Leiurotoxin I (scyllatoxin), a peptide ligand for Ca2(+)-activated K+ channels. Chemical synthesis, radiolabeling, and receptor characterization

Journal Article · Thu Mar 15 04:00:00 EST 1990 · Journal of Biological Chemistry; (USA)

OSTI ID:6921495

Auguste, P; Hugues, M; Grave, B; Gesquiere, J C; Maes, P; Tartar, A; Romey, G; Schweitz, H; Lazdunski, M ^[1]

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1. Institut de Pharmacologie du Centre National de la Recherche Scientifique, Valbonne (France)

Leiurotoxin I (scyllatoxin) is a 31-amino acid polypeptide from the venom of the scorpion Leiurus quinquestriatus hebraeus which has been previously isolated and sequenced by others. This paper reports (i) the total synthesis of this scorpion neurotoxin as well as some aspects of its structure-function relationships; (ii) the synthesis of the analog (Tyr2)leiurotoxin I (scyllatoxin) that has been monoiodinated at high specific radioactivity (2000 Ci/mmol) and has served for the characterization of the properties of {sup 125}I-(Tyr2)leiurotoxin I binding sites (Kd = 80 pM, molecular mass of 27 and 57 kDa for two polypeptides in the leiurotoxin I binding protein); (iii) the similarity of physiological actions between leiurotoxin I and apamin. Both toxins contract Taenia coli previously relaxed with epinephrine, both toxins block the after-hyperpolarization due to Ca2(+)-activated K+ channel activity in muscle cells in culture; (iv) the probable identity of binding sites for apamin and leiurotoxin I. In spite of a different chemical structure apamin competitively inhibits {sup 125}I-(Tyr2) leiurotoxin I binding and vice versa. Moreover, the peculiar effects of K+ on {sup 125}I-(Tyr2)leiurotoxin I binding are identical to those previously observed for {sup 125}I-apamin binding.

• OSTI ID: 6921495
• Journal Information: Journal of Biological Chemistry; (USA), Journal Name: Journal of Biological Chemistry; (USA) Vol. 265:8; ISSN JBCHA; ISSN 0021-9258
• Country of Publication: United States
• Language: English

Related Subjects

550201* -- Biochemistry-- Tracer Techniques
59 BASIC BIOLOGICAL SCIENCES
ALKALI METAL COMPOUNDS
ALKALINE EARTH METAL COMPOUNDS
AMINO ACID SEQUENCE
ANIMALS
ANTIGENS
ARACHNIDS
ARTHROPODS
BETA DECAY RADIOISOTOPES
BIOASSAY
BIOCHEMICAL REACTION KINETICS
BODY
BRAIN
CALCIUM COMPOUNDS
CELL CONSTITUENTS
CELL MEMBRANES
CENTRAL NERVOUS SYSTEM
CHEMICAL COMPOSITION
CHEMICAL PREPARATION
CONTRACTION
DAYS LIVING RADIOISOTOPES
ELECTRON CAPTURE RADIOISOTOPES
ELECTROPHYSIOLOGY
GUINEA PIGS
INTERMEDIATE MASS NUCLEI
INVERTEBRATES
IODINE 125
IODINE ISOTOPES
ISOTOPE APPLICATIONS
ISOTOPES
KINETICS
MAMMALS
MATERIALS
MEMBRANE PROTEINS
MEMBRANES
MOLECULAR STRUCTURE
MOLECULAR WEIGHT
MUSCLES
NERVOUS SYSTEM
NUCLEI
ODD-EVEN NUCLEI
ORGANIC COMPOUNDS
ORGANS
PEPTIDES
PHYSIOLOGY
POLYPEPTIDES
POTASSIUM COMPOUNDS
PROTEINS
RADIOISOTOPES
RATS
REACTION KINETICS
REAGENTS
RECEPTORS
RODENTS
STRUCTURE-ACTIVITY RELATIONSHIPS
SYNTHESIS
TOXIC MATERIALS
TOXINS
TRACER TECHNIQUES
VENOMS
VERTEBRATES