Structure−Activity Studies of Conantokins as Human N-Methyl-d-aspartate Receptor Modulators

• Published in: Journal of medicinal chemistry Vol. 42; no. 3; pp. 415 - 426
• Main Authors: Nielsen, Katherine J, Skjærbæk, Niels, Dooley, Michael, Adams, Denise A, Mortensen, Martin, Dodd, Peter R, Craik, David J, Alewood, Paul F, Lewis, Richard J
• Format: Journal Article
• Language: English
• Published: WASHINGTON American Chemical Society 11.02.1999; Amer Chemical Soc
• Subjects: Amino Acid Sequence; Amino Acid Substitution; Biological and medical sciences; Chemistry, Medicinal; Circular Dichroism; Conotoxins; Dizocilpine Maleate - metabolism; Excitatory Amino Acid Antagonists - chemistry; Excitatory Amino Acid Antagonists - pharmacology; Humans; Life Sciences & Biomedicine; Magnetic Resonance Spectroscopy; Medical sciences; Molecular Sequence Data; Mollusk Venoms - chemistry; Mollusk Venoms - pharmacology; Neuropharmacology; Neurotransmitters. Neurotransmission. Receptors; Peptidergic system (neuropeptide, opioid peptide, opiates...). Adenosinergic and purinergic systems; Peptides - chemistry; Peptides - pharmacology; Peptides, Cyclic - chemistry; Peptides, Cyclic - pharmacology; Pharmacology & Pharmacy; Pharmacology. Drug treatments; Protein Structure, Secondary; Receptors, N-Methyl-D-Aspartate - antagonists & inhibitors; Receptors, N-Methyl-D-Aspartate - metabolism; Science & Technology; Structure-Activity Relationship; NMDA RECEPTOR; PEPTIDES; PROTEIN; ANTAGONIST; GAMMA-CARBOXYGLUTAMATE; CHEMICAL-SHIFTS; NMR-SPECTROSCOPY; K+ CHANNEL; COUPLING-CONSTANTS; CONFORMATIONS; Human; Peptides; Central nervous system; In vitro; Structure activity relation; Polypeptide; Affinity; Peptide synthesis; Antagonist; Solid phase; NMDA receptor; Chemical synthesis; Brain (vertebrata)

The activities of conantokin-G (con-G), conantokin-T (con-T), and several novel analogues have been studied using polyamine enhancement of [3H]MK-801 binding to human glutamate−N-methyl-d-aspartate (NMDA) receptors, and their structures have been examined using CD and 1H NMR spectroscopy. The potenc...