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Caraballo, Remi
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Publikasjoner (10 av 17) Visa alla publikasjoner
Johansson, E., Caraballo, R., Zocher, G., Mistry, N., Arnberg, N., Stehle, T. & Elofsson, M. (2022). Exploring divalent conjugates of 5-N-acetyl-neuraminic acid as inhibitors of coxsackievirus A24 variant (CVA24v) transduction. RSC Advances, 12(4), 2319-2331
Åpne denne publikasjonen i ny fane eller vindu >>Exploring divalent conjugates of 5-N-acetyl-neuraminic acid as inhibitors of coxsackievirus A24 variant (CVA24v) transduction
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2022 (engelsk)Inngår i: RSC Advances, E-ISSN 2046-2069, Vol. 12, nr 4, s. 2319-2331Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Coxsackievirus A24 variant (CVA24v) is responsible for several outbreaks and two pandemics of the highly contagious eye infection acute hemorrhagic conjunctivitis (AHC). Currently, neither prevention (vaccines) nor treatments (antivirals) are available for combating this disease. CVA24v attaches to cells by binding Neu5Ac-containing glycans on the surface of cells which facilitates entry. Previously, we have demonstrated that pentavalent Neu5Ac conjugates attenuate CVA24v infection of human corneal epithelial (HCE) cells. In this study, we report on the structure-based design of three classes of divalent Neu5Ac conjugates, with varying spacer lengths, and their effect on CVA24v transduction in HCE cells. In relative terms, the most efficient class of divalent Neu5Ac conjugates are more efficient than the pentavalent Neu5Ac conjugates previously reported.

sted, utgiver, år, opplag, sider
Royal Society of Chemistry, 2022
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-192370 (URN)10.1039/d1ra08968d (DOI)000742407000001 ()2-s2.0-85123934421 (Scopus ID)
Forskningsfinansiär
Knut and Alice Wallenberg Foundation, 2013.0019
Tilgjengelig fra: 2022-02-11 Laget: 2022-02-11 Sist oppdatert: 2022-09-15bibliografisk kontrollert
Beyer, S., Kimani, M., Zhang, Y., Verhassel, A., Sternbæk, L., Wang, T., . . . Stollenwerk, M. M. (2022). Fluorescent Molecularly Imprinted Polymer Layers against Sialic Acid on Silica-Coated Polystyrene Cores — Assessment of the Binding Behavior to Cancer Cells. Cancers, 14(8), Article ID 1875.
Åpne denne publikasjonen i ny fane eller vindu >>Fluorescent Molecularly Imprinted Polymer Layers against Sialic Acid on Silica-Coated Polystyrene Cores — Assessment of the Binding Behavior to Cancer Cells
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2022 (engelsk)Inngår i: Cancers, ISSN 2072-6694, Vol. 14, nr 8, artikkel-id 1875Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Sialic acid (SA) is a monosaccharide usually linked to the terminus of glycan chains on the cell surface. It plays a crucial role in many biological processes, and hypersialylation is a common feature in cancer. Lectins are widely used to analyze the cell surface expression of SA. However, these protein molecules are usually expensive and easily denatured, which calls for the development of alternative glycan-specific receptors and cell imaging technologies. In this study, SA-imprinted fluorescent core-shell molecularly imprinted polymer particles (SA-MIPs) were employed to recognize SA on the cell surface of cancer cell lines. The SA-MIPs improved suspensibility and scattering properties compared with previously used core-shell SA-MIPs. Although SA-imprinting was performed using SA without preference for the α2,3-and α2,6-SA forms, we screened the cancer cell lines analyzed using the lectins Maackia Amurensis Lectin I (MAL I, α2,3-SA) and Sambucus Nigra Lectin (SNA, α2,6-SA). Our results show that the selected cancer cell lines in this study presented a varied binding behavior with the SA-MIPs. The binding pattern of the lectins was also demonstrated. Moreover, two different pentavalent SA conjugates were used to inhibit the binding of the SA-MIPs to breast, skin, and lung cancer cell lines, demonstrating the specificity of the SA-MIPs in both flow cytometry and confocal fluorescence microscopy. We concluded that the synthesized SA-MIPs might be a powerful future tool in the diagnostic analysis of various cancer cells.

sted, utgiver, år, opplag, sider
MDPI, 2022
Emneord
cancer, imprinting, molecularly imprinted polymers, SA conjugates, sialic acid
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-194273 (URN)10.3390/cancers14081875 (DOI)000786858400001 ()2-s2.0-85127781436 (Scopus ID)
Tilgjengelig fra: 2022-04-29 Laget: 2022-04-29 Sist oppdatert: 2023-09-05bibliografisk kontrollert
Johansson, E., Caraballo, R., Hurdiss, D. L., Mistry, N., Andersson, C. D., Thompson, R. F., . . . Elofsson, M. (2021). Exploring the effect of structure-based scaffold hopping on the inhibition of coxsackievirus a24v transduction by pentavalent n-acetylneuraminic acid conjugates. International Journal of Molecular Sciences, 22(16), Article ID 8418.
Åpne denne publikasjonen i ny fane eller vindu >>Exploring the effect of structure-based scaffold hopping on the inhibition of coxsackievirus a24v transduction by pentavalent n-acetylneuraminic acid conjugates
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2021 (engelsk)Inngår i: International Journal of Molecular Sciences, ISSN 1661-6596, E-ISSN 1422-0067, Vol. 22, nr 16, artikkel-id 8418Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Coxsackievirus A24 variant (CVA24v) is the primary causative agent of the highly contagious eye infection designated acute hemorrhagic conjunctivitis (AHC). It is solely responsible for two pandemics and several recurring outbreaks of the disease over the last decades, thus affecting millions of individuals throughout the world. To date, no antiviral agents or vaccines are available for combating this disease, and treatment is mainly supportive. CVA24v utilizes Neu5Ac-containing glycans as attachment receptors facilitating entry into host cells. We have previously reported that pentavalent Neu5Ac conjugates based on a glucose-scaffold inhibit CVA24v infection of human corneal epithelial cells. In this study, we report on the design and synthesis of scaffold-replaced pentavalent Neu5Ac conjugates and their effect on CVA24v cell transduction and the use of cryogenic electron microscopy (cryo-EM) to study the binding of these multivalent conjugates to CVA24v. The results presented here provide insights into the development of Neu5Ac-based inhibitors of CVA24v and, most significantly, the first application of cryo-EM to study the binding of a multivalent ligand to a lectin.

sted, utgiver, år, opplag, sider
MDPI, 2021
Emneord
5-N-acetylneuraminic acid, Antivirals, Conjunctivitis, Coxsackievirus A24v, Cryo-EM, Multivalency, Sialic acid conjugates
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-186555 (URN)10.3390/ijms22168418 (DOI)000689130700001 ()2-s2.0-85111762142 (Scopus ID)
Tilgjengelig fra: 2021-08-11 Laget: 2021-08-11 Sist oppdatert: 2023-09-05bibliografisk kontrollert
El-Schich, Z., Zhang, Y., Göransson, T., Dizeyi, N., Persson, J. L., Johansson, E., . . . Wingren, A. G. (2021). Sialic acid as a biomarker studied in breast cancer cell lines in vitro using fluorescent molecularly imprinted polymers. Applied Sciences, 11(7), Article ID 3256.
Åpne denne publikasjonen i ny fane eller vindu >>Sialic acid as a biomarker studied in breast cancer cell lines in vitro using fluorescent molecularly imprinted polymers
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2021 (engelsk)Inngår i: Applied Sciences, E-ISSN 2076-3417, Vol. 11, nr 7, artikkel-id 3256Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Sialylations are post-translational modifications of proteins and lipids that play important roles in many cellular events, including cell-cell interactions, proliferation, and migration. Tumor cells express high levels of sialic acid (SA), which are often associated with the increased invasive potential in clinical tumors, correlating with poor prognosis. To overcome the lack of natural SA-receptors, such as antibodies and lectins with high enough specificity and sensitivity, we have used molecularly imprinted polymers (MIPs), or “plastic antibodies”, as nanoprobes. Because high expression of epithelial cell adhesion molecule (EpCAM) in primary tumors is often associated with proliferation and a more aggressive phenotype, the expression of EpCAM and CD44 was initially analyzed. The SA-MIPs were used for the detection of SA on the cell surface of breast cancer cells. Lectins that specifically bind to the a-2,3 SA and a-2,6 SA variants were used for analysis of SA expression, with both flow cytometry and confocal microscopy. Here we show a correlation of EpCAM and SA expression when using the SA-MIPs for detection of SA. We also demonstrate the binding pattern of the SA-MIPs on the breast cancer cell lines using confocal microscopy. Pre-incubation of the SA-MIPs with SA-derivatives as inhibitors could reduce the binding of the SA-MIPs to the tumor cells, indicating the specificity of the SA-MIPs. In conclusion, the SA-MIPs may be a new powerful tool in the diagnostic analysis of breast cancer cells.

sted, utgiver, år, opplag, sider
MDPI, 2021
Emneord
Breast cancer, Epithelial cell adhesion molecule, Molecularly imprinted polymers, Nanoparticles, Sialic acid
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-182753 (URN)10.3390/app11073256 (DOI)000638354600001 ()2-s2.0-85104259855 (Scopus ID)
Tilgjengelig fra: 2021-05-24 Laget: 2021-05-24 Sist oppdatert: 2023-09-05bibliografisk kontrollert
Johansson, E., Caraballo, R. & Elofsson, M. (2021). Synthesis of 4-O-alkylated N-acetylneuraminic acid derivatives. Journal of Organic Chemistry, 86(13), 9145-9154
Åpne denne publikasjonen i ny fane eller vindu >>Synthesis of 4-O-alkylated N-acetylneuraminic acid derivatives
2021 (engelsk)Inngår i: Journal of Organic Chemistry, ISSN 0022-3263, E-ISSN 1520-6904, Vol. 86, nr 13, s. 9145-9154Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The synthesis of 4-O-alkyl analogs of N-acetylneuraminic acid (Neu5Ac) and the scope of the reaction are described. Activated alkyl halides and sulfonates and primary alkyl iodides give products in useful yields. The utility of the methodology is exemplified using a thiophenyl Neu5Ac building block to synthesize a 4-O-alkyl DANA analog. These results expand the toolbox of Neu5Ac chemistry with value in drug discovery and for the design of novel tools to study the biology of Neu5Ac lectins. 

sted, utgiver, år, opplag, sider
American Chemical Society (ACS), 2021
HSV kategori
Forskningsprogram
organisk kemi
Identifikatorer
urn:nbn:se:umu:diva-182319 (URN)10.1021/acs.joc.1c00235 (DOI)000670661000052 ()34138565 (PubMedID)2-s2.0-85110169034 (Scopus ID)
Forskningsfinansiär
Knut and Alice Wallenberg Foundation, 2013.0019
Tilgjengelig fra: 2021-04-19 Laget: 2021-04-19 Sist oppdatert: 2024-01-03bibliografisk kontrollert
Johansson, E., Caraballo, R., Mistry, N., Zocher, G., Qian, W., Andersson, C. D., . . . Elofsson, M. (2020). Pentavalent Sialic Acid Conjugates Block Coxsackievirus A24 Variant and Human Adenovirus Type 37-Viruses That Cause Highly Contagious Eye Infections. ACS Chemical Biology, 15(10), 2683-2691
Åpne denne publikasjonen i ny fane eller vindu >>Pentavalent Sialic Acid Conjugates Block Coxsackievirus A24 Variant and Human Adenovirus Type 37-Viruses That Cause Highly Contagious Eye Infections
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2020 (engelsk)Inngår i: ACS Chemical Biology, ISSN 1554-8929, E-ISSN 1554-8937, Vol. 15, nr 10, s. 2683-2691Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Coxsackievirus A24 variant (CVA24v) and human adenovirus 37 (HAdV-37) are leading causative agents of the severe and highly contagious ocular infections acute hemorrhagic conjunctivitis and epidemic keratoconjunctivitis, respectively. Currently, neither vaccines nor antiviral agents are available for treating these diseases, which affect millions of individuals worldwide. CVA24v and HAdV-37 utilize sialic acid as attachment receptors facilitating entry into host cells. Previously, we and others have shown that derivatives based on sialic acid are effective in preventing HAdV-37 binding and infection of cells. Here, we designed and synthesized novel pentavalent sialic acid conjugates and studied their inhibitory effect against CVA24v and HAdV-37 binding and infection of human corneal epithelial cells. The pentavalent conjugates are the first reported inhibitors of CVA24v infection and proved efficient in blocking HAdV-37 binding. Taken together, the pentavalent conjugates presented here form a basis for the development of general inhibitors of these highly contagious ocular pathogens.

sted, utgiver, år, opplag, sider
American Chemical Society (ACS), 2020
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-176796 (URN)10.1021/acschembio.0c00446 (DOI)000582580100008 ()32845119 (PubMedID)2-s2.0-85093538705 (Scopus ID)
Tilgjengelig fra: 2020-11-24 Laget: 2020-11-24 Sist oppdatert: 2023-03-24bibliografisk kontrollert
Chandra, N., Frängsmyr, L., Imhof, S., Caraballo, R., Elofsson, M. & Arnberg, N. (2019). Sialic Acid-Containing Glycans as Cellular Receptors for Ocular Human Adenoviruses: Implications for Tropism and Treatment. Viruses, 11(5), Article ID 395.
Åpne denne publikasjonen i ny fane eller vindu >>Sialic Acid-Containing Glycans as Cellular Receptors for Ocular Human Adenoviruses: Implications for Tropism and Treatment
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2019 (engelsk)Inngår i: Viruses, E-ISSN 1999-4915, Vol. 11, nr 5, artikkel-id 395Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Human adenoviruses (HAdV) are the most common cause of ocular infections. Species B human adenovirus type 3 (HAdV-B3) causes pharyngoconjunctival fever (PCF), whereas HAdV-D8, -D37, and -D64 cause epidemic keratoconjunctivitis (EKC). Recently, HAdV-D53, -D54, and -D56 emerged as new EKC-causing agents. HAdV-E4 is associated with both PCF and EKC. We have previously demonstrated that HAdV-D37 uses sialic acid (SA)-containing glycans as cellular receptors on human corneal epithelial (HCE) cells, and the virus interaction with SA is mediated by the knob domain of the viral fiber protein. Here, by means of cell-based assays and using neuraminidase (a SA-cleaving enzyme), we investigated whether ocular HAdVs other than HAdV-D37 also use SA-containing glycans as receptors on HCE cells. We found that HAdV-E4 and -D56 infect HCE cells independent of SAs, whereas HAdV-D53 and -D64 use SAs as cellular receptors. HAdV-D8 and -D54 fiber knobs also bound to cell-surface SAs. Surprisingly, HCE cells were found resistant to HAdV-B3 infection. We also demonstrated that the SA-based molecule i.e., ME0462, designed to bind to SA-binding sites on the HAdV-D37 fiber knob, efficiently prevents binding and infection of several EKC-causing HAdVs. Surface plasmon resonance analysis confirmed a direct interaction between ME0462 and fiber knobs. Altogether, we demonstrate that SA-containing glycans serve as receptors for multiple EKC-causing HAdVs, and, that SA-based compound function as a broad-spectrum antiviral against known and emerging EKC-causing HAdVs.

sted, utgiver, år, opplag, sider
MDPI, 2019
Emneord
adenovirus, cellular receptor, epidemic keratoconjunctivitis, pharyngoconjunctival fever, sialic acid, tropism
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-159268 (URN)10.3390/v11050395 (DOI)000472676600006 ()31035532 (PubMedID)2-s2.0-85065483937 (Scopus ID)
Forskningsfinansiär
Knut and Alice Wallenberg Foundation, 2013.0019
Tilgjengelig fra: 2019-05-23 Laget: 2019-05-23 Sist oppdatert: 2024-01-17bibliografisk kontrollert
Karlberg, T., Hornyak, P., Pinto, A. F., Milanova, S., Ebrahimi, M., Lindberg, M. J., . . . Schüler, H. (2018). 14-3-3 proteins activate Pseudomonas exotoxins-S and -T by chaperoning a hydrophobic surface. Nature Communications, 9, Article ID 3785.
Åpne denne publikasjonen i ny fane eller vindu >>14-3-3 proteins activate Pseudomonas exotoxins-S and -T by chaperoning a hydrophobic surface
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2018 (engelsk)Inngår i: Nature Communications, E-ISSN 2041-1723, Vol. 9, artikkel-id 3785Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Pseudomonas are a common cause of hospital-acquired infections that may be lethal. ADP-ribosyltransferase activities of Pseudomonas exotoxin-S and -T depend on 14-3-3 proteins inside the host cell. By binding in the 14-3-3 phosphopeptide binding groove, an amphipathic C-terminal helix of ExoS and ExoT has been thought to be crucial for their activation. However, crystal structures of the 14-3-3 beta: ExoS and -ExoT complexes presented here reveal an extensive hydrophobic interface that is sufficient for complex formation and toxin activation. We show that C-terminally truncated ExoS ADP-ribosyltransferase domain lacking the amphipathic binding motif is active when co-expressed with 14-3-3. Moreover, swapping the amphipathic C-terminus with a fragment from Vibrio Vis toxin creates a 14-3-3 independent toxin that ADP-ribosylates known ExoS targets. Finally, we show that 14-3-3 stabilizes ExoS against thermal aggregation. Together, this indicates that 14-3-3 proteins activate exotoxin ADP-ribosyltransferase domains by chaperoning their hydrophobic surfaces independently of the amphipathic C-terminal segment.

sted, utgiver, år, opplag, sider
Nature Publishing Group, 2018
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-152249 (URN)10.1038/s41467-018-06194-1 (DOI)000444757900003 ()30224724 (PubMedID)2-s2.0-85053414923 (Scopus ID)
Forskningsfinansiär
Swedish Foundation for Strategic Research , SB12-0022Swedish Research Council, 2012-2802Swedish Research Council, 2015-4200Swedish Research Council, 2015-4603Wenner-Gren Foundations
Tilgjengelig fra: 2018-10-04 Laget: 2018-10-04 Sist oppdatert: 2023-03-28bibliografisk kontrollert
Zetterström, C. E., Uusitalo, P., Qian, W., Hinch, S., Caraballo, R., Grundström, C. & Elofsson, M. (2018). Screening for Inhibitors of Acetaldehyde Dehydrogenase (AdhE) from Enterohemorrhagic Escherichia coli (EHEC). SLAS Discovery, 23(8), 815-822
Åpne denne publikasjonen i ny fane eller vindu >>Screening for Inhibitors of Acetaldehyde Dehydrogenase (AdhE) from Enterohemorrhagic Escherichia coli (EHEC)
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2018 (engelsk)Inngår i: SLAS Discovery, ISSN 2472-5552, Vol. 23, nr 8, s. 815-822Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

Acetaldehyde dehydrogenase (AdhE) is a bifunctional acetaldehyde-coenzyme A (CoA) dehydrogenase and alcohol dehydrogenase involved in anaerobic metabolism in gram-negative bacteria. This enzyme was recently found to be a key regulator of the type three secretion (T3S) system in Escherichia coli. AdhE inhibitors can be used as tools to study bacterial virulence and a starting point for discovery of novel antibacterial agents. We developed a robust enzymatic assay, based on the acetaldehyde-CoA dehydrogenase activity of AdhE using both absorption and fluorescence detection models (Z' > 0.7). This assay was used to screen similar to 11,000 small molecules in 384-well format that resulted in three hits that were confirmed by resynthesis and validation. All three compounds are noncompetitive with respect to acetaldehyde and display a clear dose-response effect with hill slopes of 1-2. These new inhibitors will be used as chemical tools to study the interplay between metabolism and virulence and the role of AdhE in T3S regulation in gram-negative bacteria, and as starting points for the development of novel antibacterial agents.

sted, utgiver, år, opplag, sider
Sage Publications, 2018
Emneord
EHEC, AdhE, screening, absorbance, fluorescence
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-151545 (URN)10.1177/2472555218768062 (DOI)000442275300005 ()29630847 (PubMedID)2-s2.0-85045153105 (Scopus ID)
Forskningsfinansiär
Swedish Research Council
Tilgjengelig fra: 2018-09-11 Laget: 2018-09-11 Sist oppdatert: 2023-03-24bibliografisk kontrollert
Caraballo, R., Larsson, M., Nilsson, S. K., Ericsson, M., Qian, W., Tran, N. P., . . . Elofsson, M. (2015). Structure-activity relationships for lipoprotein lipase agonists that lower plasma triglycerides in vivo. European Journal of Medicinal Chemistry, 103, 191-209
Åpne denne publikasjonen i ny fane eller vindu >>Structure-activity relationships for lipoprotein lipase agonists that lower plasma triglycerides in vivo
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2015 (engelsk)Inngår i: European Journal of Medicinal Chemistry, ISSN 0223-5234, E-ISSN 1768-3254, Vol. 103, s. 191-209Artikkel i tidsskrift (Fagfellevurdert) Published
Abstract [en]

The risk of cardiovascular events increases in individuals with elevated plasma triglyceride (TG) levels, therefore advocating the need for efficient TG-lowering drugs. In the blood circulation, TG levels are regulated by lipoprotein lipase (LPL), an unstable enzyme that is only active as a non-covalently associated homodimer. We recently reported on a N-phenylphthalimide derivative (1) that stabilizes LPL in vitro, and moderately lowers triglycerides in vivo (Biochem. Biophys. Res. Common. 2014, 450, 1063). Herein, we establish structure activity relationships of 51 N-phenylphthalimide analogs of the screening hit 1. In vitro evaluation highlighted that modifications on the phthalimide moiety were not tolerated and that lipophilic substituents on the central phenyl ring were functionally essential. The substitution pattern on the central phenyl ring also proved important to stabilize LPL However, in vitro testing demonstrated rapid degradation of the phthalimide fragment in plasma which was addressed by replacing the phthalimide scaffold with other heterocyclic fragments. The in vitro potency was retained or improved and substance 80 proved stable in plasma and efficiently lowered plasma TGs in vivo. 2015 The Authors. Published by Elsevier Masson SAS.

sted, utgiver, år, opplag, sider
Elsevier, 2015
Emneord
Lipoprotein lipase, LPL, Triglyceride, Structure-activity relationship, Agonist
HSV kategori
Identifikatorer
urn:nbn:se:umu:diva-111481 (URN)10.1016/j.ejmech.2015.08.058 (DOI)000363344700015 ()26355531 (PubMedID)2-s2.0-84941116388 (Scopus ID)
Tilgjengelig fra: 2015-12-08 Laget: 2015-11-13 Sist oppdatert: 2023-03-24bibliografisk kontrollert
Organisasjoner