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313 results on '"Pashkuleva, Iva"'

15. Cooling rate uncovers epimer-dependent supramolecular organization of carbohydrate amphiphiles.

Author

Castro, VÃnia I. B., Gao, Yuting, Brito, Alexandra, Chen, Jie, Reis, Rui L., Pashkuleva, Iva, and Pires, Ricardo A.

Abstract

We show distinct CH–π interactions and assembly pathways for the amphiphile N-(fluorenylmethoxycarbonyl)-galactosamine and its epimer N-(fluorenylmethoxycarbonyl)-glucosamine. These differences result in the formation of supramolecular nanofibrous systems with opposite chirality. Our results showcase the importance of the carbohydrates structural diversity for their specific biointeractions and the opportunity that their ample interactome offers for synthesis of versatile and tunable supramolecular (bio) materials. [ABSTRACT FROM AUTHOR]

Published
2024
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36. Hyaluronan Brush-like Copolymers Promote CD44 Declustering in Breast Cancer Cells

Author

Fundação para a Ciência e a Tecnologia (Portugal), Carvalho, Ana Maria, Valcárcel Barros, Jesús, Soares da Costa, Diana, Gomes, Marisa, Vázquez, José Antonio, Reis, Rui L., Novoa-Carballal, Ramón, Pashkuleva, Iva, Fundação para a Ciência e a Tecnologia (Portugal), Carvalho, Ana Maria, Valcárcel Barros, Jesús, Soares da Costa, Diana, Gomes, Marisa, Vázquez, José Antonio, Reis, Rui L., Novoa-Carballal, Ramón, and Pashkuleva, Iva

Abstract

We report on the synthesis of hyaluronan (HA) brush-like copolymers and their application as antagonists of tumorigenic CD44-HA interactions. HA (4.8 kDa, ca. 24 saccharides) was grafted on 2-hydrohyethyl methacrylate (HEMA) by end-on oxime ligation. The obtained copolymers were compared with low and high molecular weight HA in terms of hydrolysis kinetics in the presence of hyaluronidase (isothermal titration calorimetry) and interactions with CD44 (surface plasmon resonance). The results evidenced that the high molecular weight HA and HA-g-HEMA have a much higher affinity to CD44 than low molecular weight HA. Additionally, slower enzymatic degradation was observed for the copolymer, making it an excellent candidate for active targeting of tumorigenic CD44-HA interactions. We, therefore, investigated the effect of the copolymer on cancer cell lines with different expression of CD44 and observed an efficient declustering of CD44 that is usually associated with reduction of metastasis and drug resistance

Published
2022

42. List of Contributors

Author

Alemán, María Elena, Ambrosio, Luigi, Annabi, Nasim, Araújo, N.A.M., Azevedo, Helena S., Baidya, Avijit, Bandyopadhyay, Ashutosh, Barros, Alexandre, Bebiano, Luís B., Bhardwaj, Nandana, Bhatia, Dhiraj, Bider, Faina, Boccaccini, Aldo R., Boccafoschi, Francesca, Cagney, Lorna, Carballo-Pedrares, Natalia, Carton, Flavia, Carvalho, Mariana R., Cengiz, Ibrahim Fatih, Choi, Joo Hee, Cirulli, Angela, Colaço, R., Collins, Maurice N., Correia, Susana, Costa, João B., Costa, Rui R., Cucchiarini, Magali, Decante, Guy, Demitri, Christian, Deng, Xudong, Di Francesco, Dalila, Dias, C.S., Domingues, Beatriz, Donate, Ricardo, Du, Cong, Fresu, Luigia Grazia, Gangrade, Ankit, García-Díaz, María, Giussi, Juan, Golubczyk, Dominika, Gonçalves, Cristiana, Granja, Pedro L., Gupta, Sharad, Hivare, Pravin, Jangdey, Rajendra, Kalkowski, Lukasz, Khang, Gilson, Kharaziha, Mahshid, Kim, Changheon, Kim, Se Eun, Kim, Sooin, Kim, Sujin, Kim, Wooyoup, Kinsella, Joseph M., Kort-Mascort, Jacqueline, Kwiatkowska, Joanna, Lee, Kangwon, Lima, Estêvão, Lopes, Soraia V., Lourenço, Bianca N., Lyu, Yaqi, Madry, Henning, Maia, F. Raquel, Malysz-Cymborska, Izabela, Mandal, Biman B., Martínez, Elena, Monzón, Mario D., Moya, Sergio E., Munguia-Lopez, Jose G., Nakamura, Jin, Neves Borgheti-Cardoso, Livia, Nitti, Paola, Ohtsuki, Chikara, Oliveira, J. Miguel, Pacheco, Margarida, Parmar, Vijaykumar, Pashkuleva, Iva, Patel, Gayatri, Patel, Riya, Patel, Swayamprakash, Pereira, Rúben F., Pillai, Sangeeth, Pina, Sandra, Radhouani, Hajer, Regato, Maria, Reis, Rui L., Rey-Rico, Ana, Ribeiro, Viviana P., Sannino, Alessandro, Seo, Jinsol, Serro, A.P., Silva-Correia, Joana, Singh, Deependra, Singh, Manju Rawat, Singh, Yogendra Pratap, Solanki, Nehaba, Song, Jeong Eun, Sugawara-Narutaki, Ayae, Talmon, Maria, Thanusha, AV, Torras, Núria, Tran, Simon D., Tumursukh, Normin-Erdene, Venkatesan, Jagadeesh K., Walczak, Piotr, Wang, Xue-Ting, Wu, Zi Liang, Yin, Da-Chuan, Yuan, Yichen, Zhang, Tuo-Di, Zhang, Xi, Zhang, Yuli, Zheng, Si Yu, and Zhu, Zhiyue

Published
2024
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46. Minimalistic supramolecular proteoglycan mimics by co-assembly of aromatic peptide and carbohydrate amphiphiles† †Electronic supplementary information (ESI) available: Synthetic procedures and characterization data. See DOI: 10.1039/c8sc04361b

Author

Brito, Alexandra, Abul-Haija, Yousef M., da Costa, Diana Soares, Novoa-Carballal, Ramon, Reis, Rui L., Ulijn, Rein V., Pires, Ricardo A., and Pashkuleva, Iva

Subjects
Chemistry, technology, industry, and agriculture, macromolecular substances, complex mixtures
Abstract

A modular two-component supramolecular hydrogel composed of a peptide core and carbohydrate shell as a minimalistic mimic of proteoglycans., We report the co-assembly of aromatic carbohydrate and dipeptide amphiphiles under physiological conditions as a strategy to generate minimalistic proteoglycan mimics. The resulting nanofibers present a structural, fluorenylmethoxycarbonyl-diphenylalanine (Fmoc-FF) core and a functional carbohydrate (Fmoc-glucosamine-6-sulfate or -phosphate) shell. The size, degree of bundling and mechanical properties of the assembled structures depend on the chemical nature of the carbohydrate amphiphile used. In cell culture medium, these nanofibers can further organize into supramolecular hydrogels. We demonstrate that, similar to proteoglycans, the assembled gels prolong the stability of growth factors and preserve the viability of cultured cells. Our results demonstrate that this approach can be applied to the design of extracellular matrix (ECM) substitutes for future regenerative therapies.

Published
2018

47. Copolymers with hyalurinan branches as efficient antagonist of CD44 signalling in breast cancer cells

Author

Carvalho, Ana Maria, Novoa-Carballal, Ramón, Valcárcel Barros, Jesús, Gomes, Marisa, Vázquez, José Antonio, Reis, Rui L., Pashkuleva, Iva, Carvalho, Ana Maria, Novoa-Carballal, Ramón, Valcárcel Barros, Jesús, Gomes, Marisa, Vázquez, José Antonio, Reis, Rui L., and Pashkuleva, Iva

Abstract

CD44 is the main hyaluronan (HA) receptor involved in the communication of cells with their microenvironment. CD44/HA interactions and following signaling cascade(s) depend on HA size. In cancer, HA with high molecular weight interacts, organizes, and clusters several extracellular and membrane protei ns, including CD44, to form a dense and functional pericellular coat. [1] These interactions activate anti-apoptotic, pro-invasion, and migration signaling pathways, promote drug resistance, facilitate intravasation, protect against anoikis during circulation, and contribute to ectopic tissue colonization. [2] Inhibition of such CD44/HA interactions and CD44 clustering has been thus explored as a therapeutic target. [3] In this work, we synthesized poly(hydroxyethyl)methacrylate graft HA (HEMA-g-HA) by oxime reaction at the reducing end of HA (4.8 kDa). We studied the interactions of these copolymers with CD44 by Surface Plasmon Resonance (SPR) and compared them against HA of low (4.8 kDa) and high (1.35 MDa) molecular weight. All copolymers bind to CD44 with the high association and dissociation constants: we observed a much higher affinity of CD44 to HEMA-g-HA than to HA (4.8 kDa) and similar to the measured for HA (1.35 MDa). On the other hand, the degradation of HEMA-g-HA by hyaluronidase is slower than free HA as shown by isothermal titration calorimetry (ITC). These results indicated that HEMA-g-HA could be a good antagonist of CD44/HA signaling in cancers. To check this hypothesis, we studied the binding of HEMA-g-HA-Rho to GFP-CD44 in transfected Sk-Br-3 cells by Forster resonance energy transfer (FRET) microscopy. FRET showed no significant difference between the copolymer, HA of 4.8 kDa, and 1.35 MDa HA, suggesting the same binding sites. Competitive binding assays demonstrated similar activity for HEMA-g-HA and HA of 4.8 kDa, but Western blot and immunocytochemistry analysis evidenced that the copolymer regulates CD44 expression and location, promoting recep

Published
2021

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