PTH-COMPOUNDS AND PHARMACEUTICAL COMPOSITION CONTAINING THEREOF, METHOD OF SYNTHESIS OF REQUIRED POLYPEPTIDES, NUCLEOTIDE SEQUENCE, EXPRESSION BACTERIAL VECTOR, BACTERIAL HOST CELLS AND COMBINED PROTEIN

摘要

PTH compounds having PTH-like activity and comprising at least one modification, said modification being either 1. at least one radical selected from a L- or D-alpha-amino acid, C2-6alcoxycarbonyl and optionally substituted C1-8alkyl, C2-8alkenyl, C2-8alkynyl, aralkyl, aralkenyl or C3-6cycloalkyl-C1-4alkyl and attached to the terminal amino group of the PTH compound, and/or at least one radical selected from C2-6alcoxycarbonyl and optionally substituted C1-8alkyl, C2-8alkenyl, C2-8alkynyl, aralkyl, aralkenyl or C3-6cycloalkyl-C1-4alkyl and attached to one or more side chain amino groups of the PTH compound, or 2. at least one alpha-amino acid unit in the positions 1 to 38 of a naturally occurring PTH sequence being replaced by a natural or unnatural amino acid unit optionally in protected form, whereby the alpha-amino acid units present in positions 1 and 2 at the amino terminus of the PTH sequence may be replaced by a pseudo-peptide, or a combination of such modifications, in free form or in salt form, have pharmacological activity, e.g. for preventing or treating all bone conditions which are associated with increased calcium depletion or resorption or in which calcium fixation in the bone is desirable.