Rational Design of a Cytotoxic Dinuclear Cu2Complex That Binds by Molecular Recognition at Two Neighboring Phosphates of the DNA Backbone

AbstractThe specific interactions responsible for molecular recognition play a crucial role in the fundamental functions of biological systems. Mimicking these interactions remains one of the overriding challenges for advances in both fundamental research in biochemistry and applications in material science. However, current molecular recognition systems based on host–guest supramolecular chemistry rely on familiar platforms (e.g., cyclodextrins, crown ethers, cucurbiturils, calixarenes, etc.) for orienting functionality. These platforms limit the opportunity for diversification of function, especially considering the vast demands in modern material science. Rational design of novel receptor-like systems for both biological and chemical recognition is important for the development of diverse functional materials. In this review, we focus on recent progress in chemically designed molecular recognition and their applications in material science. After a brief introduction to representative strategies, we describe selected advances in these emerging fields. The developed functional materials with dynamic properties including molecular assembly, enzyme-like and bio-recognition abilities are highlighted. We have also selected materials with dynamic properties in contract to traditional supramolecular host–guest systems. Finally, the current limitations and some future trends of these systems are discussed.

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CYTOTOXICITY OF POLYAMINE ANALOGS IS DIRECTLY RELATED TO THEIR DNA AFFINITY AS DETERMINED BY POLYACRYLAMIDE GEL COELECTROPHORESIS (PACE) METHOD

Journal of Biological System ◽

10.1142/s0218339004001282 ◽

2004 ◽

Vol 12 (04) ◽

pp. 387-397

Author(s):

SUBHRA BHATTACHARYA ◽

APARAJITA SARKAR ◽

BENJAMIN FRYDMAN ◽

HIRAK S. BASU

Keyword(s):

Tumor Cell ◽

Rational Design ◽

Human Tumor ◽

Dna Interaction ◽

Polyacrylamide Gel ◽

Simple Method ◽

Dna Backbone ◽

Novel Method ◽

Chain Lengths ◽

Polyamine Analogs

Polyamines are essential for cell growth. Polyamine analogs that can replace intracellular polyamines inhibit tumor cell proliferation both in culture as well as in animal models. The positively charged polyamines interact with the negatively charged DNA backbone both in a nonspecific manner, as well as sequence specifically through direct or water mediated hydrogen bonds. Therefore, it is difficult to ascertain the exact interactions that regulate the biological functions of polyamines. Several attempts have been made to determine the thermodynamic parameters of polyamine-DNA interactions with conflicting results. Here, we report a simple method of determining the apparent association constants for polyamine-DNA interaction by using polyacrylamide gel coelectrophoresis (PACE). We have used several cytotoxic polyamine analogs of different conformations and chain lengths. We observed that polyamine analogs with higher charge density or with conformational restrictions, which are absent in the naturally occurring polyamines, interact with DNA more strongly than do natural polyamines. A comparison of the cytotoxicities of the polyamine analogs against human tumor cell lines with their DNA affinities revealed that the higher the DNA affinity the more the cytoxicity of the analogs. The direct correlation between DNA affinities and cytotoxities provides a novel method for a rational design of therapeutically effective cytotoxic polyamine analogs.

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Gripping stuff: Allosteric ribozymes

The Biochemist ◽

10.1042/bio02802017 ◽

2006 ◽

Vol 28 (2) ◽

pp. 17-20

Author(s):

Andrea Rentmeister ◽

Michael Famulok

Keyword(s):

Catalytic Activity ◽

Molecular Recognition ◽

Ligand Binding ◽

Small Molecules ◽

Real Time ◽

Molecular Interactions ◽

Rational Design ◽

Signal Generation ◽

Selection Strategies ◽

Different Types

Allosteric ribozymes combine the features of ligand-binding aptamers with the catalytic activity of ribozymes and can be generated by rational design or diverse selection strategies. Their activity can be controlled by different types of effectors, ranging from small molecules to oligonucleotides and proteins. This direct coupling of molecular recognition to signal generation in real time allows the generation of versatile reporters that can be applied to report molecular interactions.

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Rational Design, Synthesis, and Application of a New Receptor for the Molecular Recognition of Tricarboxylate Salts in Aqueous Media

The Journal of Organic Chemistry ◽

10.1021/jo0609327 ◽

2006 ◽

Vol 71 (19) ◽

pp. 7185-7195 ◽

Cited By ~ 58

Author(s):

Antonio Frontera ◽

Jeroni Morey ◽

Antònia Oliver ◽

M. Neus Piña ◽

David Quiñonero ◽

...

Keyword(s):

Molecular Recognition ◽

Rational Design ◽

Aqueous Media ◽

Design Synthesis

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Transcription factor/DNA interactions visualized by electron spectroscopic imaging

Proceedings, annual meeting, Electron Microscopy Society of America ◽

10.1017/s0424820100122654 ◽

1992 ◽

Vol 50 (1) ◽

pp. 450-451

Author(s):

David P. Bazett-Jones ◽

Mark L. Brown

Keyword(s):

Transcription Factor ◽

Dna Sequences ◽

Transcription Initiation ◽

Molecular Mechanisms ◽

Phosphorus Content ◽

Spectroscopic Imaging ◽

Electron Spectroscopic Imaging ◽

Dna Backbone ◽

Two Parameters ◽

High Level

A multisubunit RNA polymerase enzyme is ultimately responsible for transcription initiation and elongation of RNA, but recognition of the proper start site by the enzyme is regulated by general, temporal and gene-specific trans-factors interacting at promoter and enhancer DNA sequences. To understand the molecular mechanisms which precisely regulate the transcription initiation event, it is crucial to elucidate the structure of the transcription factor/DNA complexes involved. Electron spectroscopic imaging (ESI) provides the opportunity to visualize individual DNA molecules. Enhancement of DNA contrast with ESI is accomplished by imaging with electrons that have interacted with inner shell electrons of phosphorus in the DNA backbone. Phosphorus detection at this intermediately high level of resolution (≈lnm) permits selective imaging of the DNA, to determine whether the protein factors compact, bend or wrap the DNA. Simultaneously, mass analysis and phosphorus content can be measured quantitatively, using adjacent DNA or tobacco mosaic virus (TMV) as mass and phosphorus standards. These two parameters provide stoichiometric information relating the ratios of protein:DNA content.

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Molecular insights on the dynamic stability of peptide nucleic acid functionalized carbon and boron nitride nanotubes

Physical Chemistry Chemical Physics ◽

10.1039/d0cp05759b ◽

2021 ◽

Vol 23 (1) ◽

pp. 219-228

Author(s):

Nabanita Saikia ◽

Mohamed Taha ◽

Ravindra Pandey

Keyword(s):

Nucleic Acid ◽

Boron Nitride ◽

Nucleic Acids ◽

Dynamic Stability ◽

Peptide Nucleic Acid ◽

Rational Design ◽

Peptide Nucleic Acids ◽

Boron Nitride Nanotubes ◽

Molecular Hybrids ◽

Single Wall Nanotubes

The rational design of self-assembled nanobio-molecular hybrids of peptide nucleic acids with single-wall nanotubes rely on understanding how biomolecules recognize and mediate intermolecular interactions with the nanomaterial's surface.

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