Synthesis, physicochemical and biochemical properties of C3'-modified 2',5'-linked oligonucleotides
Bibliographic record
Abstract
Oligoribonucleotides comprising of 2',5' -linked internucleotide linkages are known to bind selectively to RNA over DNA. The ability to bind to RNA renders them suitable as probes for many biological applications, such as 'antisense technology'. Little is known about the effect of sugar structure (and conformation) on the binding properties of 2',5'-linked oligonucleotides. To get insight into the role of sugar conformation, 2 ',5'-linked oligonucleotides modified at the C3'-position of the furanose ring were synthesized via solid phase synthesis and their binding to complementary single stranded DNA and RNA was studied. Their application as antisense oligonucleotides was also evaluated. The first analogue studied was the C3'-epimer of 2',5'-linked ribonucleic acids (2 ',5'-RNA), that is, an oligonucleotide in which the ribofuranose sugar is replaced by xylofuranose (2' ,5'-XNA). This was followed by the synthesis and analysis of the C3'-fluorinated xylofuranose analogue (2',5'-FXNA). The sugar conformation in these oligonucleotides are believed to have a very high population of the C3'-endo ('extended') conformation. Consistent with this notion, CD structural studies indicated that 2 ',5,'-linked XNA and FXNA show structural similarities to the 'extended' C2'- endo form of DNA. We found that both 2',5 '-XNA and 2',5'-FXNA bound weakly to complementary single stranded DNA and RNA. Neither of the xylooligomers resulted in RNaseH activated degradation of RNA. The last modified oligonucleotide to be studied was the C3' -fluorinated-2',5'-linked ribonucleic acids (2',5'-FRNA), which has a compact C2'-endo sugar conformation. In contrast to 2',5'-FXNA, 2 ',5'-FRNA bound strongly to complementary oligonucleotides and showed structural similarities to RNA (CD spectroscopy). Our studies showed that it did not cause RNaseH based degradation of RNA. These studies are consistent with the notion that the effect of sugar conformation in 2',5'-oligonucleotides is opposite to that of 3',5'-oligonucleotides. In other words, a C3'-endo sugar conformation in 2',5'-oligomers renders the oligonucleotide as 'extended' and portrays itself equivalent to the 'extended' DNA conformation (which has C2'-endo conformation), whereas a C2'-endo 2 ',5'-oligonucleotide adopts a 'compact' conformation that is equivalent to that seen in 3',5 '-oligonucleotides adopting the C3'- endo pucker (e.g. RNA).
Fetched live from OpenAlex and de-inverted. Abstracts are not stored in this database: the inverted indexes are 8.6 GB of the frame’s 9.3 GB of text, and the host has 13 GB free.
How this classification was reachedexpand
Full frame machine prediction
Teacher imitationNot calibrated prevalence, not ground truth. Human validation pending. The Gemma side is a direct model label for every work in the frame, read from the title-only record. The Codex side is a classifier learned from the 10,348 direct Codex labels and calibrated to design-weighted sample rates; fields without enough sample support carry no Codex call. Candidate is the union of the two sides; consensus is their intersection. These outputs are machine_predicted_unvalidated and are not human labels.
Distilled classifier scores by category (both heads)
| Category | Codex | Gemma |
|---|---|---|
| Metaresearch | 0.000 | 0.000 |
| Meta-epidemiology (narrow) | 0.000 | 0.000 |
| Meta-epidemiology (broad) | 0.000 | 0.000 |
| Bibliometrics | 0.000 | 0.000 |
| Science and technology studies | 0.000 | 0.000 |
| Scholarly communication | 0.000 | 0.000 |
| Open science | 0.000 | 0.000 |
| Research integrity | 0.000 | 0.000 |
| Insufficient payload (model declined to judge) | 0.001 | 0.000 |
Machine scores (provisional)
The two teacher heads of the student model, read on this work. A score orders the frame for review; it never asserts a category, and the validation status ships verbatim with every row.
Baseline scores from an immature model (maturity gate not passed, 7 training rounds). Scores rank; they never assert a category.
score_only:v0-immature-baseline · verbatim from the scoring run: score_only means the number may rank works, and no category label ships from itClassification
machine, unvalidatedMachine predicted; a candidate call from one source (direct Gemma or distilled Codex), not a consensus.
How this classification was reached, model by model and score by score, is at the end of the page under "How this classification was reached".