Aptamer-guided acridine derivatives for cervical cancer

Carvalho, Josué; Lopes-Nunes, Jéssica; Lopes, A.; Campello, Maria Paula Cabral; Paulo, António; Queiroz, João A.; Cruz, Carla

doi:10.1039/c9ob00318e

Cited by 37 publications

(31 citation statements)

References 22 publications

Supporting

Mentioning

Contrasting

Order By: Relevance

“…This aptamer, named AT11, exhibited a similar antiproliferative activity as AS1411; however, additional studies are required to understand how this G4 may contribute to the cellular uptake and antiproliferative activity. Modification of AT11 by removing one thymine residue between the two G4 subunits leads to various sequence of the AT11-L0 aptamer, which forms a parallel-stranded G4 containing four G-quarters (Figure 2D) [85]. The conjugates of this aptamer with C3, C5, and C8 acridine derivatives demonstrated higher thermal stability than AT11 and AT11-L0.…”

Section: Anticancer Agentsmentioning

confidence: 99%

G-Quadruplex-Forming Aptamers—Characteristics, Applications, and Perspectives

2019

View full text Add to dashboard Cite

G-quadruplexes constitute a unique class of nucleic acid structures formed by G-rich oligonucleotides of DNA- or RNA-type. Depending on their chemical nature, loops length, and localization in the sequence or structure molecularity, G-quadruplexes are highly polymorphic structures showing various folding topologies. They may be formed in the human genome where they are believed to play a pivotal role in the regulation of multiple biological processes such as replication, transcription, and translation. Thus, natural G-quadruplex structures became prospective targets for disease treatment. The fast development of systematic evolution of ligands by exponential enrichment (SELEX) technologies provided a number of G-rich aptamers revealing the potential of G-quadruplex structures as a promising molecular tool targeted toward various biologically important ligands. Because of their high stability, increased cellular uptake, ease of chemical modification, minor production costs, and convenient storage, G-rich aptamers became interesting therapeutic and diagnostic alternatives to antibodies. In this review, we describe the recent advances in the development of G-quadruplex based aptamers by focusing on the therapeutic and diagnostic potential of this exceptional class of nucleic acid structures.

show abstract

Section: Anticancer Agentsmentioning

confidence: 99%

G-Quadruplex-Forming Aptamers—Characteristics, Applications, and Perspectives

2019

View full text Add to dashboard Cite

show abstract

“…G-quadruplexes have been extensively studied in recent years, and their various targets, such as cancer cells [ 6 , 7 , 8 , 9 ], viruses [ 10 , 11 , 12 ] and proteins [ 13 , 14 ], were revealed. In particular, G-rich oligonucleotides are perceived as cancer-selective antiproliferative agents [ 15 , 16 , 17 ]. One of the most studied anticancer aptamers and the most clinically advanced G-quadruplex is AS1411, first discovered by Bates et al [ 18 ].…”

Section: Introductionmentioning

confidence: 99%

G4 Matters—The Influence of G-Quadruplex Structural Elements on the Antiproliferative Properties of G-Rich Oligonucleotides

Roxo

Kotkowiak

Pasternak

2021

IJMS

View full text Add to dashboard Cite

G-quadruplexes (G4s) are non-canonical structures formed by guanine-rich sequences of DNA or RNA that have attracted increased attention as anticancer agents. This systematic study aimed to investigate the anticancer potential of five G4-forming, sequence-related DNA molecules in terms of their thermodynamic and structural properties, biostability and cellular uptake. The antiproliferative studies revealed that less thermodynamically stable G4s with three G-tetrads in the core and longer loops are more predisposed to effectively inhibit cancer cell growth. By contrast, highly structured G4s with an extended core containing four G-tetrads and longer loops are characterized by more efficient cellular uptake and improved biostability. Various analyses have indicated that the G4 structural elements are intrinsic to the biological activity of these molecules. Importantly, the structural requirements are different for efficient cancer cell line inhibition and favorable G4 cellular uptake. Thus, the ultimate antiproliferative potential of G4s is a net result of the specific balance among the structural features that are favorable for efficient uptake and those that increase the inhibitory activity of the studied molecules. Understanding the G4 structural features and their role in the biological activity of G-rich molecules might facilitate the development of novel, more potent G4-based therapeutics with unprecedented anticancer properties.

show abstract

“…12,13 These receptors called aptamers (a term with Latin and Greek origins: aptus meaning t and meros meaning part) have shown notable moldable selectivity for diverse target analytes, ranging from small inorganic molecules, ions, sugars, proteins, and viruses to cells. [14][15][16][17][18][19][20][21][22][23][24][25][26][27][28][29][30][31][32][33] Such a varied target range is lacking in antibody generation due to the restriction of target receptor exposure in their native forms. This is more evident in whole cells where the surface antigens contain certain hidden trans-membrane regions, a fact which is generally not accounted for during the maturation of antibodies.…”

Section: Introductionmentioning

confidence: 99%