Merck + Co., Inc.

Reid J Leonard

Maria L Garcia

Gregory J Kaczorowski

Owen B McManus

Richard J Swanson

Kimberly L Folander

Gloria C Koo

Joanne M Williamson

Chiu-Chuan S Lin

Robert S Slaughter

Scott P Stevens

DNA encoding the .beta. subunit of a mammalian maxi-K potassium channel

Disclosed are nucleic acids encoding the .beta. subunit of the mammalian large-conductance ('maxi-K') potassium channel, cells transformed with such nucleic acids, and .beta. subunit proteins produced by the transformed cells. Within the invention are recombinant host cells expressing .alpha..beta. heteromultimers. Such cells or preparations made from them may be used to screen for pharmacologically active modulators of maxi-K channel activity. Such modulators are potentially useful in treating asthma, pregnant human myometrium, hypertension and angina, cerebral ischemia, and conditions where stimulation of neurotransmitter release is desired, such as in Alzheimer's disease and stimulation of damaged nerves.

Screening array using cells expressing recombinant .alpha. and .beta.

A thirty-nine amino acid peptide, Margatoxin (MgTX), is purified to homogeneity from venom of the scorpion Centruroides margaritatus. The gene encoding MgTX is constructed and this gene is expressed in E. coli, to produce recombinant MgTX. MgTX is a potent and selective inhibitor of a voltage-dependent K.sup.+ channel present in human lymphocytes. MgTX exhibits immunosuppressant activity with human T-lymphocytes, and is useful as an immunosuppressant, in modeling nonpeptidyl K.sup.+ channel blockers, and in establishing biochemical assays based on ligand binding or other protocols with which to screen for other novel modulators of voltage dependent K.sup.+ channels in lymphocytes and other tissues including the brain. As an immunosuppressant, MgTX is useful in the treatment of autoimmune diseases, the prevention of rejection of foreign organ transplants and/or related afflictions, diseases and illnesses.

Scorpion peptide margatoxin with immunosuppressant activity

Growing community of inventors

Westfield, NJ, United States of America

Reid J Leonard