Antisecretory factor peptides regulating pathological permeability changes

Abstract

A new recombinant protein called Antisecretory Factor (rAF) and homologues and peptide fragments thereof are described. The protein and the homologues and fragments thereof are useful for normalising pathological fluid transport and/or inflammatory reactions in animals including humans. Antibodies against AF or homologues or fragments thereof are described. Nucleic acids coding for the protein or for homologues or fragments thereof are also described as well as vectors and hosts comprising the nucleic acids. The rAF and homologues and fragments thereof could be used for immunodetection, as feed additive for growing animals and as antidiarrheal and drugs against diseases involving edema, dehydration and/or inflammation.

We claim:  
     
         1 . A synthetic protein comprising SEQ ID NO:2 or a homolog or a fragment thereof, and wherein said homolog or fragment of SEQ ID NO:2 comprises formula X 1 VCX 2 X 3 KX 4 R, 
 (a) wherein said formula corresponds to amino acids 35-42 of SEQ ID NO:2;    (b) X 1  is I or is absent;    (c) X 2  is H, R or K;    (d) X 3  is S, L or anther neutral amino acid; and    (d) X 4  is T or A; and    wherein said synthetic protein or homolog or fragment thereof has antisecretory activity when administered after cholera toxin challenge.    
     
     
         2 . A composition comprising the synthetic protein or homolog or fragment of  claim 1 .  
     
     
         3 . The synthetic protein of  claim 1 , wherein said synthetic protein consists of SEQ ID NO:2.  
     
     
         4 . A composition comprising the synthetic protein of  claim 3 .  
     
     
         5 . A synthetic polypeptide comprising (a) amino acids 35-42, (b) amino acids 35-46, (c) amino acids 36-51, (d) amino acids 36-80, or (e) amino acids 1-80 of SEQ ID NO:2, or (f) a peptide of formula X 1 VCX 2 X 3 KX 4 R wherein the formula corresponds to amino acids 35-42 of SEQ ID NO:2 of any of polypeptides (a) to (e), and wherein 
 (i) X 1  is I or is absent;    (ii) X 2  is H, R or K;    (iii) X 3  is S, L or anther neutral amino acid; and    (iv) X 4  is T or A.    
     
     
         6 . A composition comprising the synthetic polypeptide of  claim 5 .  
     
     
         7 . A synthetic polypeptide consisting of a sequence of amino acids selected from the group consisting of (a) amino acids 35-42, (b) amino acids 35-46, (c) amino acids 36-51, (d) amino acids 36-80, and (e) amino acids 1-80 of SEQ ID NO:2.  
     
     
         8 . A composition for use in vertebrates including humans comprising an effective amount of the synthetic protein or fragment or homolog of  claim 1 , wherein said composition has antisecretory activity.  
     
     
         9 . A synthetic composition for use in vertebrates including humans comprising an effective amount of the synthetic polypeptide of  claim 5 , wherein said composition has antisecretory activity.  
     
     
         10 . A method of using the synthetic protein or homolog or fragment of  claim 1  comprising administering an effective amount of the synthetic protein or homolog or fragment to a vertebrate to induce antisecretory activity.  
     
     
         11 . A method of using the synthetic polypeptide of  claim 5  comprising administering an effective amount of the synthetic polypeptide to a vertebrate to induce antisecretory activity.  
     
     
         12 . A method of inhibiting diarrhea in a vertebrate comprising administering the composition of  claim 2 .  
     
     
         13 . A method of inhibiting diarrhea in a vertebrate comprising administering the composition of  claim 6 .  
     
     
         14 . The method of  claim 12 , wherein said vertebrate is a human.  
     
     
         15 . The method of  claim 13 , wherein said vertebrate is a human.  
     
     
         16 . A feed or food for vertebrates including humans comprising an active agent, wherein the active agent is the synthetic protein or a homolog or a fragment thereof of  claim 1  wherein said feed or food has antisecretory activity.  
     
     
         17 . A feed or food for vertebrates comprising an active agent, wherein said active agent is the synthetic polypeptide of  claim 5  and wherein said feed or food has antisecretory activity.  
     
     
         18 . A feed additive comprising the synthetic protein or homolog or fragment thereof of  claim 1 , wherein said feed additive has antisecretory activity.  
     
     
         19 . A feed additive comprising the synthetic polypeptide of  claim 5 , wherein said feed additive has antisecretory activity.