A method for producing an amide includes: subjecting carboxylic acids to dehydration condensation or causing a reaction between a carboxylic acid and a haloformic acid ester; and subsequently causing a reaction with a first base and a reaction with an amine to obtain an amide, wherein the reaction with a first base and/or the reaction with an amine is performed by adding an acid thereto.

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 present disclosure provides a method of solid-phase peptide synthesis from the N terminus to C terminus without detectable epimerization of the C-terminal amino acid. The method includes using derivatized amino acids comprising a diamino-aryl group.

The present invention relates to a novel acylating agent, a method for its preparation, and a method of using it for acylating one or more amino groups of an amino acid, a peptide, or a protein. The novel acylating agent may be a compound which comprises a structural element —HN—(CH2)2-(O—((CH2)2)k-O—(CH2)n-CO—, wherein k is an integer in the range of 1-10, and n is an integer in the range of 1-2, being esterified at its —CO-end to the hydroxy group of 3,5-dichloro-2-hydroxy-benzenesulfonic acid (3,5-DC-2-HBSA). This novel acylating agent has an improved stability. Using this agent the acylation process is improved as regards robustness, as well as improving yield and overall production economy. The novel acylating agent is useful for acylating pharmaceutical peptides and proteins such as GLP-1, insulin, pYY, and amylin. The invention also relates to a number of novel GLP-1 precursor peptides and derivatives in which the two N-terminal amino acids have been deleted.

Aspects of the application provide methods of preparing a multiplexed sample for polypeptide sequencing, and compositions, kits and devices useful for the same.

The present disclosure provides a method of solid-phase peptide synthesis from the N terminus to C terminus without detectable epimerization of the C-terminal amino acid.

The present invention relates to a novel acylating agent, a method for its preparation, and a method of using it for acylating one or more amino groups of an amino acid, a peptide, or a protein. The novel acylating agent may be a compound which comprises a structural element HN(CH2)2-(O((CH2)2)k-O(CH2)n-CO, wherein k is an integer in the range of 1-10, and n is an integer in the range of 1-2, being esterified at its CO-end to the hydroxy group of 3,5-dichloro-2-hydroxy-benzenesulfonic acid (3,5-DC-2-HBSA). This novel acylating agent has an improved stability. Using this agent the acylation process is improved as regards robustness, as well as improving yield and overall production economy. The novel acylating agent is useful for acylating pharmaceutical peptides and proteins such as GLP-1, insulin, pYY, and amylin. The invention also relates to a number of novel GLP-1 precursor peptides and derivatives in which the two N-terminal amino acids have been deleted.

The present invention relates to ionic liquids for use in chemical applications and capable of serving the dual function of solvent and liquid support. The ionic liquid lends itself to a method of synthesizing oligomers selected from the group consisting of oligopeptides, oligosaccharides and oligonucleotides, comprising contacting a first monomer unit with an ionic liquid at reaction conditions to provide an ionic liquid bound monomer unit; and contacting the ionic liquid bound monomer unit with at least one further monomer unit at reaction conditions to provide an ionic liquid bound oligomer comprising from 2 to 30 monomer units. The method lends itself to large scale manufacture of oligopeptides, oligosaccharides and oligonucleotides.

The present invention relates to ionic liquids for use in chemical applications and capable of serving the dual function of solvent and liquid support. The ionic liquid lends itself to a method of synthesizing oligomers selected from the group consisting of oligopeptides, oligosaccharides and oligonucleotides, comprising contacting a first monomer unit with an ionic liquid at reaction conditions to provide an ionic liquid bound monomer unit; and contacting the ionic liquid bound monomer unit with at least one further monomer unit at reaction conditions to provide an ionic liquid bound oligomer comprising from 2 to 30 monomer units. The method lends itself to large scale manufacture of oligopeptides, oligosaccharides and oligonucleotides.

The present disclosure discloses a method for synthesizing an amide and/or a polypeptide using a transient protected amino acid as an ammonia component. In this method, an allenone compound is used as a condensing reagent, and a silylation reagent is used to temporarily protect the carboxyl of an amino acid or peptide fragment with amino and carboxyl groups both unprotected first. Then after forming an amide bond with another molecular carboxylic acid or amino acid or -carbonyl alkenyl ester derivative of the C-terminal carboxyl of the polypeptide, the temporarily protected carboxyl is deprotected on site under an acidic condition to obtain a target carboxylic acid product and to cyclicly build new peptide bonds.