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Maria A Bednarek - One of the best experts on this subject based on the ideXlab platform.
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cyclic analogs of α melanocyte stimulating hormone αmsh with high Agonist Potency and selectivity at human melanocortin receptor 1b
Peptides, 2008Co-Authors: Maria A Bednarek, Tanya Macneil, Rui Tang, Tung M Fong, Angeles M Cabello, Marta Maroto, Ana TeranAbstract:Abstract α-Melanotropin (αMSH), Ac-Ser 1 -Tyr 2 -Ser 3 -Met 4 -Glu 5 -His 6 -Phe 7 -Arg 8 -Trp 9 -Gly 10 -Lys 11 -Pro 12 -Val 13 -NH 2 , 1 has been long recognized as an important physiological regulator of skin and hair pigmentation in mammals. Binding of this peptide to the melanocortin receptor 1 (MC1R) leads to activation of tyrosinase, the key enzyme of the melanin biosynthesis pathway. In this study, interactions of the human MC1bR (an isoform of the receptor 1a) with the synthetic cyclic analogs of αMSH were studied. These ligands were analogs of MTII, Ac-Nle 4 -cyclo-(Asp 5 -His 6 - d -Phe 7 -Arg 8 -Trp 9 -Lys 10 )-NH 2 , a potent pan-Agonist at the human melanocortin receptors (hMC1,3–5R). In the structure of MTII, the His 6 -D-Phe 7 -Arg 8 -Trp 9 segment has been recognized as “essential” for molecular recognition at the human melanocortin receptors (hMC1,3–5R). Herein, the role of the Trp 9 in the ligand interactions with the hMC1b,3–5R has been reevaluated. Analogs with various amino acids in place of Trp 9 were synthesized and tested in vitro in receptor affinity binding and cAMP functional assays at human melanocortin receptors 1b, 3, 4 and 5 (hMC1b,3–5R). Several of the new peptides were high Potency Agonists (partial) at hMC1bR (EC 50 from 0.5 to 20 nM) and largely inactive at hMC3–5R. The bulky aromatic side chain in position 9, such as that in Trp, was found not to be essential to agonism (partial) of the studied peptides at hMC1bR.
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analogs of α melanocyte stimulating hormone with high Agonist Potency and selectivity at human melanocortin receptor 1b the role of trp9 in molecular recognition
Biopolymers, 2008Co-Authors: Maria A Bednarek, Tanya Macneil, Rui Tang, Tung M Fong, Angeles M Cabello, Marta Maroto, Ana TeranAbstract:α-Melanocyte stimulating hormone (αMSH), Ac-Ser1-Tyr2-Ser3-Met4-Glu5-His6-Phe7-Arg8-Trp9-Gly10-Lys11-Pro12-Val13-NH2, is an endogenous Agonist for the melanocortin receptor 1 (MC1R), the receptor found in the skin, several types of immune cells, and other peripheral sites. Three-dimensional models of complexes of this receptor with αMSH and its synthetic analog NDP-αMSH, Ac-Ser1-Tyr2-Ser3-Nle4-Glu5-His6-D-Phe7-Arg8-Trp9-Gly10-Lys11-Pro12-Val13-NH2, have been previously proposed. In those models, the 6–9 segment of the ligand was considered essential for the ligand-receptor interactions. In this study, we probed the role of Trp9 of NDP-αMSH in interactions with hMC1bR. Analogs of NDP-αMSH with various amino acids in place of Trp9 were synthesized and tested in vitro in receptor affinity binding and cAMP functional assays at human melanocortin receptors 1b, 3, 4, and 5 (hMC1b,3-5R). Several new compounds displayed high Agonist Potency at hMC1bR (EC50 = 0.5–5 nM) and receptor subtype selectivity greater than 2000-fold versus hMC3-5R. The Trp9 residue of NDP-αMSH was determined to be not essential for molecular recognition at hMC1bR. © 2007 Wiley Periodicals, Inc. Biopolymers 89: 401–408, 2008. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
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Analogs of MTII, Lactam Derivatives of α-Melanotropin, Modified at the N-Terminus, and Their Selectivity at Human Melanocortin Receptors 3, 4, and 5
Biochemical and Biophysical Research Communications, 1999Co-Authors: Maria A Bednarek, Tanya Macneil, Rui Tang, Rubana N. Kalyani, Lex H.t. Van Der Ploeg, David H. WeinbergAbstract:Abstract In search for selective Agonists at human melanocortin-4 receptor, proline-substituted analogs of MTII, a potent nonselective Agonist at melanocortin receptors, were prepared by solid-phase syntheses and evaluated for their ability to bind and activate human MC-3, MC-4, and MC-5 receptors. Replacement of Nle 4 with Pro resulted in [Pro 4 ]MTII with affinity to and Agonist Potency at hMC-4R similar to MTII, but with about 400-fold lower Potency at hMC-5R and about 20-fold lower Potency at hMC-3R. The substantial increase in selectivity of [Pro 4 ]MTII with respect to hMC-5R prompted us to investigate additional analogs of MTII with modified N-termini. The Ac-Nle 4 segment, not encompassed in the lactam ring, was substituted with flexible, hydrophobic, or hydrophilic substituents, and also, with residues resembling proline. The similar Agonist Potency of these peptides to that of MTII at hMC-4R but significantly lower activity of these compounds at hMC-5R demonstrated that the N-terminal fragment of MTII has virtually no effect on the binding affinity and activation at hMC-4R, but it is essential for full Potency at hMC-5R.
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structure function studies on the cyclic peptide mt ii lactam derivative of α melanotropin
Peptides, 1999Co-Authors: Maria A Bednarek, Tanya Macneil, Rubana N. Kalyani, Maria V Silva, Byron H Arison, Rueyruey C Huang, David H. WeinbergAbstract:Abstract The alanine-substituted and the retro, enantio, and retro-enantio analogs of MT-II, a potent Agonist at melanocortin (MC) receptors, were prepared by solid-phase synthesis and evaluated for their ability to bind and activate human MC3, MC4, and MC5 receptors. Replacement of His with Ala resulted in [Ala 6 ]-MT-II with affinity and Agonist Potency at human MC3, MC4, and MC5 receptors similar to MT-II. Substitution of Arg with Ala gave compound 100-fold less potent than MT-II, but replacement of Phe or Trp with Ala led to inactive compounds (at the micromolar concentrations). The significant drop of Potency of the retro, enantio, and retro-enantio analogs of MT-II, demonstrated a crucial role of side-chain topology, and to a lesser degree, of peptide backbone in interactions of MT-II with the melanocortin receptors. The nuclear magnetic resonance analysis of MT-II suggested involvement of Phe and Arg residues in H-bonds stabilizing the bent conformations of the peptide backbone.
Ana Teran - One of the best experts on this subject based on the ideXlab platform.
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cyclic analogs of α melanocyte stimulating hormone αmsh with high Agonist Potency and selectivity at human melanocortin receptor 1b
Peptides, 2008Co-Authors: Maria A Bednarek, Tanya Macneil, Rui Tang, Tung M Fong, Angeles M Cabello, Marta Maroto, Ana TeranAbstract:Abstract α-Melanotropin (αMSH), Ac-Ser 1 -Tyr 2 -Ser 3 -Met 4 -Glu 5 -His 6 -Phe 7 -Arg 8 -Trp 9 -Gly 10 -Lys 11 -Pro 12 -Val 13 -NH 2 , 1 has been long recognized as an important physiological regulator of skin and hair pigmentation in mammals. Binding of this peptide to the melanocortin receptor 1 (MC1R) leads to activation of tyrosinase, the key enzyme of the melanin biosynthesis pathway. In this study, interactions of the human MC1bR (an isoform of the receptor 1a) with the synthetic cyclic analogs of αMSH were studied. These ligands were analogs of MTII, Ac-Nle 4 -cyclo-(Asp 5 -His 6 - d -Phe 7 -Arg 8 -Trp 9 -Lys 10 )-NH 2 , a potent pan-Agonist at the human melanocortin receptors (hMC1,3–5R). In the structure of MTII, the His 6 -D-Phe 7 -Arg 8 -Trp 9 segment has been recognized as “essential” for molecular recognition at the human melanocortin receptors (hMC1,3–5R). Herein, the role of the Trp 9 in the ligand interactions with the hMC1b,3–5R has been reevaluated. Analogs with various amino acids in place of Trp 9 were synthesized and tested in vitro in receptor affinity binding and cAMP functional assays at human melanocortin receptors 1b, 3, 4 and 5 (hMC1b,3–5R). Several of the new peptides were high Potency Agonists (partial) at hMC1bR (EC 50 from 0.5 to 20 nM) and largely inactive at hMC3–5R. The bulky aromatic side chain in position 9, such as that in Trp, was found not to be essential to agonism (partial) of the studied peptides at hMC1bR.
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analogs of α melanocyte stimulating hormone with high Agonist Potency and selectivity at human melanocortin receptor 1b the role of trp9 in molecular recognition
Biopolymers, 2008Co-Authors: Maria A Bednarek, Tanya Macneil, Rui Tang, Tung M Fong, Angeles M Cabello, Marta Maroto, Ana TeranAbstract:α-Melanocyte stimulating hormone (αMSH), Ac-Ser1-Tyr2-Ser3-Met4-Glu5-His6-Phe7-Arg8-Trp9-Gly10-Lys11-Pro12-Val13-NH2, is an endogenous Agonist for the melanocortin receptor 1 (MC1R), the receptor found in the skin, several types of immune cells, and other peripheral sites. Three-dimensional models of complexes of this receptor with αMSH and its synthetic analog NDP-αMSH, Ac-Ser1-Tyr2-Ser3-Nle4-Glu5-His6-D-Phe7-Arg8-Trp9-Gly10-Lys11-Pro12-Val13-NH2, have been previously proposed. In those models, the 6–9 segment of the ligand was considered essential for the ligand-receptor interactions. In this study, we probed the role of Trp9 of NDP-αMSH in interactions with hMC1bR. Analogs of NDP-αMSH with various amino acids in place of Trp9 were synthesized and tested in vitro in receptor affinity binding and cAMP functional assays at human melanocortin receptors 1b, 3, 4, and 5 (hMC1b,3-5R). Several new compounds displayed high Agonist Potency at hMC1bR (EC50 = 0.5–5 nM) and receptor subtype selectivity greater than 2000-fold versus hMC3-5R. The Trp9 residue of NDP-αMSH was determined to be not essential for molecular recognition at hMC1bR. © 2007 Wiley Periodicals, Inc. Biopolymers 89: 401–408, 2008. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
Tanya Macneil - One of the best experts on this subject based on the ideXlab platform.
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cyclic analogs of α melanocyte stimulating hormone αmsh with high Agonist Potency and selectivity at human melanocortin receptor 1b
Peptides, 2008Co-Authors: Maria A Bednarek, Tanya Macneil, Rui Tang, Tung M Fong, Angeles M Cabello, Marta Maroto, Ana TeranAbstract:Abstract α-Melanotropin (αMSH), Ac-Ser 1 -Tyr 2 -Ser 3 -Met 4 -Glu 5 -His 6 -Phe 7 -Arg 8 -Trp 9 -Gly 10 -Lys 11 -Pro 12 -Val 13 -NH 2 , 1 has been long recognized as an important physiological regulator of skin and hair pigmentation in mammals. Binding of this peptide to the melanocortin receptor 1 (MC1R) leads to activation of tyrosinase, the key enzyme of the melanin biosynthesis pathway. In this study, interactions of the human MC1bR (an isoform of the receptor 1a) with the synthetic cyclic analogs of αMSH were studied. These ligands were analogs of MTII, Ac-Nle 4 -cyclo-(Asp 5 -His 6 - d -Phe 7 -Arg 8 -Trp 9 -Lys 10 )-NH 2 , a potent pan-Agonist at the human melanocortin receptors (hMC1,3–5R). In the structure of MTII, the His 6 -D-Phe 7 -Arg 8 -Trp 9 segment has been recognized as “essential” for molecular recognition at the human melanocortin receptors (hMC1,3–5R). Herein, the role of the Trp 9 in the ligand interactions with the hMC1b,3–5R has been reevaluated. Analogs with various amino acids in place of Trp 9 were synthesized and tested in vitro in receptor affinity binding and cAMP functional assays at human melanocortin receptors 1b, 3, 4 and 5 (hMC1b,3–5R). Several of the new peptides were high Potency Agonists (partial) at hMC1bR (EC 50 from 0.5 to 20 nM) and largely inactive at hMC3–5R. The bulky aromatic side chain in position 9, such as that in Trp, was found not to be essential to agonism (partial) of the studied peptides at hMC1bR.
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analogs of α melanocyte stimulating hormone with high Agonist Potency and selectivity at human melanocortin receptor 1b the role of trp9 in molecular recognition
Biopolymers, 2008Co-Authors: Maria A Bednarek, Tanya Macneil, Rui Tang, Tung M Fong, Angeles M Cabello, Marta Maroto, Ana TeranAbstract:α-Melanocyte stimulating hormone (αMSH), Ac-Ser1-Tyr2-Ser3-Met4-Glu5-His6-Phe7-Arg8-Trp9-Gly10-Lys11-Pro12-Val13-NH2, is an endogenous Agonist for the melanocortin receptor 1 (MC1R), the receptor found in the skin, several types of immune cells, and other peripheral sites. Three-dimensional models of complexes of this receptor with αMSH and its synthetic analog NDP-αMSH, Ac-Ser1-Tyr2-Ser3-Nle4-Glu5-His6-D-Phe7-Arg8-Trp9-Gly10-Lys11-Pro12-Val13-NH2, have been previously proposed. In those models, the 6–9 segment of the ligand was considered essential for the ligand-receptor interactions. In this study, we probed the role of Trp9 of NDP-αMSH in interactions with hMC1bR. Analogs of NDP-αMSH with various amino acids in place of Trp9 were synthesized and tested in vitro in receptor affinity binding and cAMP functional assays at human melanocortin receptors 1b, 3, 4, and 5 (hMC1b,3-5R). Several new compounds displayed high Agonist Potency at hMC1bR (EC50 = 0.5–5 nM) and receptor subtype selectivity greater than 2000-fold versus hMC3-5R. The Trp9 residue of NDP-αMSH was determined to be not essential for molecular recognition at hMC1bR. © 2007 Wiley Periodicals, Inc. Biopolymers 89: 401–408, 2008. This article was originally published online as an accepted preprint. The “Published Online” date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com
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Analogs of MTII, Lactam Derivatives of α-Melanotropin, Modified at the N-Terminus, and Their Selectivity at Human Melanocortin Receptors 3, 4, and 5
Biochemical and Biophysical Research Communications, 1999Co-Authors: Maria A Bednarek, Tanya Macneil, Rui Tang, Rubana N. Kalyani, Lex H.t. Van Der Ploeg, David H. WeinbergAbstract:Abstract In search for selective Agonists at human melanocortin-4 receptor, proline-substituted analogs of MTII, a potent nonselective Agonist at melanocortin receptors, were prepared by solid-phase syntheses and evaluated for their ability to bind and activate human MC-3, MC-4, and MC-5 receptors. Replacement of Nle 4 with Pro resulted in [Pro 4 ]MTII with affinity to and Agonist Potency at hMC-4R similar to MTII, but with about 400-fold lower Potency at hMC-5R and about 20-fold lower Potency at hMC-3R. The substantial increase in selectivity of [Pro 4 ]MTII with respect to hMC-5R prompted us to investigate additional analogs of MTII with modified N-termini. The Ac-Nle 4 segment, not encompassed in the lactam ring, was substituted with flexible, hydrophobic, or hydrophilic substituents, and also, with residues resembling proline. The similar Agonist Potency of these peptides to that of MTII at hMC-4R but significantly lower activity of these compounds at hMC-5R demonstrated that the N-terminal fragment of MTII has virtually no effect on the binding affinity and activation at hMC-4R, but it is essential for full Potency at hMC-5R.
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structure function studies on the cyclic peptide mt ii lactam derivative of α melanotropin
Peptides, 1999Co-Authors: Maria A Bednarek, Tanya Macneil, Rubana N. Kalyani, Maria V Silva, Byron H Arison, Rueyruey C Huang, David H. WeinbergAbstract:Abstract The alanine-substituted and the retro, enantio, and retro-enantio analogs of MT-II, a potent Agonist at melanocortin (MC) receptors, were prepared by solid-phase synthesis and evaluated for their ability to bind and activate human MC3, MC4, and MC5 receptors. Replacement of His with Ala resulted in [Ala 6 ]-MT-II with affinity and Agonist Potency at human MC3, MC4, and MC5 receptors similar to MT-II. Substitution of Arg with Ala gave compound 100-fold less potent than MT-II, but replacement of Phe or Trp with Ala led to inactive compounds (at the micromolar concentrations). The significant drop of Potency of the retro, enantio, and retro-enantio analogs of MT-II, demonstrated a crucial role of side-chain topology, and to a lesser degree, of peptide backbone in interactions of MT-II with the melanocortin receptors. The nuclear magnetic resonance analysis of MT-II suggested involvement of Phe and Arg residues in H-bonds stabilizing the bent conformations of the peptide backbone.
C G Marr - One of the best experts on this subject based on the ideXlab platform.
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Heterogeneity of thromboxane A2 (TP‐) receptors: evidence from antAgonist but not Agonist Potency measurements
British Journal of Pharmacology, 1991Co-Authors: Paulina M Tymkewycz, R L Jones, N H Wilson, C G MarrAbstract:1 Thromboxane A2 (TP-) receptors in human, rat and rabbit platelets and in smooth muscle of guinea-pig trachea, rat aorta and rabbit aorta have been characterized by measurement of the potencies of Agonists and antAgonists having considerable variations in chemical structure. 2 On each washed platelet system, eight prostanoids induced maximal irreversible aggregation (full Agonists) and the Potency ranking was EP 171 > STA2 > 9,11-azo PGH2 > 9,11-endoxy-10a-homo PGH2 > U-46619 (standard) > PGH2 = 16-p-fluorophenoxy-ω-tetranor PGF2α > 16,16-dimethyl PGF2α. Correlations between the three platelet preparations for both absolute and relative potencies were good. On human platelets, STA2, at concentrations above that required for maximum aggregation, exerted an inhibitory effect which was independent of its interaction with the TP-receptor. 3 Five prostanoids, EP 109, EP 167, EP 204, PTA2 and 16,20-methano PTA2, exhibited partial Agonist activity on the platelet and smooth muscle preparations. There was good agreement between absolute potencies on the six preparations; on platelets Potency was assessed from shape change measurements, since aggregation, when present, always showed a very shallow concentration-response relationship. The magnitude of the maximum response induced by each compound decreased in the order listed above, to the extent that 16,20-methano PTA2 could be treated as a pure antAgonist. 4 With U-46619 as Agonist, the pA2 values of seven antAgonists were found to be very similar on human and rat platelets. The Potency ranking was EP 169 > AH 23848 > EP 092 > ONO 11120 > EP 115 = 16,20-methano PTA2 > BM 13177. There was a similar trend on rabbit platelets but pA2 values were 1.0–1.5 log units smaller; the exception was BM 13177 which had similar affinities. The antagonism produced by EP 169 and AH 23848 was surmountable on rabbit platelets but not on human and rat platelets. 5 None of the antAgonists was highly potent on the rabbit aorta (pA2 values 0.05). 6 The excellent agreement for both full and partial Agonist potencies between the six preparations provides no evidence for TP-receptor subtypes and further suggests that the Agonist recognition sites of the TP-receptors could be very similar, if not identical, in nature. In contrast, the different antAgonist affinities found in this and other published studies indicate heterogeneity of TP-receptors. However, classification into TP1-, TP2-receptors, etc. on the basis of the limited antAgonist data available does not appear appropriate at this time.
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heterogeneity of thromboxane a2 tp receptors evidence from antAgonist but not Agonist Potency measurements
British Journal of Pharmacology, 1991Co-Authors: Paulina M Tymkewycz, R L Jones, N H Wilson, C G MarrAbstract:1 Thromboxane A2 (TP-) receptors in human, rat and rabbit platelets and in smooth muscle of guinea-pig trachea, rat aorta and rabbit aorta have been characterized by measurement of the potencies of Agonists and antAgonists having considerable variations in chemical structure. 2 On each washed platelet system, eight prostanoids induced maximal irreversible aggregation (full Agonists) and the Potency ranking was EP 171 > STA2 > 9,11-azo PGH2 > 9,11-endoxy-10a-homo PGH2 > U-46619 (standard) > PGH2 = 16-p-fluorophenoxy-ω-tetranor PGF2α > 16,16-dimethyl PGF2α. Correlations between the three platelet preparations for both absolute and relative potencies were good. On human platelets, STA2, at concentrations above that required for maximum aggregation, exerted an inhibitory effect which was independent of its interaction with the TP-receptor. 3 Five prostanoids, EP 109, EP 167, EP 204, PTA2 and 16,20-methano PTA2, exhibited partial Agonist activity on the platelet and smooth muscle preparations. There was good agreement between absolute potencies on the six preparations; on platelets Potency was assessed from shape change measurements, since aggregation, when present, always showed a very shallow concentration-response relationship. The magnitude of the maximum response induced by each compound decreased in the order listed above, to the extent that 16,20-methano PTA2 could be treated as a pure antAgonist. 4 With U-46619 as Agonist, the pA2 values of seven antAgonists were found to be very similar on human and rat platelets. The Potency ranking was EP 169 > AH 23848 > EP 092 > ONO 11120 > EP 115 = 16,20-methano PTA2 > BM 13177. There was a similar trend on rabbit platelets but pA2 values were 1.0–1.5 log units smaller; the exception was BM 13177 which had similar affinities. The antagonism produced by EP 169 and AH 23848 was surmountable on rabbit platelets but not on human and rat platelets. 5 None of the antAgonists was highly potent on the rabbit aorta (pA2 values 0.05). 6 The excellent agreement for both full and partial Agonist potencies between the six preparations provides no evidence for TP-receptor subtypes and further suggests that the Agonist recognition sites of the TP-receptors could be very similar, if not identical, in nature. In contrast, the different antAgonist affinities found in this and other published studies indicate heterogeneity of TP-receptors. However, classification into TP1-, TP2-receptors, etc. on the basis of the limited antAgonist data available does not appear appropriate at this time.
Kevin V Thomas - One of the best experts on this subject based on the ideXlab platform.
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the stable aryl hydrocarbon receptor Agonist Potency of united kingdom continental shelf ukcs offshore produced water effluents
Marine Pollution Bulletin, 2005Co-Authors: Mark R Hurst, Yin L Chanman, Jan Balaam, John E Thain, Kevin V ThomasAbstract:Abstract The in vitro aryl hydrocarbon receptor (AhR) Agonist Potency of offshore produced water effluents, collected from the United Kingdom Continental Shelf, was determined using the dioxin responsive (DR)-chemically activated luciferase expression (CALUX) assay. Octadecylsilane (C18) solid phase extraction (SPE) extracts of produced water were exposed to DR-CALUX cells for 24 h in order to investigate the contribution in Potency from compounds that are stable to metabolism by the CALUX cells during exposure. The stable AhR Agonist Potency determined over 24 h was highly variable and ranged from 1 to 430 ng TCDD TEQCALUX l−1. These data reflect the highly variable composition of produced water discharges from different production fields. It is recommended that further work be performed to characterise the full range of stable dioxin like AhR Agonists present in offshore produced water discharges using techniques such as bioassay-directed analysis.
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Bio-analytical and chemical characterisation of offshore produced water effluents for estrogen receptor (ER) Agonists
Journal of Environmental Monitoring, 2004Co-Authors: Kevin V Thomas, Mark R Hurst, Jan Balaam, John E ThainAbstract:The in vitro estrogen receptor (ER) Agonist Potency and C1 to C9 alkyl substituted phenol content of offshore produced water effluents collected from the UK sector of the North Sea were determined using a combination of bio-analytical and chemical analysis techniques. An in vitro reporter gene assay was used to determine ER Agonist Potency, whilst gas chromatography coupled to mass spectrometry (GC-MS) was used to quantify the concentration of alkylphenols. The in vitro ER Agonist Potency was highly variable and ranged from less than the limit of detection (theoretically 0.03 ng 17β-estradiol (E2) l−1) to 91 ng E2 l−1. C1 to C5 alkylphenol concentrations were also highly variable ranging from 5 to 1600 μg l−1 with a median concentration of 206 μg l−1. These data reflect the highly variable composition of produced water discharges from different fields. The observed poor correlation of the alkylphenol isomer content and ER Agonist activity suggests that other compounds present in the produced water discharges may be responsible for the ER Agonist activity observed. It is recommended that further work be performed to characterise the full range of ER Agonists present in offshore produced water discharges.
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Identification of in vitro estrogen and androgen receptor Agonists in North Sea offshore produced water discharges
Environmental Toxicology and Chemistry, 2004Co-Authors: Kevin V Thomas, Mark R Hurst, Jan Balaam, John E ThainAbstract:The estrogen receptor (ER) Agonist Potency of offshore produced water discharges was examined via bioassay-directed chemical analysis. The in vitro estrogen receptor (ER) and androgen receptor (AR) Agonist Potency of five produced water samples collected from oil-production platforms in the British and Norwegian sectors of the North Sea was determined by using the yeast estrogen and androgen screens. Produced water samples were extracted in situ on the production platforms by using large-volume solid-phase extraction. All five extracts tested positive for the presence of ER Agonists, whereas no AR Agonist activity could be detected. By using the yeast estrogen screen assay in association with bioassay-directed fractionation, attempts were made to identify the ER Agonist compounds present in the produced water extracts. The fractionation procedure used cyano-amino-bonded silica normal-phase high-performance liquid chromatography to isolate estrogenic compounds from produced water extract followed by full-scan gas chromatography-electron-impact mass spectrometry (GC-(EI)MS) to identify them. Isomeric mixtures of C 1 to C 5 and C 9 alkylphenols contributed to the majority of the ER Agonist Potency measured in the samples.
