Disclosed is a method of synthesizing linaclotide through completely selective formation of three disulfide bonds, comprising the steps of: 1) synthesizing linaclotide precursor resin through solid-phase synthesis; 2) forming the first disulfide bond through solid phase oxidation; 3) forming the second disulfide bond through liquid phase oxidation; and 4) deprotecting methyl in the methyl-protected cysteine, and oxidatively coupling the third disulfide bond to obtain linaclotide. The method has mild reaction conditions with low cost, high yield and high purity product, is a simple and stable process and is suitable for large-scale production.

To develop a protecting group that facilitates separation and purification, after reaction, of a compound including a protected functional group, without solidifying or insolubilizing the compound.

A xanthene compound of by General Formula (1)

##STR00001## (wherein Y is OR.sup.17 (R.sup.17 is a hydrogen atom or an active ester-protecting group), NHR.sup.18 (R.sup.18 is a hydrogen atom, or a linear or branched C.sub.1-C.sub.6 alkyl group or aralkyl group), an azide, a halogen atom, or a carbonyl group formed together with a methylene group; at least one of R.sup.1 to R.sup.8 is represented by Formula (2);

OR.sup.9X-A(2) and a residue is a hydrogen atom, a halogen atom, a C.sub.1-C.sub.4 alkyl group, or a C.sub.1-C.sub.4 alkoxy group, wherein R.sup.9 is a linear or branched C.sub.1-C.sub.16 alkylene group; X is O or CONR.sup.19 (R.sup.19 is a hydrogen atom or a C.sub.1-C.sub.4 alkyl group); and A is represented by Formula (3) or the like

##STR00002## (wherein R.sup.10, R.sup.11, and R.sup.12, the same or different, are a linear or branched C.sub.1-C.sub.6 alkyl group or an aryl group optionally including a substituent; R.sup.13 is a single bond or a linear or branched C.sub.1-C.sub.3 alkylene group; and R.sup.14, R.sup.15, and R.sup.16 are a linear or branched C.sub.1-C.sub.3 alkylene group)).

The present invention provides a method for preparing S-Bz-MAG3 as a precursor of contrast media. Thioglycolic acid and benzoyl chloride are taken for the thiol protection reaction. Next, N,N-dicyclohexylcarbodiimide and N-hydroxysuccinimide are converted to corresponding ester compounds. The corresponding ester compounds then react with triglycine by amide bonding reaction. The product of the reaction is recrystallized using acetone, filtered, and finally flushed using flushing agent to give the final product. This is a bifunctional chelator and can be bridged with 99mTc and 186/188Re effectively and applied to nuclear medicine imaging and tumor radiotherapy. By taking advantage of fewer synthesis steps and ease of operations, complicated separation and purification reactions can be reduced and thus achieving highly productivity of S-Bz-MAG3.

Disclosed is a method of synthesizing linaclotide through completely selective formation of three disulfide bonds, comprising the steps of: 1) synthesizing linaclotide precursor resin through solid-phase synthesis; 2) forming the first disulfide bond through solid phase oxidation; 3) forming the second disulfide bond through liquid phase oxidation; and 4) deprotecting methyl in the methyl-protected cysteine, and oxidatively coupling the third disulfide bond to obtain linaclotide. The method has mild reaction conditions with low cost, high yield and high purity product, is a simple and stable process and is suitable for large-scale production.

A method to make polypeptide antigens with increased resistance to enzymatic degradation and the polypeptide antigens so formed. The method includes fabricating a polypeptide analogue of a native polypeptide antigen in which at least one backbone CO group in the native polypeptide antigen residues is replaced with a backbone CS group.

This invention provides novel methods of stabilizing peptides and peptides so stabilized. In certain embodiments the methods involve providing a peptide containing at least two S bearing residues within the peptide; and reacting the peptide with a di-halogen-aryl-compounds to form a bis(thioether)-aryl-bridge between said two residues.

The present application relates to a method of increasing the production yield of an antibody comprising a functional group using a thiol-reactive additive.