Conjugates of galactose-binding lectins and clostridial neurotoxins as analgesics
View Patent ↗A class of novel agents that are able to modify nociceptive afferent function is provided. The agents may inhibit the release of neurotransmitters from discrete populations of neurones and thereby reduce or preferably prevent the transmission of afferent pain signals from peripheral to central pain fibers. They comprise a galactose-binding lectin linked to a derivative of a clostridial neurotoxin. The derivative of the clostridial neurotoxin comprises the L-chain, or a fragment thereof, which includes the active proteolytic enzyme domain of the light (L) chain, linked to a molecule or domain with membrane translocating activity. The agents may be used in or as pharmaceuticals for the treatment of pain, particularly chronic pain.
1. An agent for the treatment of pain, which comprises: a galactose-binding or an N-acetylgalactosamine-binding lectin; a light (L) chain or an L-chain fragment of a clostridial neurotoxin, which L-chain or L-chain fragment contains a proteolytically active enzyme domain of the L-chain; and the translocation domain of a clostridial neurotoxin H-chain; wherein the L-chain or L-chain fragment and the translocation domain of the clostridial neurotoxin H-chain are linked by disulfide bond to form LH N , and wherein the LH N and the lectin are linked together by contacting the LH N and the lectin with one or more chemical coupling agents.
2. The agent according to claim 1 , wherein the lectin is of bacterial origin.
3. The agent according to claim 2 , wherein the lectin is obtained from Pseudomonas aeruginosa.
4. The agent according to claim 1 , wherein the LH N and the lectin are linked by SPDP.