Dancing with Nucleobases: Unveiling the Self-Assembly Properties of DNA and RNA Base-Containing Molecules for Gel Formation(89 views) Scognamiglio PL, Vicidomini C, Roviello GN
Pasqualina Liana Scognamiglio 1,†, Caterina Vicidomini 2,† and Giovanni N. Roviello 2,*1 Department of Sciences, University of Basilicata, Via dell’Ateneo Lucano 10, 85100 Potenza, Italy; pasqualina.scognamiglio@unibas.it2 Institute of Biostructures and Bioimaging, Italian National Council for Research (IBB-CNR), Area di Ricerca Site and Headquarters, Via Pietro Castellino 111, 80131 Naples, Italy; cateri-na.vicidomini@ibb.cnr.it* Correspondence: giovanni.roviello@cnr.it; Tel.: +39-0812203415† These authors contributed equally to this work.
2. Rogovina, L.Z.; Vasil’ev, V.G.; Braudo, E. Definition of the concept of polymer gel. Polym. Sci. Ser. C 2008, 50, 85–92.
3. Yamauchi, A. Gels: Introduction. In Gels Handbook; Elsevier: Amsterdam, The Netherlands, 2001; pp. 4–12.
4. Draper, E.R.; Adams, D.J. Low-molecular-weight gels: The state of the art. Chem 2017, 3, 390–410.
5. Banerjee, S.; Bhattacharya, S. Food gels: Gelling process and new applications. Crit. Rev. Food Sci. Nutr. 2012, 52, 334–346.
6. Siddiqui, S.A.; Alvi, T.; Biswas, A.; Shityakov, S.; Gusinskaia, T.; Lavrentev, F.; Dutta, K.; Khan, M.K.I.; Stephen, J.; Radhakrishnan, M. Food gels: Principles, interaction mechanisms and its microstructure. Crit. Rev. Food Sci. Nutr. 2022, 2, 1–22.
7. Nazir, A.; Asghar, A.; Maan, A.A. Food gels: Gelling process and new applications. In Advances in Food Rheology and Its Applications; Elsevier: Amsterdam, The Netherlands, 2017; pp. 335–353.
8. Nayak, A.K.; Das, B. Introduction to polymeric gels. In Polymeric Gels; Elsevier: Amsterdam, The Netherlands, 2018; pp. 3–27.
9. Vashist, A.; Vashist, A.; Gupta, Y.; Ahmad, S. Recent advances in hydrogel based drug delivery systems for the human body. J. Mater. Chem. B 2014, 2, 147–166.
10. Chamkouri, H.; Chamkouri, M. A review of hydrogels, their properties and applications in medicine. Am. J. Biomed. Sci. Res. 2021, 11, 485–493.
11. Hwang, H.S.; Lee, C.-S. Recent progress in hyaluronic-acid-based hydrogels for bone tissue engineering. Gels 2023, 9, 588.
12. Kopeček, J. Hydrogel biomaterials: A smart future? Biomaterials 2007, 28, 5185–5192.
13. Shakeel, S.; Karim, S.; Ali, A. Peptide nucleic acid (PNA)—A review. J. Chem. Technol. Biotechnol. Int. Res. Process Environ. Clean Technol. 2006, 81, 892–899.
14. Rodrigues, T.; Curti, F.; Leroux, Y.R.; Barras, A.; Pagneux, Q.; Happy, H.; Kleber, C.; Boukherroub, R.; Hasler, R.; Volpi, S. Discovery of a Peptide Nucleic Acid (PNA) aptamer for cardiac troponin I: Substituting DNA with neutral PNA maintains picomolar affinity and improves performances for electronic sensing with graphene field-effect transistors (gFET). Nano Today 2023, 50, 101840.
15. Pradeep, S.P.; Malik, S.; Slack, F.J.; Bahal, R. Unlocking the potential of chemically modified peptide nucleic acids for RNA-based therapeutics. RNA 2023, 29, 434–445.
16. Chu, T.-W.; Feng, J.; Yang, J.; Kopeček, J. Hybrid polymeric hydrogels via peptide nucleic acid (PNA)/DNA complexation. J. Control. Release 2015, 220, 608–616.
17. Park, S.J.; Park, S.M.; Kim, W.-k.; Lee, J. Hydrogel-based thermosensor using peptide nucleic acid and PEGylated graphene oxide. Anal. Chim. Acta 2023, 1239, 340708.
19. Agrawal, N.K.; Allen, P.; Song, Y.H.; Wachs, R.A.; Du, Y.; Ellington, A.D.; Schmidt, C.E. Oligonucleotide-functionalized hydrogels for sustained release of small molecule (aptamer) therapeutics. Acta Biomater. 2020, 102, 315–325.
20. Liu, J. Oligonucleotide-functionalized hydrogels as stimuli responsive materials and biosensors. Soft Matter 2011, 7, 6757–6767.
21. Bhattacharyya, T.; Saha, P.; Dash, J. Guanosine-derived supramolecular hydrogels: Recent developments and future opportunities. ACS Omega 2018, 3, 2230–2241.
22. Ye, X.; Li, X.; Shen, Y.; Chang, G.; Yang, J.; Gu, Z. Self-healing pH-sensitive cytosine-and guanosine-modified hyaluronic acid hydrogels via hydrogen bonding. Polymer 2017, 108, 348–360.
23. Merino-Gómez, M.; Godoy-Gallardo, M.; Wendner, M.; Mateos-Timoneda, M.A.; Gil, F.J.; Perez, R.A. Optimization of guanosine-based hydrogels with boric acid derivatives for enhanced long-term stability and cell survival. Front. Bioeng. Biotechnol. 2023, 11, 1147943.
24. Godoy-Gallardo, M.; Merino-Gómez, M.; Mateos-Timoneda, M.A.; Eckhard, U.; Gil, F.J.; Perez, R.A. Advanced Binary Guanosine and Guanosine 5'-Monophosphate Cell-Laden Hydrogels for Soft Tissue Reconstruction by 3D Bioprinting. ACS Appl. Mater. Interfaces 2023. https://doi.org/10.1021/acsami.2c23277
25. Tripathi, M.; Sharma, R.; Hussain, A.; Kumar, I.; Sharma, A.K.; Sarkar, A. Hydrogels and their combination with lipids and nucleotides. In Sustainable Hydrogels; Elsevier: Amsterdam, The Netherlands, 2023; pp. 471–487.
26. Peters, G.M.; Davis, J.T. Supramolecular gels made from nucleobase, nucleoside and nucleotide analogs. Chem. Soc. Rev. 2016, 45, 3188–3206.
27. Godeau, G.; Brun, C.; Arnion, H.; Staedel, C.; Barthélémy, P. Glycosyl-nucleoside fluorinated amphiphiles as components of nanostructured hydrogels. Tetrahedron Lett. 2010, 51, 1012–1015.
28. Godoy-Gallardo, M.; Merino-Gómez, M.; Matiz, L.C.; Mateos-Timoneda, M.A.; Gil, F.J.; Perez, R.A. Nucleoside-based supramolecular hydrogels: From synthesis and structural properties to biomedical and tissue engineering applications. ACS Biomater. Sci. Eng. 2022, 9, 40–61.
29. Ignatowska, J.; Mironiuk-Puchalska, E.; Grześkowiak, P.; Wińska, P.; Wielechowska, M.; Bretner, M.; Karatsai, O.; Rędowicz, M.J.; Koszytkowska-Stawińska, M. New insight into nucleo α-amino acids–Synthesis and SAR studies on cytotoxic activity of β-pyrimidine alanines. Bioorg. Chem. 2020, 100, 103864.
30. More, J.C.; Troop, H.M.; Dolman, N.P.; Jane, D.E. Structural requirements for novel willardiine derivatives acting as AMPA and kainate receptor antagonists. Br. J. Pharmacol. 2003, 138, 1093–1100.
31. Mik, V.; Mičková, Z.; Doležal, K.; Frébort, I.; Pospisil, T. Activity of (+)-Discadenine as a plant cytokinin. J. Nat. Prod. 2017, 80, 2136–2140.
32. Xu, Q.; Song, B.; Liu, F.; Song, Y.; Chen, P.; Liu, S.; Krishnan, H.B. Identification and characterization of β-Lathyrin, an abundant glycoprotein of grass pea (Lathyrus sativus L.), as a potential allergen. J. Agric. Food Chem. 2018, 66, 8496–8503.
33. Roviello, G.N.; Gaetano, S.D.; Capasso, D.; Cesarani, A.; Bucci, E.M.; Pedone, C. Synthesis, spectroscopic studies and biological activity of a novel nucleopeptide with Moloney murine leukemia virus reverse transcriptase inhibitory activity. Amino Acids 2010, 38, 1489–1496.
34. Roviello, G.N.; Musumeci, D.; De Cristofaro, A.; Capasso, D.; Di Gaetano, S.; Bucci, E.M.; Pedone, C. Alternate dab-aeg PNAs: Synthesis, nucleic acid binding studies and biological activity. Mol. Biosyst. 2009, 6, 199–205.
35. Roviello, G.; Musumeci, D.; Castiglione, M.; Bucci, E.; Pedone, C.; Benedetti, E. Solid phase synthesis and RNA‐binding studies of a serum‐resistant nucleo‐ε‐peptide. J. Pept. Sci. Off. Publ. Eur. Pept. Soc. 2009, 15, 155–160.
36. Roviello, G.N.; Moccia, M.; Sapio, R.; Valente, M.; Bucci, E.; Castiglione, M.; Pedone, C.; Perretta, G.; Benedetti, E.; Musumeci, D. Synthesis, characterization and hybridization studies of new nucleo‐γ‐peptides based on diaminobutyric acid. J. Pept. Sci. Off. Publ. Eur. Pept. Soc. 2006, 12, 829–835.
37. Roviello, V.; Musumeci, D.; Mokhir, A.; Roviello, G.N. Evidence of protein binding by a nucleopeptide based on a thyminedecorated L-diaminopropanoic acid through CD and in silico studies. Curr. Med. Chem. 2021, 28, 5004–5015.
38. Hoschtettler, P.; Pickaert, G.; Carvalho, A.; Averlant-Petit, M.-C.; Stefan, L. Highly Synergistic Properties of Multicomponent Hydrogels Thanks to Cooperative Nucleopeptide Assemblies. Chem. Mater. 2023, 35, 4259–4275.
39. Musumeci, D.; Ullah, S.; Ikram, A.; Roviello, G.N. Novel insights on nucleopeptide binding: A spectroscopic and In Silico investigation on the interaction of a thymine-bearing tetrapeptide with a homoadenine DNA. J. Mol. Liq. 2022, 347, 117975.
40. Boback, K.; Bacchi, K.; O’Neill, S.; Brown, S.; Dorsainvil, J.; Smith-Carpenter, J.E. Impact of C-terminal chemistry on self-assembled morphology of guanosine containing nucleopeptides. Molecules 2020, 25, 5493.
41. Datta, A. Synthetic Studies on Antifungal Peptidyl Nucleoside Antibiotics. Chem. Synth. Nucleoside Analog. 2013, 819–846. https://doi.org/10.1002/9781118498088.ch18
42. Swinehart, W.; Deutsch, C.; Sarachan, K.L.; Luthra, A.; Bacusmo, J.M.; de Crécy-Lagard, V.; Swairjo, M.A.; Agris, P.F.; Iwata-Reuyl, D. Specificity in the biosynthesis of the universal tRNA nucleoside N6-threonylcarbamoyl adenosine (t6A)—TsaD is the gatekeeper. RNA 2020, 26, 1094–1103.
43. Roviello, G.N.; Benedetti, E.; Pedone, C.; Bucci, E.M. Nucleobase-containing peptides: An overview of their characteristic features and applications. Amino Acids 2010, 39, 45–57.
44. Kurbasic, M.; Garcia, A.M.; Viada, S.; Marchesan, S. Tripeptide self-assembly into bioactive hydrogels: Effects of terminus modification on biocatalysis. Molecules 2021, 26, 173.
45. Snip, E.; Koumoto, K.; Shinkai, S. Gel formation properties of a uracil-appended cholesterol gelator and cooperative effects of the complementary nucleobases. Tetrahedron 2002, 58, 8863–8873.
46. Marchesan, S.; Vargiu, A.V.; Styan, K.E. The Phe-Phe motif for peptide self-assembly in nanomedicine. Molecules 2015, 20, 19775–19788.
47. Dinesh, B.; Squillaci, M.A.; Ménard-Moyon, C.; Samorì, P.; Bianco, A. Self-assembly of diphenylalanine backbone homologues and their combination with functionalized carbon nanotubes. Nanoscale 2015, 7, 15873–15879.
48. Roviello, G.N. Novel insights into nucleoamino acids: Biomolecular recognition and aggregation studies of a thymine-conjugated l-phenyl alanine. Amino Acids 2018, 50, 933–941.
49. Scognamiglio, P.L.; Riccardi, C.; Palumbo, R.; Gale, T.F.; Musumeci, D.; Roviello, G.N. Self-assembly of thyminyl l-tryptophanamide (TrpT) building blocks for the potential development of drug delivery nanosystems. J. Nanostructure Chem. 2023, 1–19. https://doi.org/10.1007/s40097-023-00523-7
50. Guida, S.; Arginelli, F.; Farnetani, F.; Ciardo, S.; Bertoni, L.; Manfredini, M.; Zerbinati, N.; Longo, C.; Pellacani, G. Clinical applications of in vivo and ex vivo confocal microscopy. Appl. Sci. 2021, 11, 1979.
51. Li, X.; Kuang, Y.; Lin, H.-C.; Gao, Y.; Shi, J.; Xu, B. Supramolecular nanofibers and hydrogels of nucleopeptides. Angew. Chem. Int. Ed. Engl. 2011, 50, 9365.
52. Yuan, D.; Du, X.; Shi, J.; Zhou, N.; Zhou, J.; Xu, B. Mixing biomimetic heterodimers of nucleopeptides to generate biocompatible and biostable supramolecular hydrogels. Angew. Chem. 2015, 127, 5797–5800.
53. Ewert, E.; Pospieszna-Markiewicz, I.; Szymańska, M.; Kurkiewicz, A.; Belter, A.; Kubicki, M.; Patroniak, V.; Fik-Jaskółka, M.A.; Roviello, G.N. New N4-Donor Ligands as Supramolecular Guests for DNA and RNA: Synthesis, Structural Characterization, In Silico, Spectrophotometric and Antimicrobial Studies. Molecules 2023, 28, 400.
54. Baek, K.; Noblett, A.D.; Ren, P.; Suggs, L.J. Self-assembled nucleo-tripeptide hydrogels provide local and sustained doxorubicin release. Biomater. Sci. 2020, 8, 3130–3137.
55. Giraud, T.; Bouguet-Bonnet, S.; Marchal, P.; Pickaert, G.; Averlant-Petit, M.-C.; Stefan, L. Improving and fine-tuning the properties of peptide-based hydrogels via incorporation of peptide nucleic acids. Nanoscale 2020, 12, 19905–19917.
57. Du, X.; Zhou, J.; Li, X.; Xu, B. Self-assembly of nucleopeptides to interact with DNAs. Interface Focus 2017, 7, 20160116.
58. Roviello, G.N.; Musumeci, D.; Bucci, E.M.; Pedone, C. Evidences for supramolecular organization of nucleopeptides: Synthesis, spectroscopic and biological studies of a novel dithymine L-serine tetrapeptide. Mol. BioSyst. 2011, 7, 1073–1080.
59. Roviello, G.N.; Ricci, A.; Bucci, E.M.; Pedone, C. Synthesis, biological evaluation and supramolecular assembly of novel analogues of peptidyl nucleosides. Mol. BioSyst. 2011, 7, 1773–1778.
60. Giraud, T.; Hoschtettler, P.; Pickaert, G.; Averlant-Petit, M.-C.; Stefan, L. Emerging low-molecular weight nucleopeptide-based hydrogels: State of the art, applications, challenges and perspectives. Nanoscale 2022, 14, 4908–4921.
61. Scognamiglio, P.L.; Platella, C.; Napolitano, E.; Musumeci, D.; Roviello, G.N. From prebiotic chemistry to supramolecular biomedical materials: Exploring the properties of self-assembling nucleobase-containing peptides. Molecules 2021, 26, 3558.
62. Wang, H.; Feng, Z.; Xu, B. Supramolecular assemblies of peptides or nucleopeptides for gene delivery. Theranostics 2019, 9, 3213.
63. Wang, H.; Feng, Z.; Qin, Y.; Wang, J.; Xu, B. Nucleopeptide assemblies selectively sequester ATP in cancer cells to increase the efficacy of doxorubicin. Angew. Chem. 2018, 130, 5025–5029.
64. Ghosh, S.; Ghosh, T.; Bhowmik, S.; Patidar, M.K.; Das, A.K. Nucleopeptide-coupled injectable bioconjugated guanosine-quadruplex hydrogel with inherent antibacterial activity. ACS Appl. Bio Mater. 2023, 6, 640–651.
66. Baek, K.; Noblett, A.D.; Ren, P.; Suggs, L.J. Design and characterization of nucleopeptides for hydrogel self-assembly. ACS Appl. Bio Mater. 2019, 2, 2812–2821.
67. Zhang, Z.; Han, J.; Pei, Y.; Fan, R.; Du, J. Chaperone copolymer-assisted aptamer-patterned DNA hydrogels for triggering spatiotemporal release of protein. ACS Appl. Bio Mater. 2018, 1, 1206–1214.
68. Morán, M.C.; Infante, M.R.; Miguel, M.G.; Lindman, B.; Pons, R. Novel biocompatible DNA gel particles. Langmuir 2010, 26, 10606–10613.
70. Wei, Y.; Wang, K.; Luo, S.; Li, F.; Zuo, X.; Fan, C.; Li, Q. Programmable DNA hydrogels as Artificial extracellular matrix. Small 2022, 18, 2107640.
71. Ma, G.; Zhang, K.; Wang, H.; Liang, Z.; Zhou, L.; Yan, B. Versatile synthesis of a highly porous DNA/CNT hydrogel for the adsorption of the carcinogen PAH. Chem. Commun. 2021, 57, 2289–2292.
72. Bush, J.; Hu, C.-H.; Veneziano, R. Mechanical properties of DNA hydrogels: Towards highly programmable biomaterials. Appl. Sci. 2021, 11, 1885.
74. Yu, Y.; Nakamura, D.; DeBoyace, K.; Neisius, A.W.; McGown, L.B. Tunable thermoassociation of binary guanosine gels. J. Phys. Chem. B 2008, 112, 1130–1134.
75. Davis, J.T.; Spada, G.P. Supramolecular architectures generated by self-assembly of guanosine derivatives. Chem. Soc. Rev. 2007, 36, 296–313.
76. Longhi, G.; Castiglioni, E.; Koshoubu, J.; Mazzeo, G.; Abbate, S. Circularly polarized luminescence: A review of experimental and theoretical aspects. Chirality 2016, 28, 696–707.
77. Imai, Y. Generation of Circularly Polarized Luminescence by Symmetry Breaking. Symmetry 2020, 12, 1786.
78. Yang, G.; Zhang, S.; Hu, J.; Fujiki, M.; Zou, G. The chirality induction and modulation of polymers by circularly polarized light. Symmetry 2019, 11, 474.
79. Zou, C.; Qu, D.; Jiang, H.; Lu, D.; Ma, X.; Zhao, Z.; Xu, Y. Bacterial cellulose: A versatile chiral host for circularly polarized luminescence. Molecules 2019, 24, 1008.
80. Le Bideau, J.; Viau, L.; Vioux, A. Ionogels, ionic liquid based hybrid materials. Chem. Soc. Rev. 2011, 40, 907–925.
81. Qi, P.; Li, X.; Huang, Z.; Liu, Y.; Song, A.; Hao, J. G-quadruplex-based ionogels with controllable chirality for circularly polarized luminescence. Colloids Surf. A Physicochem. Eng. Asp. 2021, 629, 127411.
82. Li, Y.; Chi, J.; Xu, P.; Dong, X.; Le, A.-T.; Shi, K.; Liu, Y.; Xiao, J. Supramolecular G-quadruplex hydrogels: Bridging fabrication to biomedical application. J. Mater. Sci. Technol. 2023, 155, 238-252.
83. Fang, J.; Zheng, L.; Liu, Y.; Peng, Y.; Yang, Q.; Huang, Y.; Zhang, J.; Luo, L.; Shen, D.; Tan, Y. Smart G-quadruplex hydrogels: From preparations to comprehensive applications. Int. J. Biol. Macromol. 2023, 247, 125614.
84. Roxo, C.; Kotkowiak, W.; Pasternak, A. G-quadruplex-forming aptamers—Characteristics, applications, and perspectives. Molecules 2019, 24, 3781.
85. Bidzinska, J.; Cimino-Reale, G.; Zaffaroni, N.; Folini, M. G-quadruplex structures in the human genome as novel therapeutic targets. Molecules 2013, 18, 12368–12395.
86. Asamitsu, S.; Obata, S.; Yu, Z.; Bando, T.; Sugiyama, H. Recent progress of targeted G-quadruplex-preferred ligands toward cancer therapy. Molecules 2019, 24, 429.
87. Alessandrini, I.; Recagni, M.; Zaffaroni, N.; Folini, M. On the road to fight cancer: The potential of G-quadruplex ligands as novel therapeutic agents. Int. J. Mol. Sci. 2021, 22, 5947.
88. Santos, T.; Salgado, G.F.; Cabrita, E.J.; Cruz, C. G-quadruplexes and their ligands: Biophysical methods to unravel G-quadruplex/ligand interactions. Pharmaceuticals 2021, 14, 769.
89. Ruggiero, E.; Zanin, I.; Terreri, M.; Richter, S.N. G-quadruplex targeting in the fight against viruses: An update. Int. J. Mol. Sci. 2021, 22, 10984.
90. Marzano, M.; Falanga, A.P.; Marasco, D.; Borbone, N.; D’Errico, S.; Piccialli, G.; Roviello, G.N.; Oliviero, G. Evaluation of an analogue of the marine ε-PLL peptide as a ligand of G-quadruplex DNA structures. Mar. Drugs 2020, 18, 49.
91. Tanaka, S.; Yukami, S.; Hachiro, Y.; Ohya, Y.; Kuzuya, A. Application of DNA quadruplex hydrogels prepared from polyethylene glycol-oligodeoxynucleotide conjugates to cell culture media. Polymers 2019, 11, 1607.
92. Huang, Z.; Kangovi, G.N.; Wen, W.; Lee, S.; Niu, L. An RNA aptamer capable of forming a hydrogel by self-assembly. Biomacromolecules 2017, 18, 2056–2063.
94. Han, S.; Park, Y.; Kim, H.; Nam, H.; Ko, O.; Lee, J.B. Double controlled release of therapeutic RNA modules through injectable DNA–RNA hybrid hydrogel. ACS Appl. Mater. Interfaces 2020, 12, 55554–55563.
95. Brown, J.A. Unraveling the structure and biological functions of RNA triple helices. Wiley Interdiscip. Rev. RNA 2020, 11, e1598.
96. Conrad, N.K. The emerging role of triple helices in RNA biology. Wiley Interdiscip. Rev. RNA 2014, 5, 15–29.
97. Maldonado, R.; Längst, G. The chromatin–triple helix connection. Biol. Chem. 2023, 404, 1037–1049.
98. Conde, J.; Oliva, N.; Atilano, M.; Song, H.S.; Artzi, N. Self-assembled RNA-triple-helix hydrogel scaffold for microRNA modulation in the tumour microenvironment. Nat. Mater. 2016, 15, 353–363.
99. Li, J.; Yuan, D.; Zheng, X.; Zhang, X.; Li, X.; Zhang, S. A triple-combination nanotechnology platform based on multifunctional RNA hydrogel for lung cancer therapy. Sci. China Chem. 2020, 63, 546–553.
100. Wang, W.; Liu, X.; Ding, L.; Jin, H.J.; Li, X. Rna hydrogel combined with MnO2 nanoparticles as a nano-vaccine to treat triple negative breast cancer. Front. Chem. 2021, 9, 797094.
101. Ma, Y.; Duan, X.; Huang, J. DNA Hydrogels as Functional Materials and Their Biomedical Applications. Adv. Funct. Mater. 2023, 2309070.
Dancing with Nucleobases: Unveiling the Self-Assembly Properties of DNA and RNA Base-Containing Molecules for Gel Formation
Nucleobase-containing molecules are compounds essential in biology due to the fundamental role of nucleic acids and, in particular, G-quadruplex DNA and RNA in life. Moreover, some molecules different from nucleic acids isolated from different vegetal sources or microorgan-isms show nucleobase moieties in their structure. Nucleoamino acids and peptidyl nucleo-sides belong to this molecular class. Closely related to the above, nucleopeptides, also known as nucleobase-bearing peptides, are chimeric derivatives of synthetic origin and more rarely isolated from plants. Herein, the self-assembly properties of a vast number of structures, be-longing to the nucleic acid and nucleoamino acid/nucleopeptide family, are explored in light of the recent scientific literature. Moreover, several technologically relevant properties, such as the hydrogelation ability of some of the nucleobase-containing derivatives, are reviewed in order to make way for future experimental investigations of newly devised nucleo-base-driven hydrogels. Nucleobase-containing molecules, such as mononucleosides, DNA, RNA, quadruplex (G4)-forming oligonucleotides, and nucleopeptides are paramount in gel and hydrogel formation owing to their distinctive molecular attributes and ability to self-assemble in biomolecular nanosystems with the most diverse applications in different fields of biomedicine and nanotechnology. In fact, these molecules and their gels present nu-merous advantages, underscoring their significance and applicability in both material science and biomedicine. Their versatility, capability for molecular recognition, responsiveness to stimuli, biocompatibility, and biodegradability collectively contribute to their prominence in modern nanotechnology and biomedicine. In this review, we emphasize the critical role of nucleobase-containing molecules of different nature in pioneering novel materials with mul-tifaceted applications, highlighting their potential in therapy, diagnostics, and new nano-materials fabrication as required for addressing numerous current biomedical and nanotech-nological challenges.
Dancing with Nucleobases: Unveiling the Self-Assembly Properties of DNA and RNA Base-Containing Molecules for Gel Formation