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Synthesis of a novel lipopeptide with α-melanocyte-stimulating hormone peptide ligand and its effect on liposome stability

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Lipids

Abstract

Introduction of liposomes into target cells is important for drug delivery systems. For this purpose, the surface of the liposome is equipped with ligand peptides, which may bind to specific receptors on the cell membrane. An artificial novel lipopeptide (MSH-C4A2) containing the α-melanocyte-stimulating hormone (α-MSH) sequence and two long alkyl chains was designed and synthesized, and the liposome, composed of egg phosphatidylcholine (EPC) and MSH-C4A2, was prepared. The stability of the liposome was estimated by measuring calcein leakage from the liposome inner phase. The stability of the liposome decreased upon addition of MSH-A4C2, which seemed to be attributable to the amphiphilic property of the peptide moiety (α-MSH) of MSH-A2C4. The stability was, however, recovered fairly well upon addition of cholesterol (Ch) or phosphatidylglycerol (PG). It was concluded therefore that the ternary system, MSH-C4A2/Ch/EPC or MSH-C4A2/PG/EPC, is suitable for preparing the functional liposome.

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Abbreviations

Ch:

5-cholesten-3β-ol (cholesterol)

DDS:

drug delivery system

DMAP:

4-dimethylaminopyridine

DMF:

dimethylformamide

EPC:

egg phosphatidylcholine hydrogenated

FAB:

fast-atom bombardment

Fmoc:

N-α-9-fluorenylmethoxycarbonyl

HOBt:

1-hydroxybenzotriazole

MS:

mass spectrometry

α-MSH:

α-melanocyte-stimulating hormone

NMR:

nuclear magnetic resonance

PG:

1,2-dipalmitoyl-sn-glycero-3-[phospho-rac-(1-glycerol)] sodium salt (phosphatidylglycerol)

TBTU:

2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate

TFA:

trifluoroacetic acid

WSCI:

1-ethyl-3-(3-dimethylaminopropyl)-carbodiimide hydrochloride

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Authors and Affiliations

  1. Faculty of Industrial Science and Technology, Science University of Tokyo, 278-0022, Chiba, Japan

    Hidehiko Kawahara, Nobuhiro Yagi & Takeo Konakahara

  2. Biomolecules Department, National Institute of Bioscience and Human-Technology, 1-1 Higashi, 305-8566, Tsukuba, Ibarak, Japan

    Yoshikatsu Ogawa, Hidehiko Kawahara, Nobuhiro Yagi, Masato Kodaka, Takenori Tomohiro, Tomoko Okada & Hiroaki Okuno

Authors
  1. Yoshikatsu Ogawa
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  2. Hidehiko Kawahara
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  3. Nobuhiro Yagi
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  4. Masato Kodaka
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  5. Takenori Tomohiro
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  6. Tomoko Okada
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  7. Takeo Konakahara
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  8. Hiroaki Okuno
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Correspondence to Masato Kodaka.

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Ogawa, Y., Kawahara, H., Yagi, N. et al. Synthesis of a novel lipopeptide with α-melanocyte-stimulating hormone peptide ligand and its effect on liposome stability. Lipids 34, 387–394 (1999). https://doi.org/10.1007/s11745-999-0377-5

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  • DOI: https://doi.org/10.1007/s11745-999-0377-5

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