Attaching agents to tissue with transglutaminase and a transglutaminase substrate

摘要

Methods, products 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 linking molecule contains at least two contiguous linked glutamines or at least three contiguous linked lysines. 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 transglutaminase.