The invention relates to novel methods for synthesizing amanitin derivatives having an amino group attached to position 6′ of the central tryptophan moiety. The invention furthermore relates to a novel amanitin derivative having an amino group attached to position 6′ of the central tryptophan moiety, novel conjugates of such amanitin derivative, and pharmaceutical compositions comprising such conjugates.

The invention relates to novel methods for synthesizing amanitin derivatives having an amino group attached to position 6′ of the central tryptophan moiety. The invention furthermore relates to a novel amanitin derivative having an amino group attached to position 6′ of the central tryptophan moiety, novel conjugates of such amanitin derivative, and pharmaceutical compositions comprising such conjugates.

The present invention relates to the chemical synthesis of α-amanitin and its derivatives. The present invention also relates to intermediate products of the α-amanitin synthesis.

The present invention has an object of shortening the process time and reducing use of a poor solvent for solidifying a carrier (Tag)-peptide component, by removing impurities without conducting solid-liquid separation (condensation, solid-liquid separation and drying operation) of a Tag-peptide component, in an Fmoc method using a Tag for liquid phase peptide synthesis. Provided is the peptide synthesis method that includes the following steps a-d: step a: a carrier-protected amino acid, carrier-protected peptide, or a carrier-protected amino acid amide, and an N-Fmoc-protected amino acid or an N-Fmoc-protected peptide are condensed in an organic solvent or a mixed solution of organic solvents, to obtain an N-Fmoc-carrier-protected peptide, step b: a water-soluble amine is added to the reaction solution after the condensation reaction, step c: the Fmoc group is deprotected from the protected amino group in the presence of a water-soluble amine, and step d: the reaction solution is neutralized by adding an acid, and further, by adding and washing with an acidic aqueous solution, then, by liquid-liquid separation an aqueous layer is removed to obtain an organic layer.

A method for preparing peptides is disclosed, the method comprising a step of forming a peptide bond wherein the carboxyl group of a first amino acid or first peptide is activated and an amino group of the first activated amino acid or first peptide is protected by a protecting group having a water-solubility enhancing group and the activated carboxyl group of the first amino acid or first peptide is reacted with an amino group of a second amino acid or second peptide wherein said carboxyl group of the first amino acid or first peptide is activated in the absence of the second amino acid or second peptide. Peptides comprising a protecting group having a water-solubility enhancing group being bound to the amino group and an activated or free carboxyl group are also disclosed.

The invention provides a method for producing a peptide which comprises the following steps (1) and (2): (1) a step of condensing a C-protected amino acid or a C-protected peptide to a C-terminal of an N-protected amino acid or an N-protected peptide represented by the formula (I):

##STR00001##

wherein Y represents an amino acid in which a C-terminal is unprotected or a peptide in which a C-terminal is unprotected, R.sup.1, R.sup.2 and R.sup.3 each independently represent an aliphatic hydrocarbon group which may have a substituent(s), a total number of the carbon atoms in the R.sup.1R.sup.2R.sup.3Si group is 10 or more, and the R.sup.1R.sup.2R.sup.3SiOC(O) group is bonded to the N-terminal in Y, and (2) a step of removing the protective group at the C-terminal of the peptide obtained in step (1).

The present disclosure relates to the use of a capping and capture reagent in solid phase peptide synthesis. The present disclosure further relates to a method of solid phase peptide synthesis, wherein a capping and capture reagent according to the present disclosure is used. The present disclosure further relates to a method for purification of a (full-length) synthetic peptide via use of a capping and capture reagent according to the present disclosure. The present disclosure also relates to a kit comprising a capping and capture reagent according to the present disclosure and an amino oxy resin or a hydrazine resin and the use of the kit.

The invention relates to a compound or a salt thereof, a method for preparation thereof, and use thereof, wherein the compound has the structure of Formula (1):

##STR00001## the substituents in Formula (1) are as defined in the specification. The compound of Formula (1) or a salt thereof can be attached to a solid-phase resin, on which solid-phase synthesis may be performed.

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 relates to a method for the synthesis of a polypeptide comprising a pre-determined amino acid sequence. The method according to the invention comprises coupling cycles of coupling an N-terminally protected amino acid building block C-terminally at an unprotected N-terminal amino group of an amino acid chain, wherein at least one coupling cycle comprises a coupling step (a), a capping step (b), and a de-protecting step (c).