Lipid membrane permeability of modified c[D-Pen2, D-Pen5]enkephalin peptides

Varadarajan Ramaswami, Xiaoyun Zhu, Marek Romanowski, Ron C. Haaseth, Aleksandra Misicka, Andrzej W. Lipkowski, Victor J Hruby, David F. O'Brien

Research output: Contribution to journalArticle

14 Citations (Scopus)

Abstract

Permeability coefficients of a series of analogues of a potent opioid peptide, c[D-Pen2, D-Pen5]enkephalin, were measured in a model membrane system. The analogues included hydrophobic amino acid substitutions on position 3. Liposomes of a mixed composition consisting of zwitterionic lipids and cholesterol served as the model membranes. The obtained permeability coefficients range between 0.38 x 10-12 and 2.9 x 10-12 cm/s. These data were correlated with the hydrophobicity scale of Nozaki and Tanford (J. Biol. Chem. 246, 1971, 2211-2217) (correlation coefficient = 0.9933) and with determinations of lipid order perturbation by differential scanning calorimetry (correlation coefficient = -0.9779). The reasonably good correlation obtained within the family of analogues substituted on position 3 (Gly, Ala, Leu, Phe) indicates that changes in permeabilities are primarily related to increases in the partition coefficient of the peptide. However, Phe residue added on the N-terminal end of the peptide (position 0) does not appear to follow the observed trend, showing stronger lipid perturbation and lower permeability compared to the Phe3 analog. This observation demonstrates that each class of peptide modifications requires a new basis of permeability analysis and predictions.

Original languageEnglish (US)
Pages (from-to)87-94
Number of pages8
JournalInternational Journal of Peptide and Protein Research
Volume48
Issue number1
StatePublished - 1996

Fingerprint

D-Penicillamine (2,5)-Enkephalin
Membrane Lipids
Permeability
Hydraulic conductivity
Lipids
Peptides
Membranes
Opioid Peptides
Hydrophobicity
Liposomes
Differential scanning calorimetry
Substitution reactions
Cholesterol
Differential Scanning Calorimetry
Amino Acids
Amino Acid Substitution
Hydrophobic and Hydrophilic Interactions
Chemical analysis

Keywords

  • Blood-brain barrier
  • Differential scanning calorimetry
  • Drug delivery
  • Enkephalins
  • Lipid bilayers
  • Liposomes

ASJC Scopus subject areas

  • Biochemistry

Cite this

Ramaswami, V., Zhu, X., Romanowski, M., Haaseth, R. C., Misicka, A., Lipkowski, A. W., ... O'Brien, D. F. (1996). Lipid membrane permeability of modified c[D-Pen2, D-Pen5]enkephalin peptides. International Journal of Peptide and Protein Research, 48(1), 87-94.

Lipid membrane permeability of modified c[D-Pen2, D-Pen5]enkephalin peptides. / Ramaswami, Varadarajan; Zhu, Xiaoyun; Romanowski, Marek; Haaseth, Ron C.; Misicka, Aleksandra; Lipkowski, Andrzej W.; Hruby, Victor J; O'Brien, David F.

In: International Journal of Peptide and Protein Research, Vol. 48, No. 1, 1996, p. 87-94.

Research output: Contribution to journalArticle

Ramaswami, V, Zhu, X, Romanowski, M, Haaseth, RC, Misicka, A, Lipkowski, AW, Hruby, VJ & O'Brien, DF 1996, 'Lipid membrane permeability of modified c[D-Pen2, D-Pen5]enkephalin peptides', International Journal of Peptide and Protein Research, vol. 48, no. 1, pp. 87-94.
Ramaswami, Varadarajan ; Zhu, Xiaoyun ; Romanowski, Marek ; Haaseth, Ron C. ; Misicka, Aleksandra ; Lipkowski, Andrzej W. ; Hruby, Victor J ; O'Brien, David F. / Lipid membrane permeability of modified c[D-Pen2, D-Pen5]enkephalin peptides. In: International Journal of Peptide and Protein Research. 1996 ; Vol. 48, No. 1. pp. 87-94.
@article{975f498047af4c028a70db0779bc41cf,
title = "Lipid membrane permeability of modified c[D-Pen2, D-Pen5]enkephalin peptides",
abstract = "Permeability coefficients of a series of analogues of a potent opioid peptide, c[D-Pen2, D-Pen5]enkephalin, were measured in a model membrane system. The analogues included hydrophobic amino acid substitutions on position 3. Liposomes of a mixed composition consisting of zwitterionic lipids and cholesterol served as the model membranes. The obtained permeability coefficients range between 0.38 x 10-12 and 2.9 x 10-12 cm/s. These data were correlated with the hydrophobicity scale of Nozaki and Tanford (J. Biol. Chem. 246, 1971, 2211-2217) (correlation coefficient = 0.9933) and with determinations of lipid order perturbation by differential scanning calorimetry (correlation coefficient = -0.9779). The reasonably good correlation obtained within the family of analogues substituted on position 3 (Gly, Ala, Leu, Phe) indicates that changes in permeabilities are primarily related to increases in the partition coefficient of the peptide. However, Phe residue added on the N-terminal end of the peptide (position 0) does not appear to follow the observed trend, showing stronger lipid perturbation and lower permeability compared to the Phe3 analog. This observation demonstrates that each class of peptide modifications requires a new basis of permeability analysis and predictions.",
keywords = "Blood-brain barrier, Differential scanning calorimetry, Drug delivery, Enkephalins, Lipid bilayers, Liposomes",
author = "Varadarajan Ramaswami and Xiaoyun Zhu and Marek Romanowski and Haaseth, {Ron C.} and Aleksandra Misicka and Lipkowski, {Andrzej W.} and Hruby, {Victor J} and O'Brien, {David F.}",
year = "1996",
language = "English (US)",
volume = "48",
pages = "87--94",
journal = "International Journal of Peptide and Protein Research",
issn = "0367-8377",
publisher = "Wiley-Blackwell",
number = "1",

}

TY - JOUR

T1 - Lipid membrane permeability of modified c[D-Pen2, D-Pen5]enkephalin peptides

AU - Ramaswami, Varadarajan

AU - Zhu, Xiaoyun

AU - Romanowski, Marek

AU - Haaseth, Ron C.

AU - Misicka, Aleksandra

AU - Lipkowski, Andrzej W.

AU - Hruby, Victor J

AU - O'Brien, David F.

PY - 1996

Y1 - 1996

N2 - Permeability coefficients of a series of analogues of a potent opioid peptide, c[D-Pen2, D-Pen5]enkephalin, were measured in a model membrane system. The analogues included hydrophobic amino acid substitutions on position 3. Liposomes of a mixed composition consisting of zwitterionic lipids and cholesterol served as the model membranes. The obtained permeability coefficients range between 0.38 x 10-12 and 2.9 x 10-12 cm/s. These data were correlated with the hydrophobicity scale of Nozaki and Tanford (J. Biol. Chem. 246, 1971, 2211-2217) (correlation coefficient = 0.9933) and with determinations of lipid order perturbation by differential scanning calorimetry (correlation coefficient = -0.9779). The reasonably good correlation obtained within the family of analogues substituted on position 3 (Gly, Ala, Leu, Phe) indicates that changes in permeabilities are primarily related to increases in the partition coefficient of the peptide. However, Phe residue added on the N-terminal end of the peptide (position 0) does not appear to follow the observed trend, showing stronger lipid perturbation and lower permeability compared to the Phe3 analog. This observation demonstrates that each class of peptide modifications requires a new basis of permeability analysis and predictions.

AB - Permeability coefficients of a series of analogues of a potent opioid peptide, c[D-Pen2, D-Pen5]enkephalin, were measured in a model membrane system. The analogues included hydrophobic amino acid substitutions on position 3. Liposomes of a mixed composition consisting of zwitterionic lipids and cholesterol served as the model membranes. The obtained permeability coefficients range between 0.38 x 10-12 and 2.9 x 10-12 cm/s. These data were correlated with the hydrophobicity scale of Nozaki and Tanford (J. Biol. Chem. 246, 1971, 2211-2217) (correlation coefficient = 0.9933) and with determinations of lipid order perturbation by differential scanning calorimetry (correlation coefficient = -0.9779). The reasonably good correlation obtained within the family of analogues substituted on position 3 (Gly, Ala, Leu, Phe) indicates that changes in permeabilities are primarily related to increases in the partition coefficient of the peptide. However, Phe residue added on the N-terminal end of the peptide (position 0) does not appear to follow the observed trend, showing stronger lipid perturbation and lower permeability compared to the Phe3 analog. This observation demonstrates that each class of peptide modifications requires a new basis of permeability analysis and predictions.

KW - Blood-brain barrier

KW - Differential scanning calorimetry

KW - Drug delivery

KW - Enkephalins

KW - Lipid bilayers

KW - Liposomes

UR - http://www.scopus.com/inward/record.url?scp=0029745378&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=0029745378&partnerID=8YFLogxK

M3 - Article

VL - 48

SP - 87

EP - 94

JO - International Journal of Peptide and Protein Research

JF - International Journal of Peptide and Protein Research

SN - 0367-8377

IS - 1

ER -