Synthesis of Small Molecules Targeting Multiple DNA Structures using Click Chemistry

ChemMedChem ◽  
2012 ◽  
Vol 7 (5) ◽  
pp. 792-804 ◽  
Author(s):  
Lesley A. Howell ◽  
Richard A. Bowater ◽  
Maria A. O'Connell ◽  
Anthony P. Reszka ◽  
Stephen Neidle ◽  
...  
Keyword(s):  
Small Molecules ◽  
Click Chemistry ◽  
Dna Structures

scholarly journals N-methyl mesoporphyrin IX as a highly selective light-up probe for G-quadruplex DNA

2019 ◽  
Vol 23 (11n12) ◽  
pp. 1195-1215 ◽  
Author(s):  
Ariana Yett ◽  
Linda Yingqi Lin ◽  
Dana Beseiso ◽  
Joanne Miao ◽  
Liliya A. Yatsunyk
Keyword(s):  
Optical Properties ◽  
Small Molecules ◽  
Genomic Stability ◽  
Water Soluble ◽  
Biological Processes ◽  
Binding Properties ◽  
Quadruplex Dna ◽  
Dna Structures ◽  
G Quadruplex ◽  
High Fluorescence

[Formula: see text]-methyl mesoporphyrin IX (NMM) is a water-soluble, non-symmetric porphyrin with excellent optical properties and unparalleled selectivity for G-quadruplex (GQ) DNA. G-quadruplexes are non-canonical DNA structures formed by guanine-rich sequences. They are implicated in genomic stability, longevity, and cancer. The ability of NMM to selectively recognize GQ structures makes it a valuable scaffold for designing novel GQ binders. In this review, we survey the literature describing the GQ-binding properties of NMM as well as its wide utility in chemistry and biology. We start with the discovery of the GQ-binding properties of NMM and the development of NMM-binding aptamers. We then discuss the optical properties of NMM, focusing on the light-switch effect — high fluorescence of NMM induced upon its binding to GQ DNA. Additionally, we examine the affinity and selectivity of NMM for GQs, as well as its ability to stabilize GQ structures and favor parallel GQ conformations. Furthermore, a portion of the review is dedicated to the applications of NMM-GQ complexes as biosensors for heavy metals, small molecules ([Formula: see text] ATP and pesticides), DNA, and proteins. Finally and importantly, we discuss the utility of NMM as a probe to investigate the roles of GQs in biological processes.

One pot conjugation of small molecules to RNA using click chemistry

2012 ◽  
Vol 53 (50) ◽  
pp. 6747-6750 ◽  
Author(s):  
Wei Wang ◽  
Ke Chen ◽  
Dezhong Qu ◽  
Weilin Chi ◽  
Wei Xiong ◽  
...  
Keyword(s):  
Small Molecules ◽  
Click Chemistry ◽  
One Pot

Differences in affinity of arylstilbazolium derivatives to tetraplex structures

2011 ◽  
Vol 65 (2) ◽  
Author(s):  
Izabella Czerwinska ◽  
Bernard Juskowiak
Keyword(s):  
Small Molecules ◽  
Therapeutic Agent ◽  
Equilibrium Dialysis ◽  
Structural Features ◽  
Acid Number ◽  
Strong Interactions ◽  
Dna Structures ◽  
G Quadruplex ◽  
Preferential Binding ◽  
Important Field

AbstractResearch into the interactions of small molecules (ligands) with DNA is a very important field of biochemistry. A ligand interacts with a DNA structure in many ways, depending on the structural features of the ligand (the presence of rings, substituent groups, length of bonds, etc.) or nucleic acid (number and association of strands, base sequence etc.). This study reports on an investigation of the preferential binding of arylstilbazolium ligands to a four-stranded DNA. For this purpose, an equilibrium dialysis was used. Equilibrium dialysis is a versatile method which enables many DNA structures to be investigated at the same time. A dozen different DNA structures of (single-stranded, double-stranded (duplex), triple-stranded (triplex), and four-stranded (tetraplex)) were involved in experiments with each ligand. Following the dissociation of DNA-ligand complexes by SDS, the concentration of the ligand bound was calculated from fluorescence and absorbance calibration curves. As a result, the amount of the ligand bound was directly related to the ligand-binding affinity. Equilibrium dialysis was used as a powerful tool to indicate which of the arylstilbazolium ligands investigated was the best therapeutic agent targeting G-quadruplex. Arylstilbazolium derivatives demonstrated strong interactions with the DNA samples used in the assay. The most interesting finding was a selective, preferential binding of anthryl derivative to c-MYC DNA (c-MYC is a DNA sequence that appears in an oncogene). Furthermore, as this derivative binds preferentially to one of the triplexes investigated, it can find an application in the TFO-triplex forming oligonucleotides which are used in gene therapy.

scholarly journals Light-induced primary amines and o-nitrobenzyl alcohols cyclization as a versatile photoclick reaction for modular conjugation

2020 ◽  
Vol 11 (1) ◽  
Author(s):  
An-Di Guo ◽  
Dan Wei ◽  
Hui-Jun Nie ◽  
Hao Hu ◽  
Chengyuan Peng ◽  
...  
Keyword(s):  
Small Molecules ◽  
Click Chemistry ◽  
Chemical Biology ◽  
Materials Science ◽  
Primary Amines ◽  
Mild Conditions ◽  
Native Proteins ◽  
Good Biocompatibility ◽  
Operational Simplicity

Abstract The advent of click chemistry has had a profound impact on many fields and fueled a need for reliable reactions to expand the click chemistry toolkit. However, developing new systems to fulfill the click chemistry criteria remains highly desirable yet challenging. Here, we report the development of light-induced primary amines and o-nitrobenzyl alcohols cyclization (PANAC) as a photoclick reaction via primary amines as direct click handle, to rapid and modular functionalization of diverse small molecules and native biomolecules. With intrinsic advantages of temporal control, good biocompatibility, reliable chemoselectivity, excellent efficiency, readily accessible reactants, operational simplicity and mild conditions, the PANAC photoclick is robust for direct diversification of pharmaceuticals and biorelevant molecules, lysine-specific modifications of unprotected peptides and native proteins in vitro, temporal profiling of endogenous kinases and organelle-targeted labeling in living systems. This strategy provides a versatile platform for organic synthesis, bioconjugation, medicinal chemistry, chemical biology and materials science.

Versatile Site-Specific Conjugation of Small Molecules to siRNA Using Click Chemistry

2011 ◽  
Vol 76 (5) ◽  
pp. 1198-1211 ◽  
Author(s):  
Takeshi Yamada ◽  
Chang Geng Peng ◽  
Shigeo Matsuda ◽  
Haripriya Addepalli ◽  
K. Narayanannair Jayaprakash ◽  
...  
Keyword(s):  
Small Molecules ◽  
Click Chemistry ◽  
Site Specific

CuI NPs Facilitated Click Chemistry for the Late-Stage Diversification of Bioactive Complex Small Molecules

2019 ◽  
Author(s):  
rahul upadhyay ◽  
Rahul Kumar ◽  
Rohit Rana ◽  
Onkar S. Nayal ◽  
Sushil K. Maurya
Keyword(s):  
Small Molecules ◽  
Click Chemistry ◽  
Late Stage

scholarly journals Stage-Specific and Selective Delivery of Caged Azidosugars into the Intracellular Parasite Toxoplasma gondii by Using an Esterase-Ester Pair Technique

mSphere ◽  
2019 ◽  
Vol 4 (3) ◽  
Author(s):  
Tadakimi Tomita ◽  
Hua Wang ◽  
Peng Wu ◽  
Louis M. Weiss
Keyword(s):  
Toxoplasma Gondii ◽  
Small Molecules ◽  
Click Chemistry ◽  
Cell Biology ◽  
Host Cells ◽  
Intracellular Parasite ◽  
Content Type ◽  
Intracellular Parasites ◽  
Specific Manner ◽  
Selective Delivery

ABSTRACT Toxoplasma gondii is an obligate intracellular parasite that chronically infects up to a third of the human population. The parasites persist in the form of cysts in the central nervous system and serve as a reservoir for the reactivation of toxoplasmic encephalitis. The cyst wall is known to have abundant O-linked N-acetylgalactosamine glycans, but the existing metabolic labeling methods do not allow selective labeling of intracellular parasite glycoproteins without labeling of host glycans. In this study, we have integrated Cu(I)-catalyzed bioorthogonal click chemistry with a specific esterase-ester pair system in order to selectively deliver azidosugars to the intracellular parasites. We demonstrated that α-cyclopropyl modified GalNAz was cleaved by porcine liver esterase produced in the parasites but not in the host cells. Our proof-of-concept study demonstrates the feasibility and potential of this esterase-ester click chemistry approach for the selective delivery of small molecules in a stage-specific manner. IMPORTANCE Selective delivery of small molecules into intracellular parasites is particularly problematic due to the presence of multiple membranes and surrounding host cells. We have devised a method that can deliver caged molecules into an intracellular parasite, Toxoplasma gondii, that express an uncaging enzyme in a stage-specific manner without affecting host cell biology. This system provides a valuable tool for studying many intracellular parasites.

scholarly journals Metal-Based G-Quadruplex Binders for Cancer Theranostics

2021 ◽  
Vol 14 (7) ◽  
pp. 605
Author(s):  
Elisa Palma ◽  
Josué Carvalho ◽  
Carla Cruz ◽  
António Paulo
Keyword(s):  
Nuclear Medicine ◽  
Metal Complexes ◽  
Small Molecules ◽  
Significant Progress ◽  
Comprehensive Overview ◽  
Dna Structures ◽  
Potential Interest ◽  
G Quadruplex ◽  
Theranostic Agents ◽  
Cancer Theranostics

The ability of fluorescent small molecules, such as metal complexes, to selectively recognize G-quadruplex (G4) structures has opened a route to develop new probes for the visualization of these DNA structures in cells. The main goal of this review is to update the most recent research efforts towards the development of novel cancer theranostic agents using this type of metal-based probes that specifically recognize G4 structures. This encompassed a comprehensive overview of the most significant progress in the field, namely based on complexes with Cu, Pt, and Ru that are among the most studied metals to obtain this class of molecules. It is also discussed the potential interest of obtaining G4-binders with medical radiometals (e.g., 99mTc, 111In, 64Cu, 195mPt) suitable for diagnostic and/or therapeutic applications within nuclear medicine modalities, in order to enable their theranostic potential.

scholarly journals Molecular population dynamics of DNA structures in a bcl-2 promoter sequence is regulated by small molecules and the transcription factor hnRNP LL

2014 ◽  
Vol 42 (9) ◽  
pp. 5755-5764 ◽  
Author(s):  
Yunxi Cui ◽  
Deepak Koirala ◽  
HyunJin Kang ◽  
Soma Dhakal ◽  
Philip Yangyuoru ◽  
...  
Keyword(s):  
Population Dynamics ◽  
Transcription Factor ◽  
Small Molecules ◽  
Promoter Sequence ◽  
Dna Structures
Sign in / Sign up

Export Citation Format

Share Document