PEPTIDE AGONISTS OF GLP-1 ACTIVITY

1 . A peptide conjugate comprising a peptide X selected from the group consisting of (a) an exendin having at least 90% homology to exendin-4; (b) a variant of said exendin wherein said variant comprises a modification selected from the group consisting of between one and five deletions at positions 34-39 and contains a Lys at position 40 having a lipophilic substituent; or (c) GLP-1 (7-36) (SEQ ID NO: 114) or GLP-1 (7-37) (SEQ ID NO: 123) having at least one modification selected from the group consisting of: (i) substitution of D-alanine, glycine or alpha-amino isobutyric acid for alanine at position 8 and (ii) a lipophilic substituent; and Z, a peptide sequence of 4-20.amino acid units covalently bound to said variant, wherein each amino acid unit in said peptide sequence, Z is selected from the group consisting of Ala, Leu, Ser, Thr, Tyr, Asn, Gin, Asp, Glu, Lys, Arg, His, Met, Orn, and amino acid units of the general formula I —NH—C(R 1 )(R 2 )—C(═O)-(1) wherein R 1 and R 2 are selected from the group consisting of hydrogen, C 1-6 -alkyl, phenyl, and phenyl-methyl, wherein C 1-6 -alkyl is optionally substituted with from one to three substituents selected from halogen, hydroxy, amino, cyano, nitro, sulfono, and carboxy, and phenyl and phenyl-methyl is optionally substituted with from one to three substituents selected from C 1-6 -alkyl, C 2-6 -alkenyl, halogen, hydroxy, amino, cyano, nitro, sulfono, and carboxy, or R 1 and R 2 together with the carbon atom to which they are bound form a cyclopentyl, cyclohexyl, or cycloheptyl ring, e.g. 2,4-diaminobutanoic acid and 2,3-diaminopropanoic acid; and a pharmaceutically acceptable salt or the c-terminal amide of said peptide conjugate, with the proviso that x is not exendin-4 or exendin-3.

2 - 48 . (canceled)