Current Medicinal Chemistry - Volume 11, Issue 23, 2004

Ziconotide (PRIALT®) is a neuroactive peptide in the final stages of clinical development as a novel non-opioid treatment for severe chronic pain. It is the synthetic equivalent of ω-MVIIA, a component of the venom of the marine snail, Conus magus. The mechanism of action underlying ziconotide's therapeutic profile derives from its potent and selective blockade of neuronal N-type voltage-sensitive calcium channels (NV Read More

Expression of the two lymphocyte potassium channels, the voltage-gated channel Kv1.3 and the calcium activated channel IKCa1, changes during differentiation of human T cells. While IKCa1 is the functionally dominant channel in naïve and “early” memory T cells, Kv1.3 is crucial for the activation of terminally differentiated effector memory (TEM) T cells. Because of the involvement of TEM cells in autoimmune processes, Read More

Sodium channels underlie propagated electrical signalling in most excitable cells, including neurons and the myocytes of skeletal muscle and heart. These proteins are targeted by a variety of current therapeutic drugs to combat such maladies as pain, myotonias, epilepsies and cardiac arrhythmias. Typically, these problems are associated with overactivity of sodium channels leading to hyperexcitability in the relevant tis Read More

Dendrotoxins are small proteins isolated from mamba (Dendroaspis) snakes. The original dendrotoxin was found in venom of the Eastern green mamba, Dendroaspis angusticeps, and related proteins were subsequently found in other mamba venoms. The dendrotoxins contain 57-60 amino acid residues crosslinked by three disulphide bridges, and they are homologous to Kunitz-type serine protease inhibitors, such as aprotini Read More

Conantokins are small peptides (17-27 amino acids) found in the venoms of cone snails (Conus sp.) that inhibit the activity of N-methyl-D-aspartate (NMDA) receptors. Unlike most of the peptides characterized from cone snail venom that contain multiple disulfide bridges, conantokins are linear peptides that possess a high degree of alpha-helicity in the presence of divalent cations, and contain gamma-carboxyglutamic acid resid Read More

Botulinum toxin serotype A has proven to be a successful and valuable therapeutic protein when dosage, frequency of treatment and variety of treated clinical conditions are considered. This modern therapeutic protein was predicted by Justinus Kerner, a 19th century German physician, who provided the first detailed clinical description of botulism and its association with faulty sausage production [5-7]. Kerner was preceded b Read More

One of the more challenging issues in medicinal chemistry is the computation of the free energy of ligand binding to macromolecular targets. This allows for the screening of libraries of chemicals for fast and inexpensive identification of lead compounds. Many attempts have been made and several algorithms have been developed for this purpose. Whereas enthalpic contributions are evaluated using methods and equations f Read More

Chemical genomics, which utilizes specially designed small chemical compounds early in the discovery phase of new drugs to explore the life science at various levels, can address biological questions that are not amenable to genetic manipulation or functional genomics / proteomics approaches. Following the development of HT phenotypic assays and DNA expression analysis, the integration of cell-based assays with Read More