当前位置： SCI文献检索 > BIOORGANIC & MEDICINAL CHEMISTRY期刊下所有文献 > Intestinal absorption of fluorescence-derivatized cationic peptide 001-C8-NBD via adsorptive-mediated transcytosis.

Intestinal absorption of fluorescence-derivatized cationic peptide 001-C8-NBD via adsorptive-mediated transcytosis.

Abstract：

:The intestinal absorption of an intact oligopeptide was investigated in rats using a synthetic cationic peptide, 001-C8 (H-MeTyr-Arg-MeArg-D-Leu-NH(CH2)8NH2). The peptide was coupled with 4-nitrobenzo-2-oxa-1,3-diazole (NBD) to prepare a fluorescence-labeled derivative 001-C8-NBD (H-MeTyr-Arg-MeArg-D-Leu-NH(CH2)8NH-NBD) for the purpose of quantification. The degradation half-life of 001-C8-NBD in jejunal homogenate (1 mg/mL) was 99.5 min, which was significantly longer than that of natural leucine enkephalin (1.14 min). The absorption of 001-C8-NBD was evaluated by the vascular-perfusion method. Intact 001-C8-NBD appeared in the blood time-dependently and the absorption volume at 30 min (2.75 +/- 0.14 microL/cm intestine) was significantly larger than that of [3H]PEG 900 (0.88 +/- 0.13 microL/cm intestine), of which membrane permeability is very low. The absorption of 001-C8-NBD was greatly reduced by an adsorptive-mediated endocytosis inhibitor, protamine (10 mM). No inhibition of the absorption of [3H]PEG 900 by protamine was observed. The intestinal absorption was also measured by an in vivo loop method. The absorption clearance of 001-C8-NBD measured by this method (0.083 +/- 0.008 microL/min/cm intestine) was comparable to that obtained by the vascular perfusion method (0.092 +/- 0.005 microL/min/cm intestine). All of these data suggested that 001-C8-NBD was absorbed as the intact oligopeptide in the intestine in vivo. Adsorptive-mediated transcytosis is suggested to have enormous potential as an oral delivery system for peptide and/or protein drugs.

journal_name

Bioorg Med Chem

journal_title

Bioorganic & medicinal chemistry

authors

Sai Y,Kajita M,Tamai I,Kamata M,Wakama J,Wakamiya T,Tsuji A

doi

10.1016/s0968-0896(98)00031-5

subject

Has Abstract

pub_date

1998-06-01 00:00:00

pages

841-8

issue

6

eissn

0968-0896

issn

1464-3391

pii

S0968-0896(98)00031-5

journal_volume

6

pub_type

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