Receptors nucleic acids

Manimala JC, Wiskur SL, Ellington AD, Anslyn EV. Tuning the specificity of a synthetic receptor using a selected nucleic acid receptor. Journal of the American Chemical Society 2004, 126, 16515-16519. 

An example will be reported here, based on nucleic acid receptors called aptamers, selected in vitro, which can be produced for a wide range of molecules [11] and represent now one of the frontiers of nucleic acid-based sensing. 

Sequence of electrostatic contour maps through the intercalation plane of the nucleic acid receptor in mediating the receipt of ethidium bromide. Modified from ref. 41 (bottom). 

From a structural point of view, the nucleic acid receptor folds upon small molecule binding from a more or less disordered structure into a well-defined binding pocket, encapsulating the target. Numerous studies have shown that such structural reorganization of the functional nucleic acid, mediated by the small... 

Melatonin [73-31-4] C 2H N202 (31) has marked effects on circadian rhythm (11). Novel ligands for melatonin receptors such as (32) (12), C2yH2gN202, have affinities in the range of 10 Af, and have potential use as therapeutic agents in the treatment of the sleep disorders associated with jet lag. Such agents may also be usehil in the treatment of seasonal affective disorder (SAD), the depression associated with the winter months. Histamine (see Histamine and histamine antagonists), adenosine (see Nucleic acids), and neuropeptides such as corticotropin-like intermediate lobe peptide (CLIP) and vasoactive intestinal polypeptide (VIP) have also been reported to have sedative—hypnotic activities (7). 

The development of nucleic acid-based therapeutics is not as straightforward as researchers had initially anticipated. Stability, toxicity, specificity, and delivery of the compounds continue to be challenging issues that need further optimization. In recent years, researchers have come up with intricate solutions that have greatly improved the efficacy of potential antisense, ribozyme, as well as RNAi-based therapeutics. Clinical trials for all these types of nucleic acid-based therapeutics are underway. So far, data from several trials and studies in animal models look promising, in particular, the therapies that trigger the RNAi pathway. However, history has shown that compounds that do well in phase I or phase II clinical trials may still fail in phase III. A striking example is the nonspecific suppression of angiogenesis by siRNA via toII-Iike receptor 3 (Kleinman et al. 2008). It will become clear in the near future which compounds will make it as a new class of antiviral therapeutics. 

Gambacorti-Passerini C., Mologni L, Bertazzoli C., le Coutre P., Marchesi E., Grignani F., Nielsen P.E. In vitro transcription and translation inhibition by anti-promyelocytic leukemia (PML)/re-tinoic acid receptor-alpha and anti-PML peptide nucleic acid. Blood 1996 88 1411-1417. 

Sun L., Fuselier J.A., Murphy W.A., Coy D.H. Antisense peptide nucleic acids conjugated to somatostatin analogs and targeted at the n-myc oncogene display enhanced cytotoxity to human neuroblastoma 1M.R.32 cells expressing somatostatin receptors. Peptides 2002 23 1557-1565. 

Mologni L., Marches E., Nielsen P.E., Gai4BACOrti-Passerini C. Inhibition of promyelocytic leukemia (PML)/retinoic acid receptor-alpha and PML expression in acute promyelocytic leukemia cells by anti-PML peptide nucleic acid. Cancer Res. 2001 61 5468-5473. 

Karras J.G., Maier M.A., Lu T, Watt A., Manoharan M. Peptide nucleic acids are potent modulators of endogenous pre-mRNA splicing of the murine inter-leukin-5 receptor-alpha chain. Biochemistry 2001 40 7853-7859. 

D. J., Douglas C. L, Boules M., Stewart J.A., Zhao L., Lacy B., Cusack B., Fauq A., Richelson E. Peptide nucleic acids targeted to the neurotensin receptor and administered i.p. cross the blood-brain barrier and specifically reduce gene expression. Proc. Natl Acad. Sci. USA 1999 96 7053-7058. 

A systematic nomenclature has been developed for the chemokine receptors (see Table 1). Thus, receptors for CC chemokines are referred to as CCR, receptors for CXC chemokines as CXCR, and the receptors for the XC and CX3C chemokines as XCR and CX3CR, respectively. To date, there are 10 CCRs (CCRs 1 to 10), 7 CXCRs, a single XCR, and a single CX3CR. The numbering is based on the date of deposition of the chemokine receptor sequence within the nucleic acid databases. For orphan receptors, this date refers to the point of identification of the orphan receptors as chemokine receptors and not to the date of initial deposition in the cDNA databases. 

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