7-Deaza-7-Iodo-2'-deoxyadenosine is a synthetic analog of the natural DNA nucleoside 2'-deoxyadenosine (dA). It features two key modifications to the adenine base:
7-Deaza Modification: The carbon atom at position 7 (C7) of the purine ring is replaced by a nitrogen atom (N7). This disrupts the normal electron distribution and hydrogen bonding pattern of the base.
7-Iodo Modification: An iodine atom (I) is attached to the nitrogen now occupying position 7 (N7).
Here's a breakdown of its structure and significance:
Core Scaffold: 2'-Deoxyribose sugar (same as in natural DNA).
Base Modifications:
7-Deazaadenine: The base is 7-deazaadenine (also known as 7-aminopyrrolo[2,3-d]pyrimidine).
7-Iodo Substitution: The iodine atom is directly bonded to the N7 position of this modified base.
Chemical Formula: C₁₁H₁₃IN₄O₃
Molecular Weight: 376.15 g/mol
CAS Number: 133432-71-0
Key Properties and Applications (Primarily in Research):
Heavy Atom for Crystallography: The iodine atom acts as a "heavy atom," which is crucial for solving the phase problem in X-ray crystallography of nucleic acids. Its strong X-ray scattering helps determine the 3D structure of DNA or RNA containing this modified nucleoside.
Reactive Handle for Functionalization: The carbon-iodine (C-I) bond is relatively stable but can be selectively activated. This makes it a versatile handle for post-synthetic modification via cross-coupling reactions (like Sonogashira, Suzuki, Heck). Researchers can attach fluorophores, biotin, or other functional groups to specific sites within an oligonucleotide.
Photo-Crosslinking: Under UV irradiation (around 300-320 nm), the C-I bond can cleave homolytically, generating a highly reactive carbon-centered radical at position 7. This radical can rapidly form covalent bonds with nearby molecules (proteins, other nucleic acids), enabling photo-crosslinking studies to investigate nucleic acid interactions and structures.
Base Pairing Properties: The 7-deaza modification removes a key hydrogen bond acceptor (N7) involved in Hoogsteen base pairing and can subtly affect Watson-Crick pairing stability and specificity. The bulky iodine atom can cause steric hindrance. While it primarily pairs with thymine (T), its pairing efficiency and fidelity can be lower than natural dA, making it useful for studying polymerase recognition and fidelity.
Sequencing Applications: It has been explored in Sanger sequencing and other methods where chain termination or modified bases are used, sometimes to overcome issues like compression artifacts.
Enzyme Inhibition Studies: Can be used as a substrate analog to study the mechanisms of enzymes involved in nucleotide metabolism (kinases, polymerases) or DNA repair.
In Summary:
7-Deaza-7-Iodo-2'-deoxyadenosine is a chemically modified building block for DNA synthesis. Its core value lies in the iodine atom, which serves as both a heavy atom for X-ray crystallography and a versatile chemical handle for attachment of probes or for photo-crosslinking experiments. The 7-deaza modification facilitates these applications by providing the attachment point (N7) and altering the base's electronic properties. It is a valuable tool in structural biology, bioconjugation chemistry, and the study of nucleic acid interactions and enzymology.
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