Renal drug targeting using a vector "alkylglycoside".

体内 化学 加压素 超滤(肾) 生物化学 药理学 立体化学 内分泌学 生物 生物技术
作者
Kokichi Suzuki,H Susaki,Satoshi Okuno,Yuichi Sugiyama
出处
期刊:PubMed 卷期号:288 (1): 57-64 被引量:36
链接
标识
摘要

A specific sugar-modified peptide has previously been shown to have renal targeting potential in vivo and to have a specific binding site which has been identified in the kidney membrane fraction. In this report, we studied the inhibitory effects of glycosylated derivatives on the binding of [3H]Glc-O-C8-AVP [a glucosylated derivative of Arg8-vasopressin (AVP), Kd = 55 nM] to clarify the structural requirements necessary for renal recognition. Glc-S-C7-Me (octyl beta-D-thioglucoside) markedly inhibited the binding, to a much greater extent than Glc-O-C7-Me (octyl beta-D-glucoside) and Gal-S-C7-Me (octyl beta-D-thiogalactoside). Also, [3H]Glc-S-C7-Me was shown to have a specific binding site on the kidney membrane (Kd = 17 nM, Bmax = 24 pmol/mg protein) rather than the liver membrane and, in addition, Glc-S-C7-Me exhibited effective and selective renal uptake in vivo. To examine the possibility that Glc-S-C7-Me might be of practical use as a renal targeting vector, AVP, tryptamine and 4-nitrobenz-2-oxa-1,3-diazole were modified with Glc-S-C8- and the tissue uptake of the resulting derivatives was evaluated. All of these derivatives showed clear renal targeting potential because the apparent uptake clearance by the kidney was greater than 3 ml/min/g kidney in each case. As far as the AVP derivatives were concerned, derivatives having different numbers of methylene groups were compared with Glc-S-C8-AVP. Glc-S-C11-AVP exhibited increased kidney targeting potential, whereas that of Glc-S-C5-AVP was reduced. These differences suggest that the "alkylglycoside" moiety is important for renal uptake. In addition, these renally targeted derivatives inhibited the binding of [3H]Glc-S-C7-Me to the kidney membrane fraction. Our findings allow us to conclude that the alkylglycoside is a suitable candidate vector for renal targeting.

科研通智能强力驱动
Strongly Powered by AbleSci AI
更新
PDF的下载单位、IP信息已删除 (2025-6-4)

科研通是完全免费的文献互助平台,具备全网最快的应助速度,最高的求助完成率。 对每一个文献求助,科研通都将尽心尽力,给求助人一个满意的交代。
实时播报
xd完成签到,获得积分10
刚刚
1秒前
somnus发布了新的文献求助10
1秒前
reirei应助过时的冰棍采纳,获得10
2秒前
茶荼完成签到,获得积分10
3秒前
3秒前
量子星尘发布了新的文献求助10
4秒前
琥斛完成签到 ,获得积分10
5秒前
雨晨完成签到,获得积分10
6秒前
7秒前
JK157完成签到,获得积分10
9秒前
Heartlark发布了新的文献求助10
9秒前
li完成签到,获得积分0
9秒前
10秒前
今后应助gsonix采纳,获得10
10秒前
Dritsw应助shiko采纳,获得10
11秒前
12秒前
流动中的小孩完成签到,获得积分10
12秒前
砍柴少年发布了新的文献求助10
13秒前
czt完成签到 ,获得积分10
14秒前
干净盼山完成签到,获得积分10
15秒前
PhD完成签到,获得积分10
17秒前
Jing发布了新的文献求助10
17秒前
小崔发布了新的文献求助10
17秒前
18秒前
大型海狮完成签到,获得积分10
18秒前
舒心谷雪完成签到 ,获得积分10
22秒前
22秒前
23秒前
yang发布了新的文献求助10
23秒前
Jing完成签到,获得积分10
24秒前
24秒前
check003完成签到,获得积分10
25秒前
27秒前
27秒前
27秒前
智慧女孩发布了新的文献求助10
27秒前
叶叶叶发布了新的文献求助10
27秒前
28秒前
Ava应助yang采纳,获得10
28秒前
高分求助中
A new approach to the extrapolation of accelerated life test data 1000
Cognitive Neuroscience: The Biology of the Mind 1000
Technical Brochure TB 814: LPIT applications in HV gas insulated switchgear 1000
Toward a Combinatorial Approach for the Prediction of IgG Half-Life and Clearance 500
ACSM’s Guidelines for Exercise Testing and Prescription, 12th edition 500
Picture Books with Same-sex Parented Families: Unintentional Censorship 500
Nucleophilic substitution in azasydnone-modified dinitroanisoles 500
热门求助领域 (近24小时)
化学 材料科学 医学 生物 工程类 有机化学 生物化学 物理 内科学 纳米技术 计算机科学 化学工程 复合材料 遗传学 基因 物理化学 催化作用 冶金 细胞生物学 免疫学
热门帖子
关注 科研通微信公众号,转发送积分 3969917
求助须知:如何正确求助?哪些是违规求助? 3514626
关于积分的说明 11175060
捐赠科研通 3249928
什么是DOI,文献DOI怎么找? 1795165
邀请新用户注册赠送积分活动 875617
科研通“疑难数据库(出版商)”最低求助积分说明 804891