Transglutaminase linkage of agents to tissue

Abstract

Methods, products and kits are provided for attaching agents to body tissues using transglutaminase.

1 . A method for attaching a non-corneocyte, nonlabeling, agent to a body tissue comprising: 
 applying to the body tissue a conjugate of the agent and a linking molecule having a carboxamide, the linking molecule being a carboxamide-bearing substrate of transglutaminase,    applying to the body tissue transglutaminase in an amount effective for crosslinking the conjugate to the body tissue via the linking group, and    allowing said crosslinking to occur.    
   
   
       2 . The method of  claim 1 , wherein the linking molecule is a molecule selected from the group consisting of: 
 (a) at least one glutamine,    (b) at least two contiguous linked glutamines,    (c) at least three contiguous linked glutamines,    (d) at least four contiguous linked glutamines, and    (e) at least five contiguous linked glutamines.    
   
   
       3 . (canceled)  
   
   
       4 . The method of  claim 1 , wherein the linking molecule comprises a polymer of amino acids and wherein at least 20% of the amino acids are glutamines.  
   
   
       5 - 6 . (canceled)  
   
   
       7 . The method of  claim 1 , further comprising first attaching to the body tissue a complementary linking molecule bearing multiple reactive aliphatic amines, the complementary linking molecule being an aliphatic amine substrate of transglutaminase, wherein the conjugate is crosslinked to the body tissue by crosslinking the aliphatic amines of the complementary linking molecule and the carboxamide of linking molecule to one another by said transglutaminase.  
   
   
       8 . The method of  claim 7 , wherein the complementary linking molecule is attached to the body tissue by 
 applying to the body tissue the complementary linking molecule,    applying to the body tissue an amount of transglutaminase effective for crosslinking the complementary linking molecule to the body tissue, and    allowing said crosslinking to occur.    
   
   
       9 - 19 . (canceled)  
   
   
       20 . A method for attaching an agent to a body tissue comprising 
 first attaching to the body-tissue a linking molecule that is covalently bondable to the agent in the presence of transglutaminase, then    applying to the body tissue having the linking molecule attached thereto an agent that is a substrate of transglutaminase and that is covalently bondable to the linking molecule in the presence of transglutaminase,    applying to the body tissue transglutaminase in an amount effective in crosslinking the agent to the linking molecule, and    allowing said crosslinking to occur.    
   
   
       21 - 45 . (canceled)  
   
   
       46 . A method for attaching a nonextracellular matrix protein, agent to a body tissue comprising: 
 applying to the body tissue a conjugate of the agent and a linking molecule, the linking molecule being a polymer carrying at least 3 aliphatic amines spaced along the polymer,    applying to the body tissue transglutaminase in an amount effective for crosslinking the linking molecule to the body tissue, and    allowing the crosslinking to occur.    
   
   
       47 - 73 . (canceled)