Arginine magic with new counterions up the sleeve

Masamichi Nishihara, Florent Perret, Toshihide Takeuchi, Shiroh Futaki, Adina N. Lazar, Anthony W. Coleman, Naomi Sakai, Stefan Matile

Research output: Contribution to journalArticle

100 Citations (Scopus)

Abstract

The elusive questions how arginine-rich sequences allow peptides and proteins to penetrate cells or to form voltage-gated ion channels are controversial topics of current scientific concern. The possible contributions of exchangeable counterions to these puzzling processes remain underexplored. The objective of this report is to clarify scope and limitations of certain counteranions to modulate cellular uptake and anion carrier activity of oligo/polyarginines. The key finding is that the efficiency of counteranion activators depends significantly on many parameters such as activator-membrane and activator-carrier interactions. This finding is important because it suggests that counteranions can be used to modulate not only efficiency but also selectivity. Specifically, activator efficiencies are found to increase with increasing aromatic surface of the activator, decreasing size of the transported anion, increasing carrier concentration as well as increasing membrane fluidity. Efficiency sequences depend on membrane composition with coronene > pyrene ≫ fullerene > calix[4]arene carboxylates in fluid and crystalline DPPC contrasting to fullerene > calix[4]arene ≈ coronene > pyrene carboxylates in EYPC with or without cholesterol or ergosterol. In HeLa cells, the efficiency of planar activators (pyrene) exceeds that of spherical activators (fullerenes, calixarenes). Polyarginine complexes with pyrene and coronene activators exhibit exceptional excimer emission. Decreasing excimer emission with increasing ionic strength reveals dominant hydrophobic interactions with the most efficient carboxylate activators. Dominance of ion pairing with the inefficient high-affinity sulfate activators is corroborated by the reversed dependence on ionic strength. These findings on activator-carrier and activator-membrane interactions are discussed as supportive of arene-templated guanidinium-carboxylate pairing and interface-directed translocation as possible origins of the superb performance of higher arene carboxylates as activators.

Original languageEnglish
Pages (from-to)1659-1669
Number of pages11
JournalOrganic and Biomolecular Chemistry
Volume3
Issue number9
DOIs
Publication statusPublished - May 7 2005
Externally publishedYes

Fingerprint

sleeves
Magic
Fullerenes
carboxylates
Arginine
pyrenes
membranes
fullerenes
Membranes
Osmolar Concentration
Anions
excimers
Ionic strength
Calixarenes
Ergosterol
Membrane Fluidity
Guanidine
anions
Hydrophobic and Hydrophilic Interactions
Ion Channels

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Physical and Theoretical Chemistry
  • Organic Chemistry

Cite this

Nishihara, M., Perret, F., Takeuchi, T., Futaki, S., Lazar, A. N., Coleman, A. W., ... Matile, S. (2005). Arginine magic with new counterions up the sleeve. Organic and Biomolecular Chemistry, 3(9), 1659-1669. https://doi.org/10.1039/b501472g

Arginine magic with new counterions up the sleeve. / Nishihara, Masamichi; Perret, Florent; Takeuchi, Toshihide; Futaki, Shiroh; Lazar, Adina N.; Coleman, Anthony W.; Sakai, Naomi; Matile, Stefan.

In: Organic and Biomolecular Chemistry, Vol. 3, No. 9, 07.05.2005, p. 1659-1669.

Research output: Contribution to journalArticle

Nishihara, M, Perret, F, Takeuchi, T, Futaki, S, Lazar, AN, Coleman, AW, Sakai, N & Matile, S 2005, 'Arginine magic with new counterions up the sleeve', Organic and Biomolecular Chemistry, vol. 3, no. 9, pp. 1659-1669. https://doi.org/10.1039/b501472g
Nishihara M, Perret F, Takeuchi T, Futaki S, Lazar AN, Coleman AW et al. Arginine magic with new counterions up the sleeve. Organic and Biomolecular Chemistry. 2005 May 7;3(9):1659-1669. https://doi.org/10.1039/b501472g
Nishihara, Masamichi ; Perret, Florent ; Takeuchi, Toshihide ; Futaki, Shiroh ; Lazar, Adina N. ; Coleman, Anthony W. ; Sakai, Naomi ; Matile, Stefan. / Arginine magic with new counterions up the sleeve. In: Organic and Biomolecular Chemistry. 2005 ; Vol. 3, No. 9. pp. 1659-1669.
@article{3314f5f08e8747a8999749feeea3d0bb,
title = "Arginine magic with new counterions up the sleeve",
abstract = "The elusive questions how arginine-rich sequences allow peptides and proteins to penetrate cells or to form voltage-gated ion channels are controversial topics of current scientific concern. The possible contributions of exchangeable counterions to these puzzling processes remain underexplored. The objective of this report is to clarify scope and limitations of certain counteranions to modulate cellular uptake and anion carrier activity of oligo/polyarginines. The key finding is that the efficiency of counteranion activators depends significantly on many parameters such as activator-membrane and activator-carrier interactions. This finding is important because it suggests that counteranions can be used to modulate not only efficiency but also selectivity. Specifically, activator efficiencies are found to increase with increasing aromatic surface of the activator, decreasing size of the transported anion, increasing carrier concentration as well as increasing membrane fluidity. Efficiency sequences depend on membrane composition with coronene > pyrene ≫ fullerene > calix[4]arene carboxylates in fluid and crystalline DPPC contrasting to fullerene > calix[4]arene ≈ coronene > pyrene carboxylates in EYPC with or without cholesterol or ergosterol. In HeLa cells, the efficiency of planar activators (pyrene) exceeds that of spherical activators (fullerenes, calixarenes). Polyarginine complexes with pyrene and coronene activators exhibit exceptional excimer emission. Decreasing excimer emission with increasing ionic strength reveals dominant hydrophobic interactions with the most efficient carboxylate activators. Dominance of ion pairing with the inefficient high-affinity sulfate activators is corroborated by the reversed dependence on ionic strength. These findings on activator-carrier and activator-membrane interactions are discussed as supportive of arene-templated guanidinium-carboxylate pairing and interface-directed translocation as possible origins of the superb performance of higher arene carboxylates as activators.",
author = "Masamichi Nishihara and Florent Perret and Toshihide Takeuchi and Shiroh Futaki and Lazar, {Adina N.} and Coleman, {Anthony W.} and Naomi Sakai and Stefan Matile",
year = "2005",
month = "5",
day = "7",
doi = "10.1039/b501472g",
language = "English",
volume = "3",
pages = "1659--1669",
journal = "Organic and Biomolecular Chemistry",
issn = "1477-0520",
publisher = "Royal Society of Chemistry",
number = "9",

}

TY - JOUR

T1 - Arginine magic with new counterions up the sleeve

AU - Nishihara, Masamichi

AU - Perret, Florent

AU - Takeuchi, Toshihide

AU - Futaki, Shiroh

AU - Lazar, Adina N.

AU - Coleman, Anthony W.

AU - Sakai, Naomi

AU - Matile, Stefan

PY - 2005/5/7

Y1 - 2005/5/7

N2 - The elusive questions how arginine-rich sequences allow peptides and proteins to penetrate cells or to form voltage-gated ion channels are controversial topics of current scientific concern. The possible contributions of exchangeable counterions to these puzzling processes remain underexplored. The objective of this report is to clarify scope and limitations of certain counteranions to modulate cellular uptake and anion carrier activity of oligo/polyarginines. The key finding is that the efficiency of counteranion activators depends significantly on many parameters such as activator-membrane and activator-carrier interactions. This finding is important because it suggests that counteranions can be used to modulate not only efficiency but also selectivity. Specifically, activator efficiencies are found to increase with increasing aromatic surface of the activator, decreasing size of the transported anion, increasing carrier concentration as well as increasing membrane fluidity. Efficiency sequences depend on membrane composition with coronene > pyrene ≫ fullerene > calix[4]arene carboxylates in fluid and crystalline DPPC contrasting to fullerene > calix[4]arene ≈ coronene > pyrene carboxylates in EYPC with or without cholesterol or ergosterol. In HeLa cells, the efficiency of planar activators (pyrene) exceeds that of spherical activators (fullerenes, calixarenes). Polyarginine complexes with pyrene and coronene activators exhibit exceptional excimer emission. Decreasing excimer emission with increasing ionic strength reveals dominant hydrophobic interactions with the most efficient carboxylate activators. Dominance of ion pairing with the inefficient high-affinity sulfate activators is corroborated by the reversed dependence on ionic strength. These findings on activator-carrier and activator-membrane interactions are discussed as supportive of arene-templated guanidinium-carboxylate pairing and interface-directed translocation as possible origins of the superb performance of higher arene carboxylates as activators.

AB - The elusive questions how arginine-rich sequences allow peptides and proteins to penetrate cells or to form voltage-gated ion channels are controversial topics of current scientific concern. The possible contributions of exchangeable counterions to these puzzling processes remain underexplored. The objective of this report is to clarify scope and limitations of certain counteranions to modulate cellular uptake and anion carrier activity of oligo/polyarginines. The key finding is that the efficiency of counteranion activators depends significantly on many parameters such as activator-membrane and activator-carrier interactions. This finding is important because it suggests that counteranions can be used to modulate not only efficiency but also selectivity. Specifically, activator efficiencies are found to increase with increasing aromatic surface of the activator, decreasing size of the transported anion, increasing carrier concentration as well as increasing membrane fluidity. Efficiency sequences depend on membrane composition with coronene > pyrene ≫ fullerene > calix[4]arene carboxylates in fluid and crystalline DPPC contrasting to fullerene > calix[4]arene ≈ coronene > pyrene carboxylates in EYPC with or without cholesterol or ergosterol. In HeLa cells, the efficiency of planar activators (pyrene) exceeds that of spherical activators (fullerenes, calixarenes). Polyarginine complexes with pyrene and coronene activators exhibit exceptional excimer emission. Decreasing excimer emission with increasing ionic strength reveals dominant hydrophobic interactions with the most efficient carboxylate activators. Dominance of ion pairing with the inefficient high-affinity sulfate activators is corroborated by the reversed dependence on ionic strength. These findings on activator-carrier and activator-membrane interactions are discussed as supportive of arene-templated guanidinium-carboxylate pairing and interface-directed translocation as possible origins of the superb performance of higher arene carboxylates as activators.

UR - http://www.scopus.com/inward/record.url?scp=18844398664&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=18844398664&partnerID=8YFLogxK

U2 - 10.1039/b501472g

DO - 10.1039/b501472g

M3 - Article

C2 - 15858647

AN - SCOPUS:18844398664

VL - 3

SP - 1659

EP - 1669

JO - Organic and Biomolecular Chemistry

JF - Organic and Biomolecular Chemistry

SN - 1477-0520

IS - 9

ER -