Targeting Human CD22/Siglec-2 with Dimeric Sialosides as Novel Oligosaccharide Mimetics

被引：6

作者：

Prescher, Horst ^{[2
]}

Schweizer, Astrid ^{[1
]}

Frank, Martin

Kuhfeldt, Elena ^{[2
]}

Ring, Julia ^{[1
]}

Nitschke, Lars ^{[1
]}

机构：

[1] Univ Erlangen Nurnberg, Chair Genet, Dept Biol, D-91058 Erlangen, Germany

[2] G3 BioTec, D-69207 Sandhausen, Germany

来源：

JOURNAL OF MEDICINAL CHEMISTRY | 2022年

关键词：

B-CELL LYMPHOMA; SIALIC-ACID; LIGAND-BINDING; CD22; LIGANDS; SIGLEC INHIBITORS; MOLECULE CD22; CIS LIGANDS; RECEPTOR; RECOGNITION; ANTIGEN;

D O I：

10.1021/acs.jmedchem.2c00765

中图分类号：

R914 [药物化学];

学科分类号：

100701 ;

摘要：

Significant interest in the development of high affinity ligands for Siglecs exists due to the various therapeutically relevant functions of these proteins. Here, we report a new strategy to develop and design Siglec ligands as disialyl-oligosaccharide mimetics exemplified on Siglec-2 (CD22). We report insights into development of dimeric ligands with high affinity and avidity to cell surface-expressed CD22, assay development, tool compounds, structure activity relationships, and biological data on calcium flux regulation in B-cells. The binding modes of selected ligands have been modeled based on state-of-the-art molecular dynamics simulations on the microsecond timescale, providing detailed views on ligand binding and opening a new perspective on drug design efforts for Siglecs. High-avidity dimeric ligands containing a linker opening the way towards bispecifics are presented as well.

引用

页码：10588 / 10610

页数：23

共 93 条

[1] Design, synthesis and molecular docking study of α-triazolylsialosides as non-hydrolyzable and potent CD22 ligands [J].

Abdu-Allah, Hajjaj H. M. ;

Wu, Shang-Chuen ;

Lin, Chun-Hung ;

Tseng, Yu-Yao .

EUROPEAN JOURNAL OF MEDICINAL CHEMISTRY, 2020, 208

[2] Design and Synthesis of a Multivalent Heterobifunctional CD22 Ligand as a Potential Immunomodulator [J].

Abdu-Allah, Hajjaj H. M. ;

Watanabe, Kozo ;

Daikoku, Shusaku ;

Kanie, Osamu ;

Tsubata, Takeshi ;

Ando, Hiromune ;

Ishida, Hideharu ;

Kiso, Makoto .

SYNTHESIS-STUTTGART, 2011, (18) :2968-2974

[3] CD22-Antagonists with nanomolar potency: The synergistic effect of hydrophobic groups at C-2 and C-9 of sialic acid scaffold [J].

Abdu-Allah, Hajjaj H. M. ;

Watanabe, Kozo ;

Completo, Gladys C. ;

Sadagopan, Magesh ;

Hayashizaki, Koji ;

Takaku, Chiaki ;

Tamanaka, Taichi ;

Takematsu, Hiromu ;

Kozutsumi, Yasunori ;

Paulson, James C. ;

Tsubata, Takeshi ;

Ando, Hiromune ;

Ishida, Hideharu ;

Kiso, Makoto .

BIOORGANIC & MEDICINAL CHEMISTRY, 2011, 19 (06) :1966-1971

[4] Potent small molecule mouse CD22-inhibitors: Exploring the interaction of the residue at C-2 of sialic acid scaffold [J].

Abdu-Allah, Hajjaj H. M. ;

Watanabe, Kozo ;

Hayashizaki, Koji ;

Takaku, Chiaki ;

Tamanaka, Taichi ;

Takematsu, Hiromu ;

KozutsumiE, Yasunori ;

Tsubata, Takeshi ;

IshidaA, Hideharu ;

Kiso, Makoto .

BIOORGANIC & MEDICINAL CHEMISTRY LETTERS, 2009, 19 (19) :5573-5575

[5] Design, Synthesis, and Structure-Affinity Relationships of Novel Series of Sialosides as CD22-Specific Inhibitors [J].

Abdui-Allah, Hajaj H. M. ;

Tainanaka, Taichi ;

Yu, Jie ;

Zhuoyuan, Lu ;

Sadagopan, Magesh ;

Adachi, Takahiro ;

Tslibata, Takeshi ;

Kelm, Soerge ;

Ishida, Hideharu ;

Kiso, Makoto .

JOURNAL OF MEDICINAL CHEMISTRY, 2008, 51 (21) :6665-6681

[6] High resolution crystal structures of Siglec-7 - Insights into ligand specificity in the Siglec family [J].

Alphey, MS ;

Attrill, H ;

Crocker, PR ;

van Aalten, DMF .

JOURNAL OF BIOLOGICAL CHEMISTRY, 2003, 278 (05) :3372-3377

[7] A CD22-Shp1 phosphatase axis controls integrin β7 display and B cell function in mucosal immunity [J].

Ballet, Romain ;

Brennan, Martin ;

Brandl, Carolin ;

Feng, Ningguo ;

Berri, Jeremy ;

Cheng, Julian ;

Ocon, Borja ;

Sheikh, Amin Alborzian Deh ;

Marki, Alex ;

Bi, Yuhan ;

Abram, Clare ;

Lowell, Clifford .

FASEB JOURNAL, 2021, 35

[8] Bright oligothiophene N-succinimidyl esters for efficient fluorescent labeling of proteins and oligonucleotides [J].

Barbarella, G ;

Zambianchi, M ;

Ventola, A ;

Fabiano, E ;

Della Sala, F ;

Gigli, G ;

Anni, M ;

Bolognesi, A ;

Polito, L ;

Naldi, M ;

Capobianco, M .

BIOCONJUGATE CHEMISTRY, 2006, 17 (01) :58-67

[9] Exploiting CD22 To Selectively Tolerize Autoantibody Producing B-Cells in Rheumatoid Arthritis [J].

Bednar, Kyle J. ;

Nycholat, Corwin M. ;

Rao, Tadimeti S. ;

Paulson, James C. ;

Fung-Leung, Wai-Ping ;

Macauley, Matthew S. .

ACS CHEMICAL BIOLOGY, 2019, 14 (04) :644-654

[10] Siglecs: A journey through the evolution of sialic acid-binding immunoglobulin-type lectins [J].

Bornhoefft, Kim F. ;

Goldammer, Tom ;

Rebl, Alexander ;

Galuska, Sebastian P. .

DEVELOPMENTAL AND COMPARATIVE IMMUNOLOGY, 2018, 86 :219-231

← 1 2 3 4 5 6 7 8 9 10 →