Design, synthesis, and evaluation of heparan sulfate mimicking glycopolymers for inhibiting heparanase activity

被引:37
|
作者
Loka, Ravi S. [1 ]
Yu, Fei [1 ]
Sletten, Eric T. [1 ]
Nguyen, Hien M. [1 ]
机构
[1] Univ Iowa, Dept Chem, Iowa City, IA 52242 USA
关键词
TUMOR-GROWTH; ANGIOGENESIS; EXPRESSION; BINDING; AGGLUTINATION; PROTEOGLYCANS; METASTASIS; MIMETICS; RELEASE; CANCER;
D O I
10.1039/c7cc04156j
中图分类号
O6 [化学];
学科分类号
0703 ;
摘要
Heparanase is an enzyme which cleaves heparan sulfate (HS) polysaccharides of the extracellular matrix. It is a regulator of tumor behavior, plays a key role in kidney related diseases and autoimmune diabetes. We report herein the use of computational studies to extract the natural HS-heparanase interactions as a template for the design of HS mimicking glycopolymers. Upon evaluation, a glycopolymer with 12 repeating units was determined to be the most potent inhibitor and to have tight-binding characteristics. This glycopolymer also lacks anticoagulant activity.
引用
收藏
页码:9163 / 9166
页数:4
相关论文
共 50 条
  • [1] Synthesis of a Heparan Sulfate Disaccharide Fluoride for Detection of Heparanase Activity
    Ohmae, Masashi
    Fujita, Yuki
    Takada, Junko
    Kimura, Shunsaku
    CHEMISTRY LETTERS, 2013, 42 (10) : 1168 - 1169
  • [2] Heparanase 2 Interacts with Heparan Sulfate with High Affinity and Inhibits Heparanase Activity
    Levy-Adam, Flonia
    Feld, Sari
    Cohen-Kaplan, Victoria
    Shteingauz, Anna
    Gross, Miriam
    Arvatz, Gil
    Naroditsky, Inna
    Ilan, Neta
    Doweck, Ilana
    Vlodavsky, Israel
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2010, 285 (36) : 28010 - 28019
  • [3] Synthesis of novel S- and O-disaccharide analogs of heparan sulfate for heparanase inhibition
    Teki, D. S-E Koffi
    Coulibaly, B.
    Bil, A.
    Vallin, A.
    Lesur, D.
    Fante, B.
    Chagnault, V
    Kovensky, J.
    ORGANIC & BIOMOLECULAR CHEMISTRY, 2022, 20 (17) : 3528 - 3534
  • [4] Heparan Sulfate Containing Unsubstituted Glucosamine Residues BIOSYNTHESIS AND HEPARANASE-INHIBITORY ACTIVITY
    Nadanaka, Satomi
    Purunomo, Eko
    Takeda, Naoko
    Tamura, Jun-ichi
    Kitagawa, Hiroshi
    JOURNAL OF BIOLOGICAL CHEMISTRY, 2014, 289 (22) : 15231 - 15243
  • [5] The Uptake of Heparanase into Mast Cells Is Regulated by Its Enzymatic Activity to Degrade Heparan Sulfate
    Shi, Jia
    Onuki, Yoshiki
    Kawanami, Fumiya
    Miyagawa, Naoko
    Iwasaki, Fumika
    Tsuda, Haruna
    Takahashi, Katsuhiko
    Oku, Teruaki
    Suzuki, Masato
    Higashi, Kyohei
    Adachi, Hayamitsu
    Nishimura, Yoshio
    Nakajima, Motowo
    Irimura, Tatsuro
    Higashi, Nobuaki
    INTERNATIONAL JOURNAL OF MOLECULAR SCIENCES, 2024, 25 (11)
  • [6] Modular Synthesis of Heparan Sulfate Oligosaccharides for Structure-Activity Relationship Studies
    Arungundram, Sailaja
    Al-Mafraji, Kanar
    Asong, Jinkeng
    Leach, Franklin E., III
    Amster, I. Jonathan
    Venot, Andre
    Turnbull, Jeremy E.
    Boons, Geert-Jan
    JOURNAL OF THE AMERICAN CHEMICAL SOCIETY, 2009, 131 (47) : 17394 - 17405
  • [7] Heparan Sulfate Mimicking Glycopolymer Prevents Pancreatic β Cell Destruction and Suppresses Inflammatory Cytokine Expression in Islets under the Challenge of Upregulated Heparanase
    Loka, Ravi S.
    Song, Zhenfeng
    Sletten, Eric T.
    Kayal, Yasmin
    Vlodavsky, Israel
    Zhang, Kezhong
    Nguyen, Hien M.
    ACS CHEMICAL BIOLOGY, 2022, 17 (06) : 1387 - 1400
  • [8] Heparan Sulfate-Mimicking Glycopolymers Bind SARS-CoV-2 Spike Protein in a Length- and Sulfation Pattern-Dependent Manner
    Abdulsalam, Hawau
    Li, Jiayi
    Loka, Ravi S.
    Sletten, Eric T.
    Nguyen, Hien M.
    ACS MEDICINAL CHEMISTRY LETTERS, 2023, 14 (10): : 1411 - 1418
  • [9] Design and Synthesis of 6-O-Phosphorylated Heparan Sulfate Oligosaccharides to Inhibit Amyloid β Aggregation
    Uchimura, Kenji
    Nishitsuji, Kazuchika
    Chiu, Li-Ting
    Ohgita, Takashi
    Saito, Hiroyuki
    Allain, Fabrice
    Gannedi, Veeranjaneyulu
    Wong, Chi-Huey
    Hung, Shang-Cheng
    CHEMBIOCHEM, 2022, 23 (15)
  • [10] In vitro evaluation of the antiviral activity of heparan sulfate mimetic compounds against Enterovirus 71
    Pourianfar, Hamid Reza
    Poh, Chit Laa
    Fecondo, John
    Grollo, Lara
    VIRUS RESEARCH, 2012, 169 (01) : 22 - 29