Methods, products, compositions and kits are provided for attaching agents
to tissue with a linking molecule in the presence of transglutaminase. The linking
molecule and/or agent is a substrate of transglutaminase. The agent can be a nonprotein
or an enzyme such as cholinesterase or phosphodiesterase. The transglutaminase
may be exogenously added or be endogenous in tissue. In specific embodiments, the
agent is not a transglutaminase substrate and the linking molecule is a substrate
for transglutaminase containing at least two contiguous linked glutamines or at
least three contiguous linked lysines, and may be a polymer. A conjugate of the
agent and the linking molecule may be applied to tissue, and in the presence of
transglutaminase covalently bonded to the tissue via the linking molecule. A complementary
linking molecule rich in lysines may be first attached to the tissue in the presence
of transglutaminase, and then covalently bonded to a glutamine-containing linking
molecule of the conjugate in the presence of transglutaminase. In another embodiment
a linking molecule containing multiple glutamines is covalently bonded to tissue
in the presence of transglutaminase, and an agent containing multiple lysines is
covalently bonded to the linking molecule in the presence of transglutaminase.
Alternatively, the linking molecule contains multiple lysines and the agent contains
multiple glutamines. Two tissues can be sealed together by holding the tissues
in contact with each other in the presence of transglutalinase.
