meterelin Property

Density 

1.47±0.1 g/cm3(Predicted)

pka

9.82±0.15(Predicted)

Hazard and Precautionary Statements (GHS)

meterelin Chemical Properties,Usage,Production

Originator

Avolerin,Mediolanum

Manufacturing Process

It is well known that the incorporation or substitution of a D-tryptophan residue into a biologically active peptide chain enhances the activity of that chain. Furthermore, such incorporation or substitution will prolong the biological activity. The prolonged and enhanced effectiveness of such peptides probably relates the increased resistance to degradation by peptidases.
[D-2-Methyl-Trp6] LHRH and [Des-Gly10-D-2-methyl-Trp6-Pro-ethylamide9] LHRH. 2-Methyl-tryptophan is known (cf. H.N. Rydon, J. Chem. Soc. 1948, 705) and the homologous alkylated derivatives are conveniently prepared from the corresponding 2-alkyl indoles by well known methods (cf. J.P. Li et al., Synthesis (1), 73, 1988). The resolution of the racemic tryptophan derivatives to give the D-enantiomers can also be achieved by a variety of methods (cf. Amino Acids, Peptides and Proteins, Vol. 16, pages 18-20, The Royal Society of Chemistry, London, 1985). The both solution phase or the solid phase method of peptide synthesis can be used to make 5-oxo-L-prolyl-L-histidyl-Ltryptophyl- L-seryl-L-tyrosyl-2-methyl-D-tryptophyl-L-leucyl-L-arginyl-N-ethyl- L-prolinamide (cf. R. Geiger et al., "The Peptides", Academic Press, New York 1981). If the solid phase method is used, peptide synthesizers such as the Applied Biosystem 430A, Bioresearch Sam 9500 or the Beckman Model 990 are preferably used. According to this methodology, the first amino acid is linked to the benzhydrylamine resin and the remaining protected amino acids are then coupled in a stepwise manner using the standard procedures recommended by the manufacturers of the synthesizers.
For instance, amino acid couplings are performed by using symmetrical anhydrides in the Applied Biosystems Synthesizer and diisopropylcarbodiimide in the Bioresearch or Beckman machines. The amino acid derivatives are protected by the tertiary butoxy-carbonyl groups on the α-amino function during the synthesis. The functional groups present in the amino-acid in the side chain are previously protected. For instance, the functional groups of histidine are protected by benzyloxymethyl (His(Bom)), tosyl (His(Tos)), the functional groups of tryptophan by formyl (Trp(For)), those of serine by benzyl (Ser(Bzl)), those of tyrosine by 2-Br-benzyloxycarbonyl (Tyr(2-Br-Z)), those of arginine by tosyl (Arg(Tos)), those of proline by O-benzyl HCl (Pro(OBzl HCl)). The Boc protective groups on the α-aminic function are removed at each stage by treatment with 60% trifluoroacetic acid ("TFA") in dichloromethane. The crude peptides after HF cleavage are purified on a Sephadex G-50 F column in 50% acetic acid or by preparative reverse phase HPLC using gradients of acetonitrile and water containing 0.1% trifluoroacetic acid.

Therapeutic Function

LHRH agonist