Structure-depolarizing activity relationship for achatin-I, a tetrapeptide with a D-Phe residue, and its derivatives toward the crayfish giant axon.
Achatin-I (Gly-D-Phe-Ala-Asp) is a tetrapeptide isolated from the ganglia of an African giant snail (Achatina fulica Férussac). The compound and its derivatives were synthesized, and their effects on the action potential of the crayfish giant axon elicited by electrical stimulation were examined by an intracellular recording method. The membrane potential after the action potential had fallen was elevated by some compounds at an acidic but not neutral pH level. An analysis of the structure-activity relationship for the activity to elevate the afterpotential at an acidic pH level, suggests that the factors favorable for activity were the beta-turn conformation, a beta- or gamma-carboxyl group in the C-terminal residue, appropriate hydrophobicity and/or bulkiness in the protecting groups for the alpha-amino group at the N-terminus, and the number of negative charges in the entire molecule.
Akamatsu
M
M
Department of Agricultural Chemistry, Kyoto University, Japan.
Yamaguchi
H
H
Nishimura
K
K
Sawada
H
H
Nomoto
K
K
Ueno
T
T
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000595:Amino Acid Sequence; D000818:Animals; D003400:Astacoidea; D001369:Axons / Q000187:drug effects / Q000502:physiology*; D017952:Ganglia, Invertebrate / Q000737:chemistry; D066298:In Vitro Techniques; D008564:Membrane Potentials / Q000187:drug effects / Q000502:physiology; D008969:Molecular Sequence Data; D009479:Neuropeptides / Q000302:isolation & purification / Q000494:pharmacology*; D018377:Neurotransmitter Agents / Q000494:pharmacology*; D009842:Oligopeptides / Q000494:pharmacology*; D012908:Snails; D013329:Structure-Activity Relationship
D009479:Neuropeptides; D018377:Neurotransmitter Agents; D009842:Oligopeptides; C059927:achatin I