The invention relates to a method for enzymatically synthesizing an (oligo)peptide, comprising coupling (a) an (oligo)peptide C-terminal ester or thioester and (b) an (oligo)peptide nucleophile having an N-terminally unprotected amine, wherein the coupling is carried out in a fluid comprising water, and wherein the coupling is catalyzed by a subtilisin BPN′ variant or a homologue thereof, which comprises the following mutations compared to subtilisin BPN′ represented by SEQUENCE ID NO: 2 or a homologue sequence thereof: a deletion of the amino acids corresponding to positions 75-83; a mutation at the amino acid position corresponding to S221, the mutation being S221C or S221 selenocysteine; preferably a mutation at the amino acid position corresponding to P225 wherein the amino acid positions are defined according to the sequence of subtilisin BPN′ represented by SEQUENCE ID NO: 2. Further, the invention relates to an enzyme suitable for use as a catalyst in a method of the invention.

A method for producing a polypeptide, includes at least one native ligation step using a peptide functionalized with a selenium group. The selenium peptides and compounds are also described.

The present invention relates to a liquid (or solution)-phase manufacturing process for preparing the decapeptide Degarelix, its protected precursor, and other useful intermediates. The invention further relates to polypeptides useful in the solution-phase manufacturing process and to the purification of Degarelix itself. Degarelix can be obtained by subjecting a Degarelix precursor according to formula II: (P.sub.1)AA.sub.1-AA.sub.2-AA.sub.3-AA.sub.4(P.sub.4)-AA.sub.5-AA.sub.6(P.sub.6)-AA.sub.7-AA.sub.8(P.sub.8)-AA.sub.9-AA.sub.10-NH.sub.2 (II) or a salt or solvate thereof, to a treatment with a cleaving agent in an organic solvent, wherein P.sub.1 is an amino protecting groups; preferably acetyl; P.sub.4 is hydrogen or a hydroxyl protecting group, preferably a hydroxyl protecting group; P.sub.6 is hydrogen or an amino protecting groups; preferably an amino protecting groups; and P.sub.8 is an amino protecting group.

The invention discloses a method for the preparation of a peptide by liquid phase coupling of two fragments, an N-terminal fragment and a C-terminal fragment of the desired peptide, wherein the C-terminal fragment is protected on its C-terminal COOH by a psWang linker; the method is demonstrated with liraglutide wherein the C-terminal fragment carries the Palmitoyl-Glu-OtBu residue on the Lys.

The present invention relates to a process for the preparation of Plecanatide, which comprises preparation of three fragments such as Fragment A (7 amino acids), Fragment B (3 amino acids), Fragment D (6 amino acids) and coupling the fragments to provide Plecanatide followed by purification using buffer system comprising Tris hydrochloride (or) Triethylammonium phosphate.

The objective of the present invention is to provide a method for efficiently producing a long-chain peptide which method is suitable even for an industrial large scale production. The method for producing a long-chain peptide according to the present invention is characterized in comprising a step to deprotect an N-terminal site protected with BOC of a raw material peptide fragment with using a sulfonic acid compound, a step to selectively deprotect a C-terminal site protected with ONBn of a raw material peptide, and a step to condensate the obtained peptide fragment having the deprotected N-terminal site and the obtained peptide fragment having the deprotected C-terminal site in a liquid phase condition.

The present disclosure relates to a novel spherical agglomeration method for proteins, and protein particles made by the spherical agglomeration method. By using continuous oscillatory baffled crystallizer, the method of the present disclosure is capable of maintain the biologically activities and providing protein particles with an average particle size between 1-500 μm.

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 application relates to methods for producing structurally variant polypeptide molecules in parallel using column-free techniques by polypeptide ligation, separation of ligated polypeptides from ligation reactions, folding of polypeptides, and desalting of polypeptides. Further described are methods for determining the effects and properties of structurally variant polypeptide molecules produced in parallel using column-free techniques.

Provided herein is a general method for producing large (more than 400 aa long) D-amino acids proteins, also referred to as mirror image protein (with respect to their naturally occurring L-amino acids counterparts), including RNA/DNA manipulating enzymes, and uses thereof in a wide range of research, practical data storage and medicinal applications.