Basic Overview

cetririx acetate is a synthetic decapeptide. The main chain of the peptide chain is successively connected by ten amino acid residues, forming a specific linear structural basis. From the structural details, the N-terminal acetyl decoration increases the stability of the polypeptide and reduces the possibility of enzymatic hydrolysis of the N-terminal.

mechanism of action

as a gonadotropin, the role of cetrorelix acetate releasing hormone (GnRH) antagonist. GnRH normally binds to specific receptors on the pituitary cell membrane and stimulates the synthesis of gonadotropin cells in the anterior pituitary, releasing luteinizing hormone (LH) and follicle-stimulating hormone (FSH). In contrast to GnRH, cetrorelix acetate can competitively bind to the GnRH receptor on the pituitary cell membrane. Because its structure is similar to GnRH, but it has key amino acid substitutions that make it unable to bind to the receptor like GnRH. In this way, the signal pathway downstream of the receptor is activated, thereby blocking GnRH signal transduction is normal. Specifically, GnRH is prevented by occupying the receptor. The induced release of LH and FSH regulates the reproductive endocrine system in vivo.

Basic information

chinese name: Cetrorick Acetate

english name: Cetrorelix Acetate

company No.: GT-B018

CAS No.: 130143-01-0/120287-85-6

sequence: Ac-3-(2-napthyl)-D-Ala-4-Chloro-D-Phe-3(3-pyridyl)-D-Ala-Ser-Tyr-D-Cit-Leu-Arg-Pro-D-Ala-NH2

molecular formula: C70H92ClN17O14

molecular weight: 1431.06

synthetic method

method one: the method has high product purity, high production efficiency, no amino resin, and is suitable for industrial applications. The method includes the following steps:

using solid phase synthesis, segment 1-9 of cetrorex sequence was connected from C- terminal to N-terminal to obtain Ac-D2. Nal-D4Cpa-D3Pal-Ser (tBu)-Tyr(tBu)-DCit-Leu-Arg(Pbf)-Pro-CTC resin peptide;

(2) Obtain the peptide segment protecting group and deprotection of the fully protected sertreptide Ac-D2-D2, and obtain the fully protected sertreptide. Nal-D4Cpa-D3Pal-Ser(tBu)-Tyr(tBu)-DCit-Leu-Arg(Pbf)-Pro-OH;

(3) The Cetrorelix-A and the step DAla-NH2.HCl obtained in step (2) are subjected to liquid-phase fractional condensation, and the Cetrorelix is completely protected,

(4) Cetrorelix uses the lysis solution to fully protect Cetrorelix, and uses ice ether to precipitate the lysis solution to obtain crude cetrorelix;

(5) Pure product cetrorelix acetate The crude product can be purified by reversed-phase high performance liquid chromatography.

method two: using Fmoc-linker-amino resin as starting material, 9 amino acids with Fmoc protecting group were sequentially connected from C- terminal to N-terminal, Fmoc protecting group was removed, and Ac was connected. -D-2-Nal-OH obtain N-terminal acetylated peptide resin (I. e. Ac-completely protected decapeptide resin), after cleavage by cleavage reagent, use ice ether to precipitate the cleavage solution to obtain crude cetrorelix acetate, which is separated and purified by high performance liquid chromatography column, and then freeze-dried to prepare cetrorelix trifluoroacetate or cetrorelix acetate. The method adopts the principle of minimum protection, uses the N-terminal acetylated amino acid Ac-D-2-Nal-instead of Fmoc OH-D-2-Nal-OH, in the acetylation reagent, avoids the side effects of acetic anhydride and D-citric acid side chain urea group, thereby improving the purity and income of the product.

Method three:

(1) Using AM resin as the starting resin, the amino acids with Fmoc protection group and side chain protection at the N-terminal were sequentially linked according to the main chain peptide sequence of sertraline, where Fmoc-D-ornithine (Dde)-OH is the sixth amino acid in the peptide sequence;

(2) removal of Fmoc protecting group and acetylation of N-terminal;

(3) The Dde protecting group of the D-ornithine side chain was removed by a mixed solution composed of water and DMF, and tert-butyl isocyanate was added to decorate the D-ornithine side chain of the decapeptide resin, thereby obtaining a completely protected cetrorelix peptide resin;

(4) Cetrorelix acetate is the final product obtained by cleavage, purification, desalting and lyophilization. This method has a low content of impurity [D-citrate (acetyl)-cetrep (less than 0.1%). This method is also suitable for large-scale production of cetrerex acetic acid, and has the advantages of high purity and low cost.