PEPTIDE ATTACHMENT TO EXTREMITIES OF LIPOSOMAL SURFACE GRAFTED PEG CHAINS - PREPARATION OF THE LONG-CIRCULATING FORM OF LAMININ PENTAPEPTIDE, YIGSR

被引:63
作者
ZALIPSKY, S
PUNTAMBEKAR, B
BOULIKAS, P
ENGBERS, CM
WOODLE, MC
机构
[1] SEQUUS Pharmaceuticals, Inc, California, 960 Hamilton Court, Menlo Park
[2] Genta, Inc, 3550 General Atomics Ct, California, San Diego
关键词
D O I
10.1021/bc00036a008
中图分类号
Q5 [生物化学];
学科分类号
071010 ; 081704 ;
摘要
Poly(ethylene glycol) (PEG)-grafted liposomes offer new opportunities as long-circulating platforms presenting biologically relevant ligands. In pursuit of this goal, liposomal conjugates of YIGSR were prepared by mild periodate oxidation of TYIGSR-NH2 and incubation of the product with hydrazide-PEG-(distearoylphosphatidyl)ethanol amine-containing liposomes. The peptide-carrying liposomes, with up to 500 YIGSR residues per vesicle, despite exhibiting faster blood clearance rates than the parent liposomes in rats, remained in circulation for extended periods of time. Mean residence times for the parent liposomal formulation and conjugated preparations containing 200 and 500 YIGSR residues per vesicle were 28, 25, and 23 h, respectively. The results have important implications for systemic delivery of peptides and for their use as targeting moieties for PEG-grafted liposomes.
引用
收藏
页码:705 / 708
页数:4
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