Design and synthesis of ladder-shaped polyethers and evaluation of the interaction with transmembrane proteins

Tohru Oishi, Kohei Torikai, Futoshi Hasegawa

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3 Citations (Scopus)

Abstract

Ladder-shaped polyether (LSP) toxins are thought to bind to transmembrane (TM) proteins. To elucidate the interactions of LSPs with TM proteins, artificial ladder-shaped polyethers (ALPs) possessing simple iterative structure with different number of rings were synthesized based on the convergent method via α-cyano ethers. The interaction of these ALPs with TM proteins was evaluated, and we found that the difference of activities among the ALPs can be accounted for by the concept of "hydrophobic matching" i. e. lengths of the hydrophobic region including the side chains of ALPs are ca. 25 Å, which match the lengths of the hydrophobic region of α-helical TM proteins. The partial structure corresponding to the WXYZA'B'C' ring system of maitotoxin (MTX) was synthesized based on the convergent method via α-cyano ethers, and we found that hemolysis of human red blood cells induced by MTX was blocked by the fragment The hydrophobic portion of MTX is expected to be promising molecular probes for identifying the target proteins of MTX.

Original languageEnglish
Pages (from-to)1250-1260
Number of pages11
JournalYuki Gosei Kagaku Kyokaishi/Journal of Synthetic Organic Chemistry
Volume67
Issue number12
DOIs
Publication statusPublished - Dec 1 2009
Externally publishedYes

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Polyethers
Ladders
Ethers
Proteins
Molecular Probes
Blood
Cells
maitotoxin

All Science Journal Classification (ASJC) codes

  • Organic Chemistry

Cite this

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abstract = "Ladder-shaped polyether (LSP) toxins are thought to bind to transmembrane (TM) proteins. To elucidate the interactions of LSPs with TM proteins, artificial ladder-shaped polyethers (ALPs) possessing simple iterative structure with different number of rings were synthesized based on the convergent method via α-cyano ethers. The interaction of these ALPs with TM proteins was evaluated, and we found that the difference of activities among the ALPs can be accounted for by the concept of {"}hydrophobic matching{"} i. e. lengths of the hydrophobic region including the side chains of ALPs are ca. 25 {\AA}, which match the lengths of the hydrophobic region of α-helical TM proteins. The partial structure corresponding to the WXYZA'B'C' ring system of maitotoxin (MTX) was synthesized based on the convergent method via α-cyano ethers, and we found that hemolysis of human red blood cells induced by MTX was blocked by the fragment The hydrophobic portion of MTX is expected to be promising molecular probes for identifying the target proteins of MTX.",
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AU - Torikai, Kohei

AU - Hasegawa, Futoshi

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N2 - Ladder-shaped polyether (LSP) toxins are thought to bind to transmembrane (TM) proteins. To elucidate the interactions of LSPs with TM proteins, artificial ladder-shaped polyethers (ALPs) possessing simple iterative structure with different number of rings were synthesized based on the convergent method via α-cyano ethers. The interaction of these ALPs with TM proteins was evaluated, and we found that the difference of activities among the ALPs can be accounted for by the concept of "hydrophobic matching" i. e. lengths of the hydrophobic region including the side chains of ALPs are ca. 25 Å, which match the lengths of the hydrophobic region of α-helical TM proteins. The partial structure corresponding to the WXYZA'B'C' ring system of maitotoxin (MTX) was synthesized based on the convergent method via α-cyano ethers, and we found that hemolysis of human red blood cells induced by MTX was blocked by the fragment The hydrophobic portion of MTX is expected to be promising molecular probes for identifying the target proteins of MTX.

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