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Post by skyship on Feb 15, 2010 16:33:10 GMT -5
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Post by aqt on Feb 15, 2010 16:59:00 GMT -5
sky, from your link interesting A molecule that some researchers study in pursuit of this vision is peptide nucleic acid (PNA), which mimics the information-storing features of DNA and RNA but is built on a proteinlike backbone that is simpler and sturdier than their sugar-phosphate backbones. PNA’s unique properties potentially give it several advantages over antisense DNAs and RNAs, including more versatility in binding to DNA as well as RNA, stronger binding to its target and greater chemical stability in the enzyme-laden cellular environment. heavenawaits.wordpress.com/satan-dna/
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Post by aqt on Feb 15, 2010 17:00:00 GMT -5
proteinlike backbone?
proteomics?
Proteome Research Center?
aqt
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Post by skyship on Feb 16, 2010 2:04:09 GMT -5
protein like backbone replaces the sugar backbone: the hybrid Structure of Hybrid Backbone Methylphosphonate DNA Heteroduplexes: Effect of R and S StereochemistryAbstract Methyl phosphonate oligonucleotides have been used as antisense and antigene agents. Substitution of a methyl group for oxygen in the phosphate ester backbone introduces a new chiral center. Significant differences in physical properties and hybridization abilities are observed between the Rp and Sp diastereomers. Chirally pure methylphosphonate deoxyribooligonucleotides were synthesized, and the solution structures of duplexes formed between a single strand heptanucleotide methylphosphonate, d(CpMeCpMeApMeApMeApMeCpMeA), hybridized to a complementary octanucleotide, d(TpGpTpTpTpGpGpC), were studied by NMR spectroscopy. Stereochemistry at the methylphosphonate center for the heptanucleotide was either RpRpRpRpRpRp (Rp stereoisomer) or RpRpRpSpRpRp (Sp stereoisomer, although only one of the six methylphosphonate centers has the Sp stereochemistry). The results show that the methylphosphonate strands in the heteroduplexes exhibit increased dynamics relative to the DNA strand. Substitution of one chiral center from Rp to Sp has a profound effect on the hybridization ability of the methylphosphonate strand. Sugars in the phosphodiester strand exhibit C2‘ endo sugar puckering while the sugars in the methyl phosphonate strand exhibit an intermediate C4‘ endo puckering. Bases are well stacked on each other throughout the duplex. The hybridization of the methylphosphonate strand does not perturb the structure of the complementary DNA strand in the hetero duplexes. The sugar residue 5‘ to the Sp chiral center shows A-form sugar puckering, with a C3‘-endo conformation. Minor groove width in the Rp stereoisomer is considerably wider, particularly at the Rp vs Sp site and is attributed to either steric interactions across the minor groove or poorer metal ion coordination within the minor groove. pubs.acs.org/doi/abs/10.1021/bi011551k#bi011551kAF5=========================== Backbone modified oligonucleotide analogsOligonucleotide analogs are provided that have modified linkages which replace phosphorodiester bonds which normally serve as inter-sugar linkages in wild type nucleic acids. Such analogs are resistant to nuclease degradation and are capable of modulating the activity of DNA and RNA.www.freepatentsonline.com/5378825.htmlskyship
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Post by skyship on Feb 16, 2010 3:14:50 GMT -5
wonder how they overcame the skin penetration issue? series of antisense methyl phosphonate oligonucleotides (MPOs) were evaluated in vitro for skin penetration and retention using either hairless mouse or human cadaver skin. Several skin penetration enhancers were used to promote uptake of MPOs ranging in molecular weight from 1834 to 5500. In general, as the molecular weight of the MPOs increased, the penetration rate decreased. Tape stripping experiments with both hairless mouse skin and human cadaver skin indicated that the stratum corneum is the primary barrier to penetration. Comparison of a 14-mer MPO and the same MPO modified by the introduction of one negative charge (phosphate linkage) per molecule reduced the skin permeability by about 10-fold cat.inist.fr/?aModele=afficheN&cpsidt=4112536======== wonder if that is on the janus particle? janus particle and the oligonucleotide? venters little creation? ============== s
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Post by skyship on Mar 21, 2010 23:33:39 GMT -5
Do not know what above means, goofy message? or is there hidden meaning? =============== Comparison of a 14-mer MPO and the same MPO modified by the introduction of one negative charge (phosphate linkage) per molecule reduced the skin permeability by about 10-foldthis means penetrates through skin, MPO's by inducing negative charge. ------------------------ called IontophoresisIontophoresis is a technique using a small electric charge to deliver a medicine or other chemical through the skin. Basically an injection without the needle.
============ The mechanism used?.....................That wouldn't be Haarp or Qwen towers or wireless, now would it? "MechanismThere are a number of factors that influence iontophoretic transport including skin pH, drug concentration and characteristics, ionic competition, molecular size, current, voltage, time applied and skin resistance. The current density of the treatment electrode is perhaps the most important variable relative to the degree of ion transfer. Studies suggest that comparable iontophoretic doses delivered at low currents over longer periods are more effective than those delivered by high currents over a short periods (Anderson et al., 2003)." right through the pore, hair shaft, etc anywhere, inside too!The isoelectric point of the skin is ~4; therefore, under physiological conditions, with the surface of the skin also buffered at or near 7.4, the membrane has a net negative charge and electroosmotic flow is from cathode (-) to anode (+). The phenomenon of electroosmosis has been used as a means to augment the anodic delivery of (in particular) large, positively charged drugs, the transport numbers of which are often extremely small (and whose iontophoretic enhancement therefore depends heavily upon electroosmosis) and to promote the transdermal migration of uncharged, yet polar, molecules, the passive permeation of which is typically very small. Passive permeation is very small, yep pore size.The application of a charge to the skin alters the skin’s permeability increasing migration of the active ingredient into the epidermis. There are a number of pathways that the ingredients could take, but research suggests that the majority of drugs permeate the skin via appendageal pores, including hair follicles and sweat glands, although some delivery is via the paracellular channels and minimal quantities are transcellular.en.wikipedia.org/wiki/IontophoresisElectroosmosis:Applications Vascular plant biology In vascular plant biology, electro-osmosis is also used as an alternative or supplemental explanation for the movement of polar liquids via the phloem that differs from the cohesion-tension theory supplied in the mass flow hypothesis and others, such as cytoplasmic streaming. [1] Principally, companion cells are involved in the "cyclic" withdrawal of ions (K + ) from sieve tubes, and their secretion parallel to their position of withdrawal between sieve plates, resulting in polarisation of sieve plate elements alongside potential difference in pressure, and results in polar water molecules and other solutes present being moved upwards through the phloem. [2][3] In 2003, St Petersburg University graduates based an experiment on the electro-osmosis hypothesis through the application of direct electric current to 10mm segments of mesocotyls of maize seedlings alongside one-year linden shoots used with normal conducting systems and without vascular bundles; electrolyte solutions present in the tissues moved towards the cathode that was in place, suggesting that electro-osmosis may play a role in solution transport through conductive plant tissues. [4] en.wikipedia.org/wiki/Electroosmosisso, if cathode is present in plants, could they not be present in animals, humans and soil?
Maybe not lithium, aqt? maybe cathodes? nano cathodes?
skyship
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Post by skyship on Mar 22, 2010 0:01:59 GMT -5
Enter in the d"Chirally pure dimer synthons "
ABSTRACT
Methylphosphonate (MP) oligodeoxynucleotides (MPOs) are metabolically stable analogs of conventional DNA containing a methyl group in place of one of the non-bonding phosphoryl oxygens. All 16 possible chiral R P MP dinucleotides were synthesized and derivatized for automated oligonucleotide synthesis. These dimer synthons can be used to prepare (i) all-MP linked oligonucleotides having defined R P chirality at every other position (R P chirally enriched MPOs) or (ii) alternating R P MP/phosphodiester backbone oligonucleotides, depending on the composition of the 3 ' -coupling group. Chirally pure dimer synthons were also prepared with 2 ' - O -methyl sugar modifications. Oligonucleotides prepared with these R P chiral methylphosphonate linkage synthons bind RNA with significantly higher affinity than racemic MPOs.
..."Unlike natural phosphodiester oligonucleotides, MPOs contain chiral linkages. The conventional methods for synthesizing MPOs are not capable of forming methylphosphonate bonds without P epimerization. A typical racemic 18mer MPO contains 131 072 (2 17 ) different diastereomers."............
some terms:
Chirally pure dimer synthons Methylphosphonate oligodeoxynucleotides diastereomers P epimerization
skyship
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