The present invention is generally related to methods of digesting α-amylase/trypsin inhibitors (ATI), and to the treatment and/or prophylaxis of an α-amylase/trypsin inhibitor (ATI) mediated conditions.

The present invention relates to bacterial glutaminyl cyclases and inhibitors thereof for use in the treatment of periodontitis and related conditions, and provides a bacterial glutaminyl cyclase (bacQC); an antibody which recognizes the bacQC, a method for identifying an inhibitor of the bacQC; a compound according to Formula (I); a pharmaceutical composition comprising a bacQC inhibitor compound; a bacQC inhibitor compound and/or a pharmaceutical composition for use in a method for treatment of the human or animal body, for use in a method for therapy or prophylaxis of a bacterial infection, and for use in a method for therapy and/or prophylaxis of an acute, chronic or recurrent periodontal disease.

The invention relates to chemistry of organic substances, pharmacology and medicine, and concerns treating diseases associated and with aberrant activity of cells of the immune system, more particularly for treating lung, respiratory tract and abdominal diseases, radiation sickness and pain syndrome, and also other diseases by using compounds of formula (A) ##STR00001## wherein R.sub.1 is —C(O)—R.sub.2—(O)— or —R.sub.2—C(O)— group, where R.sub.2 is —(CH.sub.2).sub.n-group optionally substituted with one or two C.sub.1-C.sub.6 alkyls, or phenyl, n is an integer from 0 to 4; wherein compounds are selected from the group consisting of the group of compounds as set out in the description. These compounds, as well as pharmaceutically acceptable salts thereof, are highly effective in inhibiting glutaminyl cyclase, which is involved, in particular, in processes of post-translational modification of chemokines and chemotaxis of monocytes, macrophages and other cells of the immune system. This invention also relates to pharmaceutical compositions comprising a therapeutically effective amount of the compounds of formula (A) as defined above.

The invention relates to chemistry of organic substances, pharmacology and medicine, and concerns treating diseases associated and with aberrant activity of cells of the immune system, more particularly for treating lung, respiratory tract and abdominal diseases, radiation sickness and pain syndrome, and also other diseases by using compounds of formula (A)

##STR00001## wherein R.sub.1 is C(O)R.sub.2(O) or R.sub.2C(O) group, where R.sub.2 is (CH.sub.2).sub.n-group optionally substituted with one or two C.sub.1-C.sub.6 alkyls, or phenyl, n is an integer from 0 to 4; wherein compounds are selected from the group consisting of the group of compounds as set out in the description. These compounds, as well as pharmaceutically acceptable salts thereof, are highly effective in inhibiting glutaminyl cyclase, which is involved, in particular, in processes of post-translational modification of chemokines and chemotaxis of monocytes, macrophages and other cells of the immune system. This invention also relates to pharmaceutical compositions comprising a therapeutically effective amount of the compounds of formula (A) as defined above.

The present invention relates to bacterial glutaminyl cyclases and inhibitors thereof for use in the treatment of periodontitis and related conditions, and provides a bacterial glutaminyl cyclase (bacQC); an antibody which recognizes the bacQC, a method for identifying an inhibitor of the bacQC; a compound according to Formula (I); a pharmaceutical composition comprising a bacQC inhibitor compound; a bacQC inhibitor compound and/or a pharmaceutical composition for use in a method for treatment of the human or animal body, for use in a method for therapy or prophylaxis of a bacterial infection, and for use in a method for therapy and/or prophylaxis of an acute, chronic or recurrent periodontal disease.

The invention relates to chemistry of organic substances, pharmacology and medicine, and concerns treating diseases associated and with aberrant activity of cells of the immune system, more particularly for treating lung, respiratory tract and abdominal diseases, radiation sickness and pain syndrome, and also other diseases by using compounds of formula (A)

##STR00001##

wherein

R.sub.1 is C(O)R.sub.2C(O) or R.sub.2C(O).sub.n group, where R.sub.2 is (CH.sub.2).sub.n group optionally substituted with one or two C.sub.1-C.sub.6 alkyls, or phenyl,

n is an integer from 0 to 4;

wherein compounds are selected from the group consisting of the group of compounds as set out in the description. These compounds, as well as pharmaceutically acceptable salts thereof, are highly effective in inhibiting glutaminyl cyclase, which is involved, in particular, in processes of post-translational modification of chemokines and chemotaxis of monocytes, macrophages and other cells of the immune system. This invention also relates to pharmaceutical compositions comprising a therapeutically effective amount of the compounds of formula (A) as defined above.

Disclosed herein is an expression system and uses thereof. The expression system comprises two vectors that express two fusion proteins and a glutaminyl cyclase (QC) with E45Q mutation, so as to autonomously produce a target protein having a N-terminal pyroglutamate (pGlu) residue in a host cell. The first fusion protein is composed of a maltose binding protein (MBP) and a tobacco etch virus protease (TEVP); and the second fusion protein includes in sequence, a thioredoxin, a S-tag, a linker having a TEVP recognition site therein, a target protein, and a (His)-.sub.6-tag. The second fusion protein is cleaved by the TEVP that is expressed by the first fusion protein, and then catalyzed by QC with E45Q mutation so as to autonomously produce the target protein having a N-terminal pGlu residue in the host cell.

The present invention generally relates to enzymatic peptide or protein ligation. In particular, the present invention provides an improved method of enzymatic peptide or protein ligation, which comprises coupling a peptidyl asparaginyl ligase (PAL)-catalyzed ligation to a glutaminyl cyclase (QC)-catalyzed pyroglutamyl formation to improve yield of ligated product.