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Polypurine reverse-Hoogsteen hairpin

Polypurine reverse-Hoogsteen hairpin is a chemistry topic covered in the lgStudy science library. This page brings together a partial reference excerpt, illustrations, worked examples, real-world applications and a short study plan, so you can understand Polypurine reverse-Hoogsteen hairpin rather than just read about it. In short: Polypurine reverse-Hoogsteen hairpins (PPRHs) are non-modified oligonucleotides containing two polypurine domains, in a mirror repeat fashion, linked by a pentathymidine stretch forming double-stranded DNA stem-loop molecules. The two polypurine domains interact by intramolecular reverse-Hoogsteen bonds allowing the formation of this specific hairpin structure.

Polypurine reverse-Hoogsteen hairpin — main illustration
Polypurine reverse-Hoogsteen hairpin — illustration

Key takeaways

  • Polypurine reverse-Hoogsteen hairpin belongs to chemistry; place it in that map before memorising details.
  • Learn the definition first, then one example that makes the definition concrete.
  • Connect Polypurine reverse-Hoogsteen hairpin to a quantity you can measure, compute or draw — that is where exam questions come from.
  • Reproduce the core statement of Polypurine reverse-Hoogsteen hairpin from memory before moving on to harder problems.

Reference excerpt

Polypurine reverse-Hoogsteen hairpins (PPRHs) are non-modified oligonucleotides containing two polypurine domains, in a mirror repeat fashion, linked by a pentathymidine stretch forming double-stranded DNA stem-loop molecules. The two polypurine domains interact by intramolecular reverse-Hoogsteen bonds allowing the formation of this specific hairpin structure.

Properties

PPRHs can bind to polypyrimidine stretches in either single- or double stranded DNA by Watson and Crick bonds establishing triple-stranded DNA structures. The formation of PPRHs triplexes takes place at physiological pH. PPRHs provoke a strand displacement. of the homopurine sequence of the target dsDNA, opening the two strands of the DNA. There are two types of PPRHs: i) Template-PPRHs that bind to the template strand of DNA, inhibiting transcription; and ii) Coding-PPRHs that bind to the coding strand of the DNA altering splicing. Both types of PPRHs decrease gene expression. PPRHs present high stability in serum and cells and show lack of immunogenicity not activating the innate inflammatory response. PPRHs do not have off-target effects and do not show hepatotoxicity or nephrotoxicity.

Applications PPRHs could be used as gene silencing tools acting by different mechanisms than triplex forming oligonucleotides (TFOs), antisense oligonucleotides or siRNAs. Upon binding to their targets, PPRHs can decrease the mRNA and protein levels of the selected genes. Their action has been demonstrated in vitro for a number of genes involved in metabolism (DHFR), proliferation (mTOR), DNA topology (TOP1), lifespan and senescence (telomerase), apoptosis (survivin, BCL2), transcription factors and non-druggable targets (c-MYC and k-Ras) , proto-oncogenes (MDM2), replication stress (WEE1, CHK1) and Thymidilate synthase (TYMS) as part of a cancer gene therapy strategy. Their preclinical proof of principle has been proven in vivo using the antiapoptotic survivin gene. PPRHs have also been applied as tools in cancer immunotherapy by silencing CD47 in MCF7 breast cancer cells and SIRPα in macrophages, and the PD-1/PD-L1 pathway in human tumor cells. PPRHs can also be used as the capture probe in different devises to detect viral infection by forming a triplex with the RNA of the virus such as SARS-CoV-2 in a technology termed Triplex Enhanced Nucleic Acid Detection Assay (TENADA)

Design and improvements

PPRHs can be designed for virtually any gene in the genome by searching for polypirimidine stretches in the sequence of the desired gene. Optimal lengths for each domain of the PPRHs are within 20–30 nucleotides. The total length of a typical PPRH is 55 nucleotides considering two domains of 25 bases plus 5T for the linking loop. If purine interruptions are encountered (up to three) within the polypirimidine target, the highest affinity of PPRH binding is achieved by placing in the hairpin the complementary base (a pyrimidine) in front of the purines (Wild type-PPRH).

Wedge-PPRH A further development consists in extending the 5' flank of the PPRH with a sequence complementary to the displaced polypurine strand of the target dsDNA which stabilizes the strand displacement, producing additional binding and functionality.

WEB tools A triplex target DNA site (TTS), a stretch of DNA that is composed of polypurines, is able to form a triple-helix (triplex) structure in genomic DNA. Integrative WEB tools for identification and analysis of the triplex formation target DNA sequences, including PPRH sequences, associated with genes and regulatory elements (e.g., transcription factor binding sites, repeats, G-quadruplet motifs, SNPs, and non-protein coding regulatory DNA elements) in the human genome are publicly available (see External links). These tools could be used to search biologically meaningful genome polypurine stretches, help to understand biological roles of the natural paired polypurine domains like PPRH and to optimize experimental design of anti-gene treatment.

References

External links

Illustrations

Polypurine reverse-Hoogsteen hairpin: PPRH structure showing the two homopurine domains bound by Reverse Hoogsteen bonds
PPRH structure showing the two homopurine domains bound by Reverse Hoogsteen bonds
Polypurine reverse-Hoogsteen hairpin: Template-PPRHs bind to the template strand of the dsDNA. Coding-PPRHs bind to the coding strand of the dsDNA
Template-PPRHs bind to the template strand of the dsDNA. Coding-PPRHs bind to the coding strand of the dsDNA
Polypurine reverse-Hoogsteen hairpin: Wild type-PPRH: Version of PPRH containing a pyrimidine in front of purine interruptions in the DNA target.
Wild type-PPRH: Version of PPRH containing a pyrimidine in front of purine interruptions in the DNA target.
Polypurine reverse-Hoogsteen hairpin: Wedge-PPRH: Specific type of PPRH with an extension on the 5' end bearing the complementary sequence of the displaced strand of the target dsDNA
Wedge-PPRH: Specific type of PPRH with an extension on the 5' end bearing the complementary sequence of the displaced strand of the target dsDNA

Worked examples

Example 1 — a first encounter with Polypurine reverse-Hoogsteen hairpin

Start with the simplest possible case. Write down what Polypurine reverse-Hoogsteen hairpin claims or describes in one sentence, then invent the smallest concrete situation in which that sentence is true. In chemistry, the smallest case is usually a single object, a single equation or a single measurement. Check that every symbol or term in your sentence has a meaning in that case.

Example 2 — changing one variable

Take the situation from Example 1 and change exactly one quantity: double it, halve it, or set it to zero. Predict what should happen to Polypurine reverse-Hoogsteen hairpin before you calculate. Comparing your prediction with the result is the fastest way to find out whether you understand the idea or only the words.

Example 3 — an exam-style question

Typical questions about Polypurine reverse-Hoogsteen hairpin ask you to (a) state it precisely, (b) apply it to given data, and (c) explain a limitation. Practise writing all three answers in under five minutes; the third part is what separates a full-mark answer from an average one.

Applications of Polypurine reverse-Hoogsteen hairpin

In research
Polypurine reverse-Hoogsteen hairpin appears in chemistry research whenever the underlying quantities have to be modelled precisely. Papers usually cite it as a starting assumption and then explore where it breaks down.
In technology and industry
Engineering practice reuses Polypurine reverse-Hoogsteen hairpin in design rules, simulations and safety margins. Knowing the idea lets you read a specification sheet and understand why the numbers look the way they do.
In the classroom
Polypurine reverse-Hoogsteen hairpin is common in secondary-school and first-year university syllabi. It links to neighbouring topics Nucleic acids, so understanding it makes those chapters shorter.
In everyday life
Look for Polypurine reverse-Hoogsteen hairpin outside the textbook — in sport, cooking, traffic, electronics or the sky above you. An example you found yourself is remembered far longer than one you were given.
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How to study Polypurine reverse-Hoogsteen hairpin in 20 minutes

  1. Read the reference excerpt below once, without taking notes.
  2. Close the page and write down what Polypurine reverse-Hoogsteen hairpin means in your own words.
  3. Compare your version with the excerpt and mark what you missed.
  4. Work through the three examples above with pen and paper.
  5. Explain Polypurine reverse-Hoogsteen hairpin out loud to somebody else — or to Teacher Smith in the lgStudy chat.

Frequently asked questions

What is Polypurine reverse-Hoogsteen hairpin in simple terms?

Polypurine reverse-Hoogsteen hairpins (PPRHs) are non-modified oligonucleotides containing two polypurine domains, in a mirror repeat fashion, linked by a pentathymidine stretch forming double-stranded DNA stem-loop molecules. The two polypurine domains interact by intramolecular reverse-Hoogsteen…

Why does Polypurine reverse-Hoogsteen hairpin matter?

Because it connects several chemistry ideas at once: it gives you a definition you can apply, a quantity you can calculate, and a way to check whether a result is plausible.

How should I study Polypurine reverse-Hoogsteen hairpin?

Read the excerpt, restate it from memory, then work through the examples and applications listed on this page. The five-step study plan above takes about twenty minutes.

What does this page cover?

It gives you a compact reference excerpt plus original lgStudy explanations, examples, applications and study material on Polypurine reverse-Hoogsteen hairpin.

Tags

  • Nucleic acids

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