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.

Provided are a method for producing a peptide compound including a step of using an aromatic heterocyclic compound represented by Formula (1) represented by Formula (1); a protective group-forming reagent including the compound; and the compound. In Formula (1), a ring A represents an aromatic heterocyclic ring, Y.sup.A's each independently represent —OH, —NHR, —SH, or —X.sup.0, where X.sup.0 represents Cl, Br, or I, R.sup.A and R.sup.C each independently represent an aliphatic hydrocarbon group or an organic group having an aliphatic hydrocarbon group, R.sup.Bs' each independently represent a monovalent aliphatic hydrocarbon group, a (1+c)-valent aromatic group, or a (1+c)-valent heteroaromatic group, where, in a case where both a and c is 0, R.sup.B is a monovalent aliphatic hydrocarbon group, and the number of carbon atoms in at least one aliphatic hydrocarbon group of R.sup.A, R.sup.B, or R.sup.C is 12 or more.

##STR00001##

Provided are a method for producing a peptide compound including a step of using an aromatic heterocyclic compound represented by Formula (1) represented by Formula (1); a protective group-forming reagent including the compound; and the compound. In Formula (1), a ring A represents an aromatic heterocyclic ring, Y.sup.A's each independently represent —OH, —NHR, —SH, or —X.sup.0, where X.sup.0 represents Cl, Br, or I, R.sup.A and R.sup.C each independently represent an aliphatic hydrocarbon group or an organic group having an aliphatic hydrocarbon group, R.sup.Bs' each independently represent a monovalent aliphatic hydrocarbon group, a (1+c)-valent aromatic group, or a (1+c)-valent heteroaromatic group, where, in a case where both a and c is 0, R.sup.B is a monovalent aliphatic hydrocarbon group, and the number of carbon atoms in at least one aliphatic hydrocarbon group of R.sup.A, R.sup.B, or R.sup.C is 12 or more.

##STR00001##

The invention provides a method for producing a peptide which includes a step of reacting a peptide in which a C-terminal carboxy group is activated which is obtained by reacting an N-protected peptide represented by the formula (I):

P-AA.sub.1-OH  (I)

a tertiary amine represented by the formula (II):

##STR00001##

and an acid halide in a flow reactor, with a silylated amino acid or peptide obtained by reacting an amino acid or peptide represented by the formula (III):

H-AA.sub.2-OH  (III)

with a silylating agent, in a flow reactor, wherein, in the formulae (I) to (III), AA.sub.1, AA.sub.2, P, R.sup.1, R.sup.2 and R.sup.3 are as defined herein.

The invention provides a method for producing a peptide which includes a step of reacting a peptide in which a C-terminal carboxy group is activated which is obtained by reacting an N-protected peptide represented by the formula (I):

P-AA.sub.1-OH  (I)

a tertiary amine represented by the formula (II):

##STR00001##

and an acid halide in a flow reactor, with a silylated amino acid or peptide obtained by reacting an amino acid or peptide represented by the formula (III):

H-AA.sub.2-OH  (III)

with a silylating agent, in a flow reactor, wherein, in the formulae (I) to (III), AA.sub.1, AA.sub.2, P, R.sup.1, R.sup.2 and R.sup.3 are as defined herein.

Provided are a method for producing a peptide compound including a step of using a hydrazine derivative represented by Formula (1); a reagent for forming a protective group including the compound; and a hydrazine derivative. In Formula (1), a ring A represents an aromatic hydrocarbon ring or an aromatic heterocyclic ring, R represents a hydrogen atom, an amino protective group, an amino acid residue, or a peptide residue, k represents an integer of 1 to 5, n represents 1 or 2, and R.sup.A's each independently represent an aliphatic hydrocarbon group or an organic group having an aliphatic hydrocarbon group.

##STR00001##

Provided herein are water soluble salts of Formula I, wherein R.sup.1, A, and M are defined herein. Also provided herein are methods of preparing the salts of Formula I and methods of using the same. ##STR00001##

Provided herein are water soluble salts of Formula I, wherein R.sup.1, A, and M are defined herein. Also provided herein are methods of preparing the salts of Formula I and methods of using the same. ##STR00001##

The present invention is to provide a method for producing a peptide containing an N-alkylamino acid, which comprises the following Steps (1) to (3). Step (1): a step of mixing an N-terminal protected amino acid or an N-terminal protected peptide with a carboxylic acid halide or a halogenated alkyl formate; Step (2): a step of mixing an amino acid or a peptide in which the N-terminal and the C-terminal are not protected with a trialkylsilylating agent; and Step (3): a step of mixing the product obtained in Step (1) with the product obtained in Step (2).