encoding the fusion protein, vectors containing these sequences and transformed prokaryotic hosts useful in practicing the method of the present invention are also provided.

Abstract: A synthetic structural gene encoding CTAP-III or CTAP-III-Leu21 including adaptors for the carboxy and amino terminal ends of the gene which contain start and stop codons and convenient restriction sites for use in cloning the gene is described. The gene was designed for efficient expression in bacteria and to include two unique restriction sites for BamHI and XbaI. Plasmid expression vectors that are derivatives of pBR322 that contain a ColE1 insert which includes the expression control sequence and structural gene for colicin are also described. Constructs for expressing CTAP-III, CTAP-III-Leu21, CTAP-III or CTAP-III-Leu21 having a nonpolar pentapeptide fused to its amino terminus, and fusion proteins of such CTAP-III proteins and a colicin fragment are prepared by inserting the synthetic structural gene into the vectors at positions in phase with the colicin expression control sequence and under the control thereof.