The present invention provides an improved process for the preparation of high purity glucagon comprising the use of Xmb-protected amino acids, wherein may Xmb include, e.g., 2,4,6-trimethoxybenzyl, 2,4-dimethoxybenzyl, or 2-hydroxy-4-methoxybenzyl. The process also comprises the use of building blocks such as pseudoprolines to avoid aggregation and obtain the product in high yield and purity.

It was found that a peptide compound that has an N-substituted-α,α-disubstituted amino acid residue at the N-terminus and containing a dipeptide residue in which the N-substituted-α,α-disubstituted amino acid residue and an N-substituted amino acid residue are linked together, can be efficiently produced by linking an N-unsubstituted-α,α-disubstituted amino acid whose amino group is protected with an electron-withdrawing protecting group to an N-substituted amino acid or a peptide compound having an N-substituted amino acid residue at the N-terminus, and then allowing a substituent-introducing agent to act in the presence of a specific base to selectively introduce a substituent to the amino group at the N-terminus.

A process for synthesizing peptides or proteins or peptidomimetics by successive elongation, with units, of the second end (primary or secondary amine function, hydroxyl function or thiol function) of a peptide or protein or peptidomimetic chain, characterized in that: said units are selected from the group made up of: α, β or γ-amino acids, α, β or γ-hydroxy acids and α, β or γ-mercapto acids (natural or unnatural or synthetic), the molecules having at least two functional groups; —the first end of said peptide or protein or peptidomimetic is bonded by a covalent bond to an anchoring molecule that is soluble in organic solvents such as halogenated solvents (methylene chloride, chloroform), ethyl acetate, tetrahydrofuran, 2-methyltetrahydrofuran, isooctane, cyclohexane, hexane(s), methylcyclohexane or methyl tert-butyl ether, or aromatic solvents such as benzene or toluene, or any other suitable solvent.

The invention provides a method for the cleavage of Fmoc group characterized by using a solution comprising 3-(diethylamino)propylamine. In particular, it provides a method for the preparation of peptides in solid phase wherein Fmoc protected amino acids are used and the Fmoc group is cleaved by a solution comprising 3-(diethylamino)propylamine.

Methods are disclosed for producing highly purified recombinant human insulin (RHI) having a purity of 99.0% (w/w) or greater, a Total Impurity (not including the related substance desamido Asn.sup.A21-RHI, as specified by USP) of 0.8% (w/w) or less, and an impurity C of 0.1% (w/w) or less. Also disclosed are API compositions of highly purified RHI having a purity of 99.0% (w/w) or greater, a Total Impurity of 0.8% (w/w) or less, and an impurity C of 0.1% (w/w) or less.

The purpose of the present invention is to provide a protecting group which improves the solubility of a compound having a functional group protected with the protecting group in an organic solvent and which is easily separated and purified after a reaction with avoiding solidification or insolubilization. Provided is a benzyl compound represented by Formula (1) where X.sup.1 represents —CH.sub.2OR.sup.14 (where R.sup.14 represents a hydrogen atom, a halogenocarbonyl group, or an active ester-type protecting group), —CH.sub.2NHR.sup.5 (where R.sup.15 represents a hydrogen atom, a linear or branched alkyl group having 1 to 6 carbon atoms, or an aralkyl group), a halogenomethyl group, a methyl azide group, a formyl group, or an oxime; and at least one of R.sup.1, R.sup.2, R.sup.3, R.sup.4, and R.sup.5 is a group represented by Formula (2), and the remainders each represent a hydrogen atom, a halogen atom, an alkyl group having 1 to 4 carbon atoms, or an alkoxy group having 1 to 4 carbon atoms, where R.sup.6 represents a linear or branched alkylene group having 1 to 16 carbon atoms; X.sup.2 represents O or CONR.sup.16 (where R.sup.16 represents a hydrogen atom or an alkyl group having 1 to 4 carbon atoms); and A represents a group represented by Formula (3), (4), (5), (6), (7), (8), (9), (10), (11), (12), or (13).

It was found that a salt formed of an acid and a base having characteristics set forth below can inactivate a deprotecting agent, thereby suppressing redundant peptide elongation: (i) the base is different in type from a base used as a deprotecting agent, and (ii) a conjugate acid of the base has a pKa smaller than that of a conjugate acid of a base used as a deprotecting agent.

The invention provides a new oligopeptide linker intermediate and a preparation method thereof. The preparation method of the oligopeptide intermediate is easily carried out under mild reaction conditions, and since almost no side reactions occur in the reaction, the method produces a high-purity product with fewer impurities and easy to be purified, achieving unexpected technical effects.

The present invention provides a catalyst containing a Brønsted acid as a novel means capable of producing an amide compound by highly stereoselectively and/or highly efficiently causing an amidation reaction in a variety of substrates having a carboxylic ester group and an amino group.

The invention relates to a method for peptide synthesis, wherein said method comprises the steps of reacting a first amino acid or a first peptide with an α-amine protected second amino acid in a solvent selected from the group consisting of water, alcohol, and a mixture of water and alcohol, and removing the α-amine protecting group with a deprotecting solution. The invention further relates to protective agents, their use and an apparatus for carrying out a method for solid phase synthesis of peptides.