Chemical synthesis of dendrotoxin-i: revision of the reported structure

H. Nishio, T. Inui, Y. Nishiuchi, C.L.C. De Medeiros, E.G. Rowan, A.L. Harvey, E. Katoh, T. Yamazaki

Research output: Contribution to journalArticle

16 Citations (Scopus)

Abstract

Dendrotoxin I (DTX-I) is a 60-residue peptide from the venom of the black mamba snake Dendroaspis polylepis, which binds to neuronal K+ channels. The structure reported previously for DTX-I was synthesized for the first time by a solution procedure. The synthetic product was confirmed to have the correct primary and disulfide structure determined by peptide mapping, sequence analysis and mass measurements. Comparison of synthetic DTX-I with the natural one by high-performance liquid chromatography and capillary zone electrophoresis, as well as by sequence analysis, revealed that the Asn residue at position 12 in the synthetic peptide was Asp in the natural product. Synthesis of DTX-I with Asp at position 12 gave a peptide identical with the natural product in all aspects. NMR analysis of synthetic [Asn12]- and [Asp12]-DTX-I also supported our findings that the Asn residue at position 12 in the DTX-I molecule should be revised as Asp. [Asn12]- and [Asp12]-DTX-I had very similar binding affinities when tested against radiolabeled dendrotoxin binding to rat brain synaptosomal membranes.
LanguageEnglish
Pages355-364
Number of pages9
JournalJournal of Peptide Research
Volume51
Issue number5
DOIs
Publication statusPublished - May 1998

Fingerprint

Elapidae
Peptides
Biological Products
Peptide Mapping
Snakes
Protein Sequence Analysis
Venoms
Capillary Electrophoresis
High performance liquid chromatography
Viperidae
dendrotoxin I
dendrotoxin
Electrophoresis
Disulfides
Sequence Analysis
Rats
Brain
High Pressure Liquid Chromatography
Nuclear magnetic resonance
Membranes

Keywords

  • chemical synthesis
  • dendrotoxin I
  • NMR analysis
  • potassium channel blocker
  • receptor binding assay
  • revised structure

Cite this

Nishio, H. ; Inui, T. ; Nishiuchi, Y. ; De Medeiros, C.L.C. ; Rowan, E.G. ; Harvey, A.L. ; Katoh, E. ; Yamazaki, T. / Chemical synthesis of dendrotoxin-i : revision of the reported structure. In: Journal of Peptide Research. 1998 ; Vol. 51, No. 5. pp. 355-364.
@article{8f830f06666b47efa39d9702b013b1e0,
title = "Chemical synthesis of dendrotoxin-i: revision of the reported structure",
abstract = "Dendrotoxin I (DTX-I) is a 60-residue peptide from the venom of the black mamba snake Dendroaspis polylepis, which binds to neuronal K+ channels. The structure reported previously for DTX-I was synthesized for the first time by a solution procedure. The synthetic product was confirmed to have the correct primary and disulfide structure determined by peptide mapping, sequence analysis and mass measurements. Comparison of synthetic DTX-I with the natural one by high-performance liquid chromatography and capillary zone electrophoresis, as well as by sequence analysis, revealed that the Asn residue at position 12 in the synthetic peptide was Asp in the natural product. Synthesis of DTX-I with Asp at position 12 gave a peptide identical with the natural product in all aspects. NMR analysis of synthetic [Asn12]- and [Asp12]-DTX-I also supported our findings that the Asn residue at position 12 in the DTX-I molecule should be revised as Asp. [Asn12]- and [Asp12]-DTX-I had very similar binding affinities when tested against radiolabeled dendrotoxin binding to rat brain synaptosomal membranes.",
keywords = "chemical synthesis, dendrotoxin I, NMR analysis, potassium channel blocker, receptor binding assay, revised structure",
author = "H. Nishio and T. Inui and Y. Nishiuchi and {De Medeiros}, C.L.C. and E.G. Rowan and A.L. Harvey and E. Katoh and T. Yamazaki",
note = "Strathprints' policy is to record up to 8 authors per publication, plus any additional authors based at the University of Strathclyde. More authors may be listed on the official publication than appear in the Strathprints' record.",
year = "1998",
month = "5",
doi = "10.1111/j.1399-3011.1998.tb01226.x",
language = "English",
volume = "51",
pages = "355--364",
journal = "Journal of Peptide Research",
issn = "1397-002X",
publisher = "Wiley-Blackwell",
number = "5",

}

Nishio, H, Inui, T, Nishiuchi, Y, De Medeiros, CLC, Rowan, EG, Harvey, AL, Katoh, E & Yamazaki, T 1998, 'Chemical synthesis of dendrotoxin-i: revision of the reported structure' Journal of Peptide Research, vol. 51, no. 5, pp. 355-364. https://doi.org/10.1111/j.1399-3011.1998.tb01226.x

Chemical synthesis of dendrotoxin-i : revision of the reported structure. / Nishio, H.; Inui, T.; Nishiuchi, Y.; De Medeiros, C.L.C.; Rowan, E.G.; Harvey, A.L.; Katoh, E.; Yamazaki, T.

In: Journal of Peptide Research, Vol. 51, No. 5, 05.1998, p. 355-364.

Research output: Contribution to journalArticle

TY - JOUR

T1 - Chemical synthesis of dendrotoxin-i

T2 - Journal of Peptide Research

AU - Nishio, H.

AU - Inui, T.

AU - Nishiuchi, Y.

AU - De Medeiros, C.L.C.

AU - Rowan, E.G.

AU - Harvey, A.L.

AU - Katoh, E.

AU - Yamazaki, T.

N1 - Strathprints' policy is to record up to 8 authors per publication, plus any additional authors based at the University of Strathclyde. More authors may be listed on the official publication than appear in the Strathprints' record.

PY - 1998/5

Y1 - 1998/5

N2 - Dendrotoxin I (DTX-I) is a 60-residue peptide from the venom of the black mamba snake Dendroaspis polylepis, which binds to neuronal K+ channels. The structure reported previously for DTX-I was synthesized for the first time by a solution procedure. The synthetic product was confirmed to have the correct primary and disulfide structure determined by peptide mapping, sequence analysis and mass measurements. Comparison of synthetic DTX-I with the natural one by high-performance liquid chromatography and capillary zone electrophoresis, as well as by sequence analysis, revealed that the Asn residue at position 12 in the synthetic peptide was Asp in the natural product. Synthesis of DTX-I with Asp at position 12 gave a peptide identical with the natural product in all aspects. NMR analysis of synthetic [Asn12]- and [Asp12]-DTX-I also supported our findings that the Asn residue at position 12 in the DTX-I molecule should be revised as Asp. [Asn12]- and [Asp12]-DTX-I had very similar binding affinities when tested against radiolabeled dendrotoxin binding to rat brain synaptosomal membranes.

AB - Dendrotoxin I (DTX-I) is a 60-residue peptide from the venom of the black mamba snake Dendroaspis polylepis, which binds to neuronal K+ channels. The structure reported previously for DTX-I was synthesized for the first time by a solution procedure. The synthetic product was confirmed to have the correct primary and disulfide structure determined by peptide mapping, sequence analysis and mass measurements. Comparison of synthetic DTX-I with the natural one by high-performance liquid chromatography and capillary zone electrophoresis, as well as by sequence analysis, revealed that the Asn residue at position 12 in the synthetic peptide was Asp in the natural product. Synthesis of DTX-I with Asp at position 12 gave a peptide identical with the natural product in all aspects. NMR analysis of synthetic [Asn12]- and [Asp12]-DTX-I also supported our findings that the Asn residue at position 12 in the DTX-I molecule should be revised as Asp. [Asn12]- and [Asp12]-DTX-I had very similar binding affinities when tested against radiolabeled dendrotoxin binding to rat brain synaptosomal membranes.

KW - chemical synthesis

KW - dendrotoxin I

KW - NMR analysis

KW - potassium channel blocker

KW - receptor binding assay

KW - revised structure

U2 - 10.1111/j.1399-3011.1998.tb01226.x

DO - 10.1111/j.1399-3011.1998.tb01226.x

M3 - Article

VL - 51

SP - 355

EP - 364

JO - Journal of Peptide Research

JF - Journal of Peptide Research

SN - 1397-002X

IS - 5

ER -