Bioactive peptides and peptide derivatives of parathyroid hormone (PTH) and parathyroid hormone-related peptide (PTHrP)

A biologically active peptide consisting essentially of the formula:

• (a) X01ValSerGluX02GlnLeuX03HisX04X05GlyLysX06(SEQ ID NO:1);
• (b) fragments thereof containing amino acids 1-9, 1-10, 1-11, 1-12, or 1-13;
• (c) pharmaceutically acceptable salts thereof;
• or
• (d) N- or C-derivatives thereof;
• wherein:
• X01 is Ser or Ala;
• X02 is Ile or His;
• X03 is Met, Leu or Nle;
• X04 is Asn or Asp;
• X05 is Leu or Lys;
• and
• X06 is His or Ser,
• provided that said peptide is not PTHrP(1-14).

A pharmaceutical composition comprising

• (a) a biologically active peptide at least 85% identical to a peptide consisting essentially of the formula:
• SerValSerGluIleGlnLeuMetHisAsnLeuGlyLysHis (SEQ ID NO:3);
• (b) fragments thereof containing amino acids 1-9, 1-10, 1-11, 1-12, or 1-13;
• (c) pharmaceutically acceptable salts thereof;
• or
• (d) N- or C-derivatives thereof, and a pharmaceutically acceptable carrier.

A pharmaceutical composition comprising

• (a) a biologically active peptide consisting essentially of the formula:
• SerValSerGluIleGlnLeuMetHisAsnLeuGlyLysHis (SEQ ID NO :3);
• (b) fragments thereof containing amino acids 1-9, 1-10, 1-11, 1-12, or 1-13;
• (c) pharmaceutically acceptable salts thereof;
• or
• (d) N- or C-derivatives thereof;
• and a pharmaceutically acceptable carrier.

A pharmaceutical composition comprising

• (a) a biologically active peptide at least 85% identical to a peptide consisting essentially of the formula:
• AlaValSerGluHisGlnLeuLeuHisAspLysGlyLysSer (SEQ ID NO:4);
• (b) fragments thereof containing amino acids 1-9, 1-10, 1-11, 1-12, or 1-13;
• (c) pharmaceutically acceptable salts thereof;
• or
• (d) N- or C-derivatives thereof;
• and a pharmaceutically acceptable carrier.

A pharmaceutical composition comprising

• (a) a biologically active peptide consisting essentially of the formula:
• AlaValSerGluHisGlnLeuLeuHisAspLysGlyLysSer (SEQ ID NO:4);
• (b) fragments thereof containing amino acids 1-9, 1-10, 1-11, 1-12, or 1-13;
• (c) pharmaceutically acceptable salts thereof;
• or
• (d) N- or C-derivatives thereof;
• and a pharmaceutically acceptable carrier.

A nucleic acid molecule consisting essentially of a polynucleotide encoding a biologically active peptide which has an amino acid sequence selected from the group consisting of:

• (a) X01ValSerGluX02GlnLeuX03HisX04X05GlyLysX06(SEQ ID NO:1);
• or
• (b) fragments thereof containing amino acids 1-9, 1-10, 1-11, 1-12, or 1-13;
• wherein:
• X01 is Ser or Ala;
• X02 is Ile or His;
• X03 is Met, Leu or Nle;
• X04 is Asn or Asp;
• X05 is Leu or Lys;
• and
• X06 is His or Ser,
• provided that said peptide is not PTHrP(1-14).

A recombinant DNA molecule comprising:

• (1) an expression control region, said region in operable linkage with (2) a polynucleotide sequence coding for a biologically active peptide, wherein said peptide is selected from the group consisting of:
• (a) X01ValSerGluX02GlnLeuX03HisX04X05GlyLysX06(SEQ ID NO:1);
• or
• (b) fragments thereof containing amino acids 1-9, 1-10, 1-11, 1-12, or 1-13;
• wherein:
• X01 is Ser or Ala;
• X02 is Ile or His;
• X03 is Met, Leu or Nle;
• X04 is Asn or Asp;
• X05 is Leu or Lys;
• and
• X06 is His or Ser,
• provided that said peptide is not PTHrP(1-14).

A method for treating mammalian conditions characterized by decreases in bone mass, which method comprises administering to a subject in need thereof an effective bone mass-increasing amount of a biologically active peptide, wherein said peptide comprises an amino acid sequence at least 85% identical to a member selected from the group consisting essentially of:

• (a) X01ValSerGluX02GlnLeuX03HisX04X05GlyLysX06(SEQ ID NO:1);
• (b) fragments thereof containing amino acids 1-9, 1-10, 1-11, 1-12, or 1-13;
• (c) pharmaceutically acceptable salts thereof;
• or
• (d) N- or C-derivatives thereof;
• wherein:
• X01 is Ser or Ala;
• X02 is Ile or His;
• X03 is Met, Leu or Nle;
• X04 is Asn or Asp;
• X05 is Leu or Lys;
• and
• X06 is His or Ser,
• provided that said peptide is not PTHrP(1-14);
• and a pharmaceutically acceptable carrier.

A method for treating mammalian conditions characterized by decreases in bone mass, which method comprises administering to a subject in need thereof an effective bone mass-increasing amount of a biologically active peptide consisting essentially of the formula:

• (a) X01ValSerGluX02GlnLeuX03HisX04X05GlyLysX06(SEQ ID NO:1);
• (b) fragments thereof containing amino acids 1-9, 1-10, 1-11, 1-12, or 1-13;
• (c) pharmaceutically acceptable salts thereof;
• or
• (d) N- or C-derivatives thereof
• wherein:
• X01 is Ser or Ala;
• X02 is Ile or His;
• X03 is Met, Leu or Nle;
• X04 is Asn or Asp;
• X05 is Leu or Lys;
• and
• X06 is His or Ser,
• provided that said peptide is not PTHrP(1-14);
• and a pharmaceutically acceptable carrier.

A method for the treatment of a patient having need of a biologically active peptide comprising administering a therapeutically effective amount of a peptide, wherein said peptide comprises an amino acid sequence at least 85% identical to a member selected from thc group consisting essentially of:

• (a) a biologically active peptide consisting essentially of the formula:
• SerValSerGluIleGlnLeuMetHisAsnLeuGlyLysHis (SEQ ID NO:3);
• (b) fragments thereof containing amino acids 1-9, 1-10, 1-11, 1-12, or 1-13;
• (c) N- or C-derivatives thereof;
• or
• (d) pharmaceutically acceptable salts thereof;
• and a pharmaceutically acceptable carrier.

A method for treating mammalian conditions characterized by decreases in bone mass, which method comprises administering to a subject in need thereof an effective bone mass-increasing amount of a biologically active peptide consisting essentially of the formula:

• (a) a biologically active peptide consisting essentially of the formula:
• SerValSerGluIleGlnLeuMetHisAsnLeuGlyLysHis (SEQ ID NO:3);
• (b) fragments thereof containing amino acids 1-9, 1-10, 1-11, 1-12, or 1-13;
• (c) N- or C-derivatives thereof;
• or
• (d) pharmaceutically acceptable salts thereof;
• and a pharmaceutically acceptable carrier.

A method for the treatment of a patient having need of a biologically active peptide comprising administering a therapeutically effective amount of a peptide, wherein said peptide comprises an amino acid sequence at least 85% identical to a member selected from the group consisting essentially of:

• (a) a biologically active peptide consisting essentially of the formula:
• AlaValSerGluHisGlnLeuLeuHisAspLysGlyLysSer (SEQ ID NO:4);
• (b) fragments thereof containing amino acids 1-9, -10, 1-11, 1-12, or 1-13;
• (c) N- or C-derivatives thereof;
• or
• (d) pharmaceutically acceptable salts thereof;
• and a pharmaceutically acceptable carrier.

A method for treating mammalian conditions characterized by decreases in bone mass, which method comprises administering to a subject in need thereof an effective bone mass-increasing amount of a biologically active peptide consisting essentially of the formula:

• (a) AlaValSerGluHisGlnLeuLeuHisAspLysGlyLysSer (SEQ ID NO:4);
• (b) fragments thereof containing amino acids 1-9, 1-10, 1-11, 1-12, or 1-13;
• (c) N- or C-derivatives thereof;
• or
• (d) pharmaceutically acceptable salts thereof;
• and a pharmaceutically acceptable carrier.