کد مقاله | کد نشریه | سال انتشار | مقاله انگلیسی | نسخه تمام متن |
---|---|---|---|---|
10748343 | 1050271 | 2016 | 6 صفحه PDF | دانلود رایگان |
عنوان انگلیسی مقاله ISI
Amphipathic polyproline peptides stimulate cholesterol efflux by the ABCA1 transporter
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کلمات کلیدی
HDLABCA1BHKATP-binding cassette transporter A1 - ATP اتصال گیرنده کاست A1cardiovascular disease - بیماری قلب و عروقیlow density lipoproteins - لیپوپروتئین های چگالی کمLDL - لیپوپروتئین کم چگالی(کلسترول بد)high density lipoproteins - لیپوپروتئینهای چگالی بالاpolyethylene glycol - پلی اتیلن گلیکولPEG - پلیاتیلن گلیکول Peptides - پپتیدهاcholesterol - کلسترول
موضوعات مرتبط
علوم زیستی و بیوفناوری
بیوشیمی، ژنتیک و زیست شناسی مولکولی
زیست شیمی
پیش نمایش صفحه اول مقاله
چکیده انگلیسی
ApoA-I mimetics are short synthetic peptides that contain an amphipathic α-helix and stimulate cholesterol efflux by the ABCA1 transporter in a detergent-like extraction mechanism. We investigated the use of amphipathic peptides with a polypro helix for stimulating cholesterol efflux by ABCA1. Polypro peptides were synthesized with modified prolines, containing either a hydrophobic phenyl group (Prop) or a polar N-acetylgalactosamine (Prog) attached to the pyrrolidine ring and were designated as either PP-2, 3, 4, or 5, depending on the number of 3 amino acid repeat units (Prop-Prog-Prop). Based on molecular modeling, these peptides were predicted to be relatively rigid and to bind to a phospholipid bilayer. By CD spectroscopy, PP peptides formed a Type-II polypro helix in an aqueous solution. PP-2 was inactive in promoting cholesterol efflux, but peptides with more than 2 repeat units were active. PP-4 showed a similar Vmax as a much longer amphipathic α-helical peptide, containing 37 amino acids, but had a Km that was approximately 20-fold lower. PP peptides were specific in that they did not stimulate cholesterol efflux from cells not expressing ABCA1 and were also non-cytotoxic. Addition of PP-3, 4 and 5 to serum promoted the formation of smaller size HDL species (7 nM) and increased its capacity for ABCA1-dependent cholesterol efflux by approximately 20-35% (p < 0.05). Because of their relatively small size and increased potency, amphipathic peptides with a polypro helix may represent an alternative structural motif for the development of apoA-I mimetic peptides.
ناشر
Database: Elsevier - ScienceDirect (ساینس دایرکت)
Journal: Biochemical and Biophysical Research Communications - Volume 471, Issue 4, 18 March 2016, Pages 560-565
Journal: Biochemical and Biophysical Research Communications - Volume 471, Issue 4, 18 March 2016, Pages 560-565
نویسندگان
D.O. Sviridov, S.K. Drake, L.A. Freeman, A.T. Remaley,