Provided is a novel method whereby an amide compound can be produced by highly stereoselectively and efficiently performing amidation between a plurality of amino acids and/or peptides. A compound of general formula (3) is synthesized by forming an amide bond between the carboxyl group on the right side of general formula (1) in a compound represented thereby and the amino group on the left side of general formula (2) in a compound represented thereby, in the presence of a Lewis acid catalyst and a silylating agent [in formulae (1), (2) and (3), each symbol has the same meaning as defined in claims]. ##STR00001##

Provided herein are polymeric α-hydroxy aldehyde or α-hydroxy ketone reagents which can be conjugated to amine-containing compounds to form stable conjugates in a single-step reaction. In selected embodiments, the polymeric reagent itself incorporates an internal proton-abstracting (basic) functional group, to promote more efficient reaction. The substituent is appropriately situated, via a linker if necessary, to position the group for proton abstraction, preferably providing a 4- or 5-bond spacing between the abstracting atom and the hydrogen atom on the α-carbon. Also provided are methods of using the reagents and stable, solubilized conjugates of the reagents with biologically active compounds. In preferred embodiments, the polymeric component of the reagent or conjugate is a polyethylene glycol.

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.

A method for producing an amide, including mixing a first composition containing a carboxylic acid or a carboxylic acid active species, and an organic solvent and a second composition containing an amine having at least one carboxyl group and water and causing the carboxylic acid or the carboxylic acid active species to react with the amine to obtain an amide.

Provided herein are polymeric α-hydroxy aldehyde or α-hydroxy ketone reagents which can be conjugated to amine-containing compounds to form stable conjugates in a single-step reaction. In selected embodiments, the polymeric reagent itself incorporates an internal proton-abstracting (basic) functional group, to promote more efficient reaction. The substituent is appropriately situated, via a linker if necessary, to position the group for proton abstraction, preferably providing a 4- or 5-bond spacing between the abstracting atom and the hydrogen atom on the α-carbon. Also provided are methods of using the reagents and stable, solubilized conjugates of the reagents with biologically active compounds. In preferred embodiments, the polymeric component of the reagent or conjugate is a polyethylene glycol.

Disclosed are a ring-modified proline short peptide compound and the use thereof, and specifically disclosed is a compound represented by formula (X) or a pharmaceutically acceptable salt thereof.

##STR00001##

A method for preparing an analysis sample includes providing a sample containing a glycan, and performing an amidation reaction through contacting the sample with an amidation reaction solution having a pH of 7.7 or more, the amidation reaction solution containing at least one first compound which is to be reacted with a lactone included in the glycan, and which is selected from the group consisting of ammonia to be reacted with a lactone included in the glycan, primary amines having one or no carbon atom directly linked to a carbon atom linked to an amino group, hydrazine, hydrazine derivatives, hydroxylamine, and salts thereof, and alkalinizing agents to amidate the lactone, wherein when the alkalinizing agent is an amine, the alkalinizing agent is at least one amine selected from the group consisting of branched primary amines in which two or more carbon atoms are directly linked to a carbon atom linked to an amino group, secondary amines, and tertiary amines.

Provided herein are polymeric α-hydroxy aldehyde or α-hydroxy ketone reagents which can be conjugated to amine-containing compounds to form stable conjugates in a single-step reaction. In selected embodiments, the polymeric reagent itself incorporates an internal proton-abstracting (basic) functional group, to promote more efficient reaction. The substituent is appropriately situated, via a linker if necessary, to position the group for proton abstraction, preferably providing a 4- or 5-bond spacing between the abstracting atom and the hydrogen atom on the α-carbon. Also provided are methods of using the reagents and stable, solubilized conjugates of the reagents with biologically active compounds. In preferred embodiments, the polymeric component of the reagent or conjugate is a polyethylene glycol.

A method for preparing interleukin-2 or an interleukin-2 analogue formed by at least three building blocks includes: synthesizing the at least three building blocks, whereby for each building block the C-terminal residue comprises an α-keto group and/or the N-terminal residue comprises a cyclic hydroxylamine; coupling the at least three building blocks by KAHA ligation resulting in a depsipeptide; and rearranging the depsipeptide to obtain interleukin-2 or an interleukin-2 analogue.

Provided is a novel method whereby an amide compound can be produced by highly stereoselectively and efficiently performing amidation between a plurality of amino acids and/or peptides. A compound of general formula (3) is synthesized by forming an amide bond between the carboxyl group on the right side of general formula (1) in a compound represented thereby and the amino group on the left side of general formula (2) in a compound represented thereby, in the presence of a Lewis acid catalyst and a silylating agent [in formulae (1), (2) and (3), each symbol has the same meaning as defined in claims