Isolation and identification of inhibitors against matrix metallo proteinase in shark cartilage

鲨鱼软骨基质金属蛋白酶抑制剂的分离与鉴定

• 批准号: 11660208
• 负责人: SATO Kenji
• 金额: $ 2.05万
• 依托单位: Kyoto Prefectural University
• 依托单位国家: 日本
• 项目类别: Grant-in-Aid for Scientific Research (C)
• 财政年份: 1999
• 资助国家: 日本
• 起止时间: 1999 至 2000
• 项目状态: 已结题
• 来源: https://kaken.nii.ac.jp/grant/KAKENHI-PROJECT-11660208/
• 关键词: Shark; MMP; Inhibitor; Collagenase; Gelatinase; Muco polysaccharide; MMP-9; Cancer; マトリックスメタロプロテアーゼ; サメ; 軟骨; 多糖類; Autofocusing

Matrix metallo proteinases (MMP), especially MMP-9 plays a significant role in invasion and metastasis of cancer. An objective of the present research project is to isolate and identify the material having the inhibitory activity against MMP-9. The crude water-extract of dried shark fin had an inhibitory activity against MMP-9. The activity was concentrated into an acidic fraction by preparative isoelectric focusing in the absence of added ampholyte. In addition, it was recovered in the non-adsorbed fraction of the reversed-phase HPLC and void volume fraction of the size exclusion chromatography. A compositional analysis revealed that it consists of uronic acid and galactsamine. These facts indicate that the acidic muco polysacchmide in the shark cartilage has the inhibitory activity against MMP-9. Then the activity can be easily concentrated as an ethanol (75%) insoluble fraction of the water extract. Now therapeutic effect of the ethanol insoluble fraction by oral administration is examined by using an animal model, chemically-induced pancreatic cancer in hamster.

基质金属蛋白酶(MMP)，特别是MMP-9在癌症的侵袭和转移中发挥着重要作用。本研究项目的一个目的是分离和鉴定对MMP-9具有抑制活性的材料。干鱼翅粗水提物对MMP-9有抑制活性。在不添加两性电解质的情况下，通过制备型等电聚焦将活性浓缩成酸性级分。另外，在反相HPLC的非吸附级分和尺寸排阻色谱法的空隙体积级分中进行了回收。成分分析表明它由糖醛酸和半乳糖胺组成。这些事实表明，鲨鱼软骨中的酸性粘膜多糖具有对MMP-9的抑制活性。然后，活性可以很容易地浓缩为水提取物的乙醇（75%）不溶部分。现在，通过使用化学诱导的仓鼠胰腺癌动物模型来检查口服乙醇不溶性级分的治疗效果。

项目成果

Asuka Akahoshi, Kenji Sato, Yuko Nawa, Yasushi Nakamura, and Kozo Ohtsuki: "A Novel Approach for Large Scale, Biocompatible and Low Cost Fractionation of Peptides in Proteolytic Digest of Food Protein on the Basis of Amphoteric Nature of Peptides."Jourana

Asuka Akahoshi、Kenji Sato、Yuko Nawa、Yasushi Nakamura 和 Kozo Ohtsuki：“基于肽的两性性质，在食物蛋白的蛋白水解消化中对肽进行大规模、生物相容性和低成本分级的新方法。”Jourana

Asuka Akahoshi, Kenji Sato, Yuko Nawa, Yaushi Nakamura, Kozo Ohtsuki,: "A novel approach for largo scalo, biocompatiblo and low cost fractionation of peptide In proteolytic digoat of food protein on the basis of amphoteric nature of peptide"Journal of Agr

Asuka Akahoshi、Kenji Sato、Yuko Nawa、Yaushi Nakamura、Kozo Ohtsuki，：“基于肽的两性性质，在食品蛋白的蛋白水解双山羊中实现肽的大尺度、生物相容性和低成本分馏的新方法”农业杂志

赤星亜寿香: "Novel approach for large-scale, biocompatible, and low-cost fractionation of peptides in proteolytic digest of food protein based on the amphoteric nature of peptides"J.Agric.Food.Chem.. 48・5. 1955-1959 (2000)

Asuka Akahoshi：“基于肽的两性性质，在食品蛋白质的蛋白水解消化中对肽进行大规模、生物相容性和低成本分级的新方法”J.Agric.Food.Chem.. 1955-1959。 (2000)

赤星亜寿香: "Novel approach for large-scale, biocompatible, and low-cost fractionation of peptides in proteolytic digest of food protein based on the amphoteric nature of peptides"J.Agric Food Chem.. 48・5. 1955-1959 (2000)

Asuka Akahoshi：“基于肽的两性性质，在食品蛋白的蛋白水解消化中对肽进行大规模、生物相容性和低成本分级的新方法”J.Agric Food Chem.. 1955-1959 (2000) ）