The present inventions relates to methods involving incubation of undissolved and/or insoluble GLP-1 peptide in solutions or suspensions comprising one or more organic solvents.

The object of the present invention is to provide a method for manufacturing an amino acid polymer more simply and efficiently compared to conventional methods for manufacturing amino acid polymers.

The present invention provides a method for manufacturing an amino acid polymer with thioacid amino acids. Specifically, the manufacturing method of the present invention comprises (A) a step of preparing first and second thioacid amino acids, (B) a step of subjecting said first and second thioacid amino acids to an oxidation reaction to obtain an amino acid polymer linked by peptide bonds. The manufacturing method of the present invention is characterized in that it partially uses thioacid amino acids that do not possess a protecting group.

The object of the present invention is to provide a method for manufacturing an amino acid polymer more simply and efficiently compared to conventional methods for manufacturing amino acid polymers.

The present invention provides a method for manufacturing an amino acid polymer with thioacid amino acids. Specifically, the manufacturing method of the present invention comprises (A) a step of preparing first and second thioacid amino acids, (B) a step of subjecting said first and second thioacid amino acids to an oxidation reaction to obtain an amino acid polymer linked by peptide bonds. The manufacturing method of the present invention is characterized in that it partially uses thioacid amino acids that do not possess a protecting group.

The present invention has an object of providing a peptide synthesis method using a carrier capable of reversibly repeating the dissolved state and the insolubilized state, wherein the problem of an amino acid active species existing in the reaction system in de-protection reaction can be easily solved. The present invention provides a peptide synthesis method comprising the following steps: a step of condensing an N-Fmoc protected amino acid with a peptide having a C-terminal protected with a carrier which is crystallized according to a change of a composition of a dissolving solvent, in the presence of a condensing agent, to obtain an N-Fmoc-C-carrier protected peptide, a step of adding an alkylamine having 1 to 14 carbon atoms or hydroxyl amine to the reaction system, a step of de-protecting the N-terminal, and a step of changing the composition of the solvent dissolving the C-carrier protected peptide, to crystallize and separate the peptide.

The present disclosure relates to methods of preparing and crystallizing β-turn cyclic peptidomimetic salts of formula I: ##STR00001##
where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.10, X, Y and n are as defined in the specification. The present disclosure provides a more efficient route for preparing a crystalline form of β-turn cyclic peptidomimetic compounds and salts thereof.

The present disclosure relates to methods of preparing and crystallizing β-turn cyclic peptidomimetic salts of formula I: ##STR00001##
where R.sub.1, R.sub.2, R.sub.3, R.sub.4, R.sub.5, R.sub.6, R.sub.7, R.sub.8, R.sub.10, X, Y and n are as defined in the specification. The present disclosure provides a more efficient route for preparing a crystalline form of β-turn cyclic peptidomimetic compounds and salts thereof.

The present invention relates to a method of forming a peptide of Formula (I) (P.sup.1-Xaa.sup.1-Xaa.sup.2-P.sup.2) by ligating a first peptide of Formula (II) (P.sup.1-Xaa.sup.1-X—R, wherein X is O or S) to a second peptide of Formula (III) (Xaa.sup.1-Xaa.sup.2-P.sup.2) by enzymatically cleaving the bond between “Asx” and “X” in the first peptide of Formula (II) and ligating the fragment P.sup.1-Asx of the first peptide to the second peptide of Formula (III), wherein the enzymatic cleavage and ligation reaction is catalyzed by butelase 1 (SEQ ID NO: 1) and the peptide of Formula (I) is a depsipeptide, preferably a thiodepsipeptide. Further encompassed are peptides and dendrimeric peptide assemblies prepared using the presently disclosed method, as well as use of the dendrimeric peptide assemblies as a vaccine, medicament, or diagnostic agent, particularly as an antimicrobial agent.

The present invention relates to a method of forming a peptide of Formula (I) (P.sup.1-Xaa.sup.1-Xaa.sup.2-P.sup.2) by ligating a first peptide of Formula (II) (P.sup.1-Xaa.sup.1-X—R, wherein X is O or S) to a second peptide of Formula (III) (Xaa.sup.1-Xaa.sup.2-P.sup.2) by enzymatically cleaving the bond between “Asx” and “X” in the first peptide of Formula (II) and ligating the fragment P.sup.1-Asx of the first peptide to the second peptide of Formula (III), wherein the enzymatic cleavage and ligation reaction is catalyzed by butelase 1 (SEQ ID NO: 1) and the peptide of Formula (I) is a depsipeptide, preferably a thiodepsipeptide. Further encompassed are peptides and dendrimeric peptide assemblies prepared using the presently disclosed method, as well as use of the dendrimeric peptide assemblies as a vaccine, medicament, or diagnostic agent, particularly as an antimicrobial agent.

The present invention relates to the efficient solid-phase synthesis of liraglutide represented by Formula-I. The present invention relates to an efficient process for the preparation of liraglutide by sequential coupling employing solid phase approach. It involves sequential coupling of protected amino acids to prepare backbone of liraglutide and upon completion of linear sequence, synthesis was extended from lysine side chain by adding γ-glutamic acid and palmitic acid, followed by removal of protective groups, cleavage of the peptide from solid support and purification of crude liraglutide obtained. The present invention also involves the usage of inorganic salts during the coupling, wash with HOBt in DMF solution after Fmoc-deprotection step to suppress the aggregation of peptides and ensure reactions are going for completion, and thus avoid deletion sequences and improve the process yield.

The present invention relates to the efficient solid-phase synthesis of liraglutide represented by Formula-I. The present invention relates to an efficient process for the preparation of liraglutide by sequential coupling employing solid phase approach. It involves sequential coupling of protected amino acids to prepare backbone of liraglutide and upon completion of linear sequence, synthesis was extended from lysine side chain by adding γ-glutamic acid and palmitic acid, followed by removal of protective groups, cleavage of the peptide from solid support and purification of crude liraglutide obtained. The present invention also involves the usage of inorganic salts during the coupling, wash with HOBt in DMF solution after Fmoc-deprotection step to suppress the aggregation of peptides and ensure reactions are going for completion, and thus avoid deletion sequences and improve the process yield.