Effects of increasing hydrophobicity on the physical-chemical and biological properties of a class A amphipathic helical peptide
We have recently shown that a class A amphipathic peptide 5F with increased amphipathicity protected mice from diet-induced atherosclerosis (Garber et al. J. Lipid Res. 2001. 42: 545–552). We have now examined the effects of increasing the hydrophobicity of a series of homologous class A amphipathic...
| Main Authors: | , , , , , , , , , , , , |
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| Format: | Article |
| Language: | English |
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Elsevier
2001-07-01
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| Series: | Journal of Lipid Research |
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| Online Access: | http://www.sciencedirect.com/science/article/pii/S0022227520315996 |
| _version_ | 1818676082628362240 |
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| author | Geeta Datta Manjula Chaddha Susan Hama Mohamad Navab Alan M. Fogelman David W. Garber Vinod K. Mishra Richard M. Epand Raquel F. Epand Sissel Lund-Katz Michael C. Phillips Jere P. Segrest G.M. Anantharamaiah |
| author_facet | Geeta Datta Manjula Chaddha Susan Hama Mohamad Navab Alan M. Fogelman David W. Garber Vinod K. Mishra Richard M. Epand Raquel F. Epand Sissel Lund-Katz Michael C. Phillips Jere P. Segrest G.M. Anantharamaiah |
| author_sort | Geeta Datta |
| collection | DOAJ |
| description | We have recently shown that a class A amphipathic peptide 5F with increased amphipathicity protected mice from diet-induced atherosclerosis (Garber et al. J. Lipid Res. 2001. 42: 545–552). We have now examined the effects of increasing the hydrophobicity of a series of homologous class A amphipathic peptides, including 5F, on physical and functional properties related to atherosclerosis inhibition by systematically replacing existing nonpolar amino acids with phenylalanine. The peptides, based on the sequence Ac-D-W-L-K-A-F-Y-D-K-V-A-E-K-L-K-E-A-F-NH2 (Ac-18A-NH2 or 2F) were: 3F3(Ac-F318A-NH2), 3F14(Ac-F1418A-NH2), 4F(Ac-F3,1418A-NH2), 5F(Ac-F11,14,17 18A-NH2), 6F(Ac-F10,11,14,17 18A-NH2), and 7F(Ac-F3,10,11,14,17 18A-NH2). Measurements of aqueous solubility, HPLC retention time, exclusion pressure for penetration into an egg phosphatidylcholine (EPC) monolayer, and rates of EPC solubilization revealed an abrupt increase in the hydrophobicity between peptides 4F and 5F; this was accompanied by increased ability to associate with phospholipids. The peptides 6F and 7F were less effective, indicating a limit to increased hydrophobicity for promoting lipid interaction in these peptides. Despite this marked increase in lipid affinity, these peptides were less effective than apoA-I in activating the plasma enzyme, lecithin:cholesterol acyltransferase, with 5F activating LCAT the best (80% of apoA-I). Peptides 4F, 5F, and 6F were equally potent in inhibiting LDL-induced monocyte chemotactic activity.These studies suggest that an appropriate balance between peptide-peptide and peptide-lipid interactions is required for optimal biological activity of amphipathic peptides. These studies provide a rationale for the design of small apoA-I-mimetics with increased potency for atherosclerosis inhibition.—Datta, G., M. Chaddha, S. Hama, M. Navab, A. M. Fogelman, D. W. Garber, V. K. Mishra, R. M. Epand, R. F. Epand, S. Lund-Katz, M. C. Phillips, J. P. Segrest, and G. M. Anantharamaiah. Effects of increasing hydrophobicity on the physical-chemical and biological properties of a class A amphipathic helical peptide. J. Lipid Res. 2001. 42: 1096–1104. |
| first_indexed | 2024-12-17T08:37:49Z |
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| language | English |
| last_indexed | 2024-12-17T08:37:49Z |
| publishDate | 2001-07-01 |
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| series | Journal of Lipid Research |
| spelling | doaj.art-62fdf75385c94ccb9e705890571616b42022-12-21T21:56:26ZengElsevierJournal of Lipid Research0022-22752001-07-0142710961104Effects of increasing hydrophobicity on the physical-chemical and biological properties of a class A amphipathic helical peptideGeeta Datta0Manjula Chaddha1Susan Hama2Mohamad Navab3Alan M. Fogelman4David W. Garber5Vinod K. Mishra6Richard M. Epand7Raquel F. Epand8Sissel Lund-Katz9Michael C. Phillips10Jere P. Segrest11G.M. Anantharamaiah12The Atherosclerosis Research Unit and the Departments of Medicine and Biochemistry and Molecular Genetics, The University of Alabama at Birmingham Medical Center, Birmingham, AL 35294The Atherosclerosis Research Unit and the Departments of Medicine and Biochemistry and Molecular Genetics, The University of Alabama at Birmingham Medical Center, Birmingham, AL 35294The Atherosclerosis Research Unit, UCLA Cardiology, Los Angeles, CA 90095The Atherosclerosis Research Unit, UCLA Cardiology, Los Angeles, CA 90095The Atherosclerosis Research Unit, UCLA Cardiology, Los Angeles, CA 90095The Atherosclerosis Research Unit and the Departments of Medicine and Biochemistry and Molecular Genetics, The University of Alabama at Birmingham Medical Center, Birmingham, AL 35294The Atherosclerosis Research Unit and the Departments of Medicine and Biochemistry and Molecular Genetics, The University of Alabama at Birmingham Medical Center, Birmingham, AL 35294Department of Biochemistry, McMaster University, Health Sciences Center, Hamilton, Ontario, Canada L8N 3Z5Department of Biochemistry, McMaster University, Health Sciences Center, Hamilton, Ontario, Canada L8N 3Z5Stokes Research Institute, Children's Hospital of Philadelphia, Philadelphia, PA 19104Stokes Research Institute, Children's Hospital of Philadelphia, Philadelphia, PA 19104The Atherosclerosis Research Unit and the Departments of Medicine and Biochemistry and Molecular Genetics, The University of Alabama at Birmingham Medical Center, Birmingham, AL 35294To whom correspondence should be addressed.; The Atherosclerosis Research Unit and the Departments of Medicine and Biochemistry and Molecular Genetics, The University of Alabama at Birmingham Medical Center, Birmingham, AL 35294We have recently shown that a class A amphipathic peptide 5F with increased amphipathicity protected mice from diet-induced atherosclerosis (Garber et al. J. Lipid Res. 2001. 42: 545–552). We have now examined the effects of increasing the hydrophobicity of a series of homologous class A amphipathic peptides, including 5F, on physical and functional properties related to atherosclerosis inhibition by systematically replacing existing nonpolar amino acids with phenylalanine. The peptides, based on the sequence Ac-D-W-L-K-A-F-Y-D-K-V-A-E-K-L-K-E-A-F-NH2 (Ac-18A-NH2 or 2F) were: 3F3(Ac-F318A-NH2), 3F14(Ac-F1418A-NH2), 4F(Ac-F3,1418A-NH2), 5F(Ac-F11,14,17 18A-NH2), 6F(Ac-F10,11,14,17 18A-NH2), and 7F(Ac-F3,10,11,14,17 18A-NH2). Measurements of aqueous solubility, HPLC retention time, exclusion pressure for penetration into an egg phosphatidylcholine (EPC) monolayer, and rates of EPC solubilization revealed an abrupt increase in the hydrophobicity between peptides 4F and 5F; this was accompanied by increased ability to associate with phospholipids. The peptides 6F and 7F were less effective, indicating a limit to increased hydrophobicity for promoting lipid interaction in these peptides. Despite this marked increase in lipid affinity, these peptides were less effective than apoA-I in activating the plasma enzyme, lecithin:cholesterol acyltransferase, with 5F activating LCAT the best (80% of apoA-I). Peptides 4F, 5F, and 6F were equally potent in inhibiting LDL-induced monocyte chemotactic activity.These studies suggest that an appropriate balance between peptide-peptide and peptide-lipid interactions is required for optimal biological activity of amphipathic peptides. These studies provide a rationale for the design of small apoA-I-mimetics with increased potency for atherosclerosis inhibition.—Datta, G., M. Chaddha, S. Hama, M. Navab, A. M. Fogelman, D. W. Garber, V. K. Mishra, R. M. Epand, R. F. Epand, S. Lund-Katz, M. C. Phillips, J. P. Segrest, and G. M. Anantharamaiah. Effects of increasing hydrophobicity on the physical-chemical and biological properties of a class A amphipathic helical peptide. J. Lipid Res. 2001. 42: 1096–1104.http://www.sciencedirect.com/science/article/pii/S0022227520315996amphipathic α-helixapoA-I analogshydrophobicityLCATsynthetic peptidesmonocyte chemotactic activity |
| spellingShingle | Geeta Datta Manjula Chaddha Susan Hama Mohamad Navab Alan M. Fogelman David W. Garber Vinod K. Mishra Richard M. Epand Raquel F. Epand Sissel Lund-Katz Michael C. Phillips Jere P. Segrest G.M. Anantharamaiah Effects of increasing hydrophobicity on the physical-chemical and biological properties of a class A amphipathic helical peptide Journal of Lipid Research amphipathic α-helix apoA-I analogs hydrophobicity LCAT synthetic peptides monocyte chemotactic activity |
| title | Effects of increasing hydrophobicity on the physical-chemical and biological properties of a class A amphipathic helical peptide |
| title_full | Effects of increasing hydrophobicity on the physical-chemical and biological properties of a class A amphipathic helical peptide |
| title_fullStr | Effects of increasing hydrophobicity on the physical-chemical and biological properties of a class A amphipathic helical peptide |
| title_full_unstemmed | Effects of increasing hydrophobicity on the physical-chemical and biological properties of a class A amphipathic helical peptide |
| title_short | Effects of increasing hydrophobicity on the physical-chemical and biological properties of a class A amphipathic helical peptide |
| title_sort | effects of increasing hydrophobicity on the physical chemical and biological properties of a class a amphipathic helical peptide |
| topic | amphipathic α-helix apoA-I analogs hydrophobicity LCAT synthetic peptides monocyte chemotactic activity |
| url | http://www.sciencedirect.com/science/article/pii/S0022227520315996 |
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