The relationship between micelle formation and biological activity of peptide 562–572 of luteinizing hormone receptor modified with decanoyl radicals

Research output

Abstract

Lipophilic derivatives of peptides corresponding to cytoplasmic regions of G protein-coupled receptors (GPCR) can act as intracellular agonists. Our previous work showed that peptides corresponding to residues 562–572 of luteinizing hormone receptor and modified with palmitate or decanoate at the C-terminus activate adenylate cyclase in rat testes. The stimulating effect of peptide 562–572 modified with decanoates at both the N- and the C-termini (peptide IV) reached its maximum at the peptide concentration of 10–5 M and diminished with further increase in its concentration. It was supposed that this effect was due to peptide IV ability to form micelles. To verify this hypothesis, the relationship between biological activity, hydrophobicity, and ability to form micelles was investigated for peptide IV and other acylated derivatives of peptide 562–572, including those carrying C-terminal decanoate (peptide III) and palmitate (peptide VI) moieties. It was found that the stimulating effect of peptide IV taken in the concentration of 10–5 M on adenylate cyclase activity in plasma membranes of rat testes and ovaries was only slightly lower than that of peptide VI and higher than the effect of peptide III. At the concentration of 10–3 M, the effect of peptide IV was 20–27% lower and amounted to only 50–51 and 87–88% of the effects of peptides VI and III, respectively. In spite of its high hydrophobicity, peptide IV was characterized with an abnormally low retention time when eluted from a Nucleosil C8 column during reverse-phase HPLC: it was even lower than the retention time of nonmodified peptide 562–572. However, the retention time of peptide IV, but not of other peptides, increased significantly when the eluent contained a higher proportion of trifluoroacetic acid, which disrupts micellelike structures (0.5 instead of 0.1%). The surface tension of peptide IV solution in water slightly decreased with increasing peptide concentration, but rapidly dropped and reached a plateau at the concentration of 7 × 10–6 M, which indicates the beginning of micelle formation. Thus, peptide IV in the concentrations above 10–5 M forms micelles, which prevents it from interacting with the receptor. The ability of GPCR peptides to aggregate and form micelles should be taken into account in the development of their new membrane-active analogs.

Original languageEnglish
Pages (from-to)227-233
Number of pages7
JournalCell and Tissue Biology
Volume11
Issue number3
DOIs
Publication statusPublished - 1 May 2017

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LH Receptors
Micelles
Peptides
Decanoates
Palmitates
G-Protein-Coupled Receptors
Hydrophobic and Hydrophilic Interactions
Adenylyl Cyclases
Testis

Scopus subject areas

  • Cell Biology

Cite this

@article{c6b8788a8a074b23bb9466c527ffb6ff,
title = "The relationship between micelle formation and biological activity of peptide 562–572 of luteinizing hormone receptor modified with decanoyl radicals",
abstract = "Lipophilic derivatives of peptides corresponding to cytoplasmic regions of G protein-coupled receptors (GPCR) can act as intracellular agonists. Our previous work showed that peptides corresponding to residues 562–572 of luteinizing hormone receptor and modified with palmitate or decanoate at the C-terminus activate adenylate cyclase in rat testes. The stimulating effect of peptide 562–572 modified with decanoates at both the N- and the C-termini (peptide IV) reached its maximum at the peptide concentration of 10–5 M and diminished with further increase in its concentration. It was supposed that this effect was due to peptide IV ability to form micelles. To verify this hypothesis, the relationship between biological activity, hydrophobicity, and ability to form micelles was investigated for peptide IV and other acylated derivatives of peptide 562–572, including those carrying C-terminal decanoate (peptide III) and palmitate (peptide VI) moieties. It was found that the stimulating effect of peptide IV taken in the concentration of 10–5 M on adenylate cyclase activity in plasma membranes of rat testes and ovaries was only slightly lower than that of peptide VI and higher than the effect of peptide III. At the concentration of 10–3 M, the effect of peptide IV was 20–27{\%} lower and amounted to only 50–51 and 87–88{\%} of the effects of peptides VI and III, respectively. In spite of its high hydrophobicity, peptide IV was characterized with an abnormally low retention time when eluted from a Nucleosil C8 column during reverse-phase HPLC: it was even lower than the retention time of nonmodified peptide 562–572. However, the retention time of peptide IV, but not of other peptides, increased significantly when the eluent contained a higher proportion of trifluoroacetic acid, which disrupts micellelike structures (0.5 instead of 0.1{\%}). The surface tension of peptide IV solution in water slightly decreased with increasing peptide concentration, but rapidly dropped and reached a plateau at the concentration of 7 × 10–6 M, which indicates the beginning of micelle formation. Thus, peptide IV in the concentrations above 10–5 M forms micelles, which prevents it from interacting with the receptor. The ability of GPCR peptides to aggregate and form micelles should be taken into account in the development of their new membrane-active analogs.",
keywords = "adenylate cyclase, decanoyl radical, hydrophobicity, luteinizing hormone receptor, micelle formation, peptide",
author = "Shpakova, {E. A.} and Sorokoumov, {V. N.} and Akent’ev, {A. V.} and Derkach, {K. V.} and Tennikova, {T. B.} and Shpakov, {A. O.}",
year = "2017",
month = "5",
day = "1",
doi = "10.1134/S1990519X17030105",
language = "English",
volume = "11",
pages = "227--233",
journal = "Cell and Tissue Biology",
issn = "1990-519X",
publisher = "МАИК {"}Наука/Интерпериодика{"}",
number = "3",

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TY - JOUR

T1 - The relationship between micelle formation and biological activity of peptide 562–572 of luteinizing hormone receptor modified with decanoyl radicals

AU - Shpakova, E. A.

AU - Sorokoumov, V. N.

AU - Akent’ev, A. V.

AU - Derkach, K. V.

AU - Tennikova, T. B.

AU - Shpakov, A. O.

PY - 2017/5/1

Y1 - 2017/5/1

N2 - Lipophilic derivatives of peptides corresponding to cytoplasmic regions of G protein-coupled receptors (GPCR) can act as intracellular agonists. Our previous work showed that peptides corresponding to residues 562–572 of luteinizing hormone receptor and modified with palmitate or decanoate at the C-terminus activate adenylate cyclase in rat testes. The stimulating effect of peptide 562–572 modified with decanoates at both the N- and the C-termini (peptide IV) reached its maximum at the peptide concentration of 10–5 M and diminished with further increase in its concentration. It was supposed that this effect was due to peptide IV ability to form micelles. To verify this hypothesis, the relationship between biological activity, hydrophobicity, and ability to form micelles was investigated for peptide IV and other acylated derivatives of peptide 562–572, including those carrying C-terminal decanoate (peptide III) and palmitate (peptide VI) moieties. It was found that the stimulating effect of peptide IV taken in the concentration of 10–5 M on adenylate cyclase activity in plasma membranes of rat testes and ovaries was only slightly lower than that of peptide VI and higher than the effect of peptide III. At the concentration of 10–3 M, the effect of peptide IV was 20–27% lower and amounted to only 50–51 and 87–88% of the effects of peptides VI and III, respectively. In spite of its high hydrophobicity, peptide IV was characterized with an abnormally low retention time when eluted from a Nucleosil C8 column during reverse-phase HPLC: it was even lower than the retention time of nonmodified peptide 562–572. However, the retention time of peptide IV, but not of other peptides, increased significantly when the eluent contained a higher proportion of trifluoroacetic acid, which disrupts micellelike structures (0.5 instead of 0.1%). The surface tension of peptide IV solution in water slightly decreased with increasing peptide concentration, but rapidly dropped and reached a plateau at the concentration of 7 × 10–6 M, which indicates the beginning of micelle formation. Thus, peptide IV in the concentrations above 10–5 M forms micelles, which prevents it from interacting with the receptor. The ability of GPCR peptides to aggregate and form micelles should be taken into account in the development of their new membrane-active analogs.

AB - Lipophilic derivatives of peptides corresponding to cytoplasmic regions of G protein-coupled receptors (GPCR) can act as intracellular agonists. Our previous work showed that peptides corresponding to residues 562–572 of luteinizing hormone receptor and modified with palmitate or decanoate at the C-terminus activate adenylate cyclase in rat testes. The stimulating effect of peptide 562–572 modified with decanoates at both the N- and the C-termini (peptide IV) reached its maximum at the peptide concentration of 10–5 M and diminished with further increase in its concentration. It was supposed that this effect was due to peptide IV ability to form micelles. To verify this hypothesis, the relationship between biological activity, hydrophobicity, and ability to form micelles was investigated for peptide IV and other acylated derivatives of peptide 562–572, including those carrying C-terminal decanoate (peptide III) and palmitate (peptide VI) moieties. It was found that the stimulating effect of peptide IV taken in the concentration of 10–5 M on adenylate cyclase activity in plasma membranes of rat testes and ovaries was only slightly lower than that of peptide VI and higher than the effect of peptide III. At the concentration of 10–3 M, the effect of peptide IV was 20–27% lower and amounted to only 50–51 and 87–88% of the effects of peptides VI and III, respectively. In spite of its high hydrophobicity, peptide IV was characterized with an abnormally low retention time when eluted from a Nucleosil C8 column during reverse-phase HPLC: it was even lower than the retention time of nonmodified peptide 562–572. However, the retention time of peptide IV, but not of other peptides, increased significantly when the eluent contained a higher proportion of trifluoroacetic acid, which disrupts micellelike structures (0.5 instead of 0.1%). The surface tension of peptide IV solution in water slightly decreased with increasing peptide concentration, but rapidly dropped and reached a plateau at the concentration of 7 × 10–6 M, which indicates the beginning of micelle formation. Thus, peptide IV in the concentrations above 10–5 M forms micelles, which prevents it from interacting with the receptor. The ability of GPCR peptides to aggregate and form micelles should be taken into account in the development of their new membrane-active analogs.

KW - adenylate cyclase

KW - decanoyl radical

KW - hydrophobicity

KW - luteinizing hormone receptor

KW - micelle formation

KW - peptide

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U2 - 10.1134/S1990519X17030105

DO - 10.1134/S1990519X17030105

M3 - Article

AN - SCOPUS:85020408986

VL - 11

SP - 227

EP - 233

JO - Cell and Tissue Biology

JF - Cell and Tissue Biology

SN - 1990-519X

IS - 3

ER -