Structure-function relationships of the NMDA receptor antagonist conantokin peptides.
The three members of the conantokin peptide family identified to date are conantokin(con)-G, -T and -R. Their defining attributes include a high relative content of gamma-carboxyglutamic acid (Gla), N-terminal sequence identity, as well as considerable overall sequence homology, and antagonism of the N-methyl-D-aspartate receptor (NMDAR). As promising templates for the design of neuroprotective agents, a thorough evaluation of structure-function relationships in these peptides will be invaluable in aiding rational drug modeling. To this end, a comprehensive assessment of the contributions of individual residues to conantokin structure and function is required. The current review summarizes recent efforts in this area, and also includes the effects of peptide length, as well as structural-stabilization and -destabilization on the structural and inhibitory profiles of an extensive panel ofconantokin derivatives.
Prorok
M
M
Department of Chemistry and Biochemistry, and the W.M.Keck Center for Transgene Research, University of Notre Dame, Indiana 46556, USA.
Castellino
F J
FJ
D000595:Amino Acid Sequence; D000818:Animals; D020916:Conotoxins / Q000737:chemistry / Q000494:pharmacology*; D018691:Excitatory Amino Acid Antagonists / Q000737:chemistry / Q000494:pharmacology*; D006801:Humans; D036341:Intercellular Signaling Peptides and Proteins; D008969:Molecular Sequence Data; D008978:Mollusk Venoms / Q000737:chemistry / Q000494:pharmacology*; D010455:Peptides / Q000737:chemistry / Q000494:pharmacology*; D016194:Receptors, N-Methyl-D-Aspartate / Q000037:antagonists & inhibitors*; D013329:Structure-Activity Relationship
D020916:Conotoxins; D018691:Excitatory Amino Acid Antagonists; D036341:Intercellular Signaling Peptides and Proteins; D008978:Mollusk Venoms; D010455:Peptides; D016194:Receptors, N-Methyl-D-Aspartate; C403083:conantokin R; C063571:conantokin-T; C055407:conotoxin GV