Functionalized High Mannose-Specific Lectins for the Discovery of Type I Mannosidase Inhibitors

Overview

Journal Angew Chem Int Ed Engl

Specialty Chemistry

Date 2021 Mar 17

PMID 33728787

Citations 4

Authors

Suresh E Kurhade

Jack D Weiner

Fei Philip Gao

Mark P Farrell

Affiliations

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Abstract

An engineered cyanovirin-N homologue that exhibits specificity for high mannose N-glycans has been constructed to aid type I α 1,2-mannosidase inhibitor discovery and development. Engineering the lectins C-terminus permitted facile functionalization with fluorophores via a sortase and click strategy. The resulting lectin constructs exhibit specificity for cells presenting high mannose N-glycans. Importantly, these lectin constructs can also be applied to specifically assess changes in cell surface glycosylation induced by type I mannosidase inhibitors. Testing the utility of these lectin constructs led to the discovery of type I mannosidase inhibitors with nanomolar potency. Cumulatively, these findings reveal the specificity and utility of the functionalized cyanovirin-N homologue constructs, and highlight their potential in analytical contexts that require high mannose-specific lectins.

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References

Wang H, Wu J, Gai J, Yang S, Ma Q, Ma H . MAN1B1 is associated with poor prognosis and modulates proliferation and apoptosis in bladder cancer. Gene. 2018; 679:314-319. DOI: 10.1016/j.gene.2018.09.022. View

Inoue N, Ikawa M, Okabe M . Putative sperm fusion protein IZUMO and the role of N-glycosylation. Biochem Biophys Res Commun. 2008; 377(3):910-4. DOI: 10.1016/j.bbrc.2008.10.073. View

Matei E, Basu R, Furey W, Shi J, Calnan C, Aiken C . Structure and Glycan Binding of a New Cyanovirin-N Homolog. J Biol Chem. 2016; 291(36):18967-76. PMC: 5009269. DOI: 10.1074/jbc.M116.740415. View

Dai X, Boker A, Glebe U . Broadening the scope of sortagging. RSC Adv. 2022; 9(9):4700-4721. PMC: 9060782. DOI: 10.1039/c8ra06705h. View

Hamester F, Legler K, Wichert B, Kelle N, Eylmann K, Rossberg M . Prognostic relevance of the Golgi mannosidase MAN1A1 in ovarian cancer: impact of N-glycosylation on tumour cell aggregation. Br J Cancer. 2019; 121(11):944-953. PMC: 6889143. DOI: 10.1038/s41416-019-0607-2. View

Chen H, Li R, Liu Z, Wei S, Zhang H, Li X . Synthesis of kifunensine thioanalogs and their inhibitory activities against HIV-RT and α-mannosidase. Carbohydr Res. 2012; 365:1-8. DOI: 10.1016/j.carres.2012.10.017. View

Iwami M, Nakayama O, Terano H, Kohsaka M, Aoki H, Imanaka H . A new immunomodulator, FR-900494: taxonomy, fermentation, isolation, and physico-chemical and biological characteristics. J Antibiot (Tokyo). 1987; 40(5):612-22. DOI: 10.7164/antibiotics.40.612. View

Helenius A, Aebi M . Intracellular functions of N-linked glycans. Science. 2001; 291(5512):2364-9. DOI: 10.1126/science.291.5512.2364. View

Shenoy S, Barrientos L, Ratner D, OKeefe B, Seeberger P, Gronenborn A . Multisite and multivalent binding between cyanovirin-N and branched oligomannosides: calorimetric and NMR characterization. Chem Biol. 2002; 9(10):1109-18. DOI: 10.1016/s1074-5521(02)00237-5. View

10.

Hering K, Karaveg K, Moremen K, Pearson W . A practical synthesis of kifunensine analogues as inhibitors of endoplasmic reticulum alpha-mannosidase I. J Org Chem. 2005; 70(24):9892-904. DOI: 10.1021/jo0516382. View

11.

Gomes Ferreira I, Pucci M, Venturi G, Malagolini N, Chiricolo M, DallOlio F . Glycosylation as a Main Regulator of Growth and Death Factor Receptors Signaling. Int J Mol Sci. 2018; 19(2). PMC: 5855802. DOI: 10.3390/ijms19020580. View

12.

Vigerust D . Protein glycosylation in infectious disease pathobiology and treatment. Cent Eur J Biol. 2020; 6(5):802. PMC: 7088636. DOI: 10.2478/s11535-011-0050-8. View

13.

Marth J, Grewal P . Mammalian glycosylation in immunity. Nat Rev Immunol. 2008; 8(11):874-87. PMC: 2768770. DOI: 10.1038/nri2417. View

14.

Moothoo D, Canan B, Field R, Naismith J . Man alpha1-2 Man alpha-OMe-concanavalin A complex reveals a balance of forces involved in carbohydrate recognition. Glycobiology. 1999; 9(6):539-45. DOI: 10.1093/glycob/9.6.539. View

15.

Dawood A, Altobje M . Inhibition of N-linked Glycosylation by Tunicamycin May Contribute to The Treatment of SARS-CoV-2. Microb Pathog. 2020; 149:104586. PMC: 7573633. DOI: 10.1016/j.micpath.2020.104586. View

16.

Fouquaert E, Smith D, Peumans W, Proost P, Balzarini J, Savvides S . Related lectins from snowdrop and maize differ in their carbohydrate-binding specificity. Biochem Biophys Res Commun. 2009; 380(2):260-5. PMC: 2681488. DOI: 10.1016/j.bbrc.2009.01.048. View

17.

Mao H, Hart S, Schink A, Pollok B . Sortase-mediated protein ligation: a new method for protein engineering. J Am Chem Soc. 2004; 126(9):2670-1. DOI: 10.1021/ja039915e. View

18.

Hirakawa H, Ishikawa S, Nagamune T . Ca2+ -independent sortase-A exhibits high selective protein ligation activity in the cytoplasm of Escherichia coli. Biotechnol J. 2015; 10(9):1487-92. DOI: 10.1002/biot.201500012. View

19.

Diekman A, Norton E, Klotz K, Westbrook V, Herr J . Evidence for a unique N-linked glycan associated with human infertility on sperm CD52: a candidate contraceptive vaccinogen. Immunol Rev. 1999; 171:203-11. DOI: 10.1111/j.1600-065x.1999.tb01350.x. View

20.

Kaku H, Van Damme E, Peumans W, Goldstein I . Carbohydrate-binding specificity of the daffodil (Narcissus pseudonarcissus) and amaryllis (Hippeastrum hybr.) bulb lectins. Arch Biochem Biophys. 1990; 279(2):298-304. DOI: 10.1016/0003-9861(90)90495-k. View