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Modified Analogues (modified + analogue)
Selected AbstractsSynthesis and In-vitro Activity of 4,-Modified Analogues of ddA as Potent Anti-HIV AgentsARCHIV DER PHARMAZIE, Issue 10 2009Joon Hee Hong Abstract This paper reports the synthesis of novel 4,-hydrophobic pocket deoxythreosyl C-nucleosides. The key threose-like intermediates 9 and 14 were constructed from acyclic ketone derivatives, respectively. The antiviral activities of the synthesized compounds against the HIV-1, HSV-1, HSV-2, and HCMV viruses were evaluated. The 9-deaza-adenine derivatives 10 and 20 showed good anti-HIV activity without exhibiting significant cytotoxicity. [source] Differential Extracellular Signal-Regulated Kinases 1 and 2 Activation by the Angiotensin Type 1 Receptor Supports Distinct Phenotypes of Cardiac MyocytesBASIC AND CLINICAL PHARMACOLOGY & TOXICOLOGY, Issue 5 2007Mark Aplin The biological importance of this, however, remains obscure. Application of the modified analogue [Sar1, Ile4, Ile8]-AngII ([SII] AngII) allowed us to dissect the two pathways of ERK1/2 activation in native cardiac myocytes. Although cytosol-retained, the ,-arrestin2-bound pool of ERK1/2 represents an active signalling component that phosphorylates p90 Ribosomal S6 Kinase, a ubiquitous and versatile mediator of ERK1/2 signal transduction. Moreover, the ,-arrestin2-dependent ERK1/2 signal supports intact proliferation of cardiac myocytes. In contrast to Gq -activated ERK1/2, and in keeping with its failure to translocate to the nucleus, the ,-arrestin2-scaffolded pool of ERK1/2 does not phosphorylate the transcription factor Elk-1, induces no increased transcription of the immediate-early gene c-Fos, and does not entail myocyte hypertrophy. These results clearly demonstrate the biological significance of differential signalling by the AT1R. The opportunity to separate desirable cardiac myocyte division from detrimental hypertrophy holds promise that novel pharmacological approaches will allow targeting of pathway-specific actions. [source] Surface-enhanced Raman difference between bombesin and its modified analogues on the colloidal and electrochemically roughen silver surfacesBIOPOLYMERS, Issue 10 2008Edyta Podstawka Abstract In this article, surface-enhanced Raman scattering (SERS) spectra of bombesin (BN) and its six modified analogues ([D-Phe12]BN, [Tyr4]BN, [Tyr4,D-Phe12]BN, [D-Phe12,Leu14]BN, [Leu13 -®-Leu14]BN, and [Lys3]BN) on a colloidal silver surface are reported and compared with SERS spectra of these species immobilized onto an ellectrochemically roughen silver electrode. Changes in enhancement and wavenumber of proper bands upon adsorption on different silver surfaces are consistent with BN and its analogues adsorption primarily through Trp8. Slightly different adsorption states of these molecules are observed depending upon natural amino acids substitution. For example, the indole ring in all the peptides interacts with silver nanoparticles in a edge-on orientation. It is additionally coordinated to the silver through the N1H bond for all the peptides, except [Phe12]BN. This is in contrary to the results obtained for the silver roughen electrode that show direct but not strong N1H/Ag interaction for all peptides except [D-Phe12,Leu14]BN and [Leu13 -®-Leu14]BN. For BN only CO is not involved in the chemical coordination with the colloidal surface. [Lys3]BN and BN also adsorb with the CN bond of NH2 group normal and horizontal, respectively, to the colloidal surface, whereas CNH2 in other peptides is tilted to this surface. Also, the Trp8 CH2 moiety of only [Tyr4]BN, [Lys3]BN, and [Tyr4,D-Phe12]BN coordinates to Ag, whereas the Phe12 ring of [Phe12]BN, [Tyr4,D-Phe12]BN, and [D-Phe12,Leu14]BN assists in the peptides binding only on the colloidal silver. © 2008 Wiley Periodicals, Inc. Biopolymers 89: 807,819, 2008. This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com [source] Investigation of molecular structure of bombesin and its modified analogues nonadsorbed and adsorbed on electrochemically roughened silver surfaceBIOPOLYMERS, Issue 6 2008Edyta Podstawka Abstract This work describes the molecular structure of bombesin (BN) and its analogs on the basis of the absorption infrared and Raman results described below. In these analogues is replaced one ([D-Phe12]BN, [Tyr4]BN, and [Lys3]BN) or two ([Tyr4,D-Phe12]BN, [D-Phe12,Leu14]BN, and [Leu13 -®-Leu14]BN) amino acid residues within the peptide chain with a synthetic amino acid, creating antagonists to bombesin, which are useful in the treatment of cancer. It is also used surface enhanced Raman scattering (SERS) to study the differences and changes in the vibrational spectra of BN and its analogs, which were attached to an electrochemically roughened silver surface as these peptides interacted with target proteins. This work explores the use of SERS for molecules anchored to a macroscopic silver surface to interrogate the interaction of these peptides with protein receptors. The results presented here show that all peptides coordinate to the macroscopic silver surface through an indole ring and the methylene group of Trp8, the CO fragment, and an amide bond; however, the orientation of these fragments on the electrochemically roughened silver surface and the strength of the interactions with this surface is slightly different for each peptide. For example, the interaction of CH2 of [D-Phe12]BN, [Tyr4,D-Phe12]BN, [D-Phe12,Leu14]BN, [Leu13 -®-Leu14]BN, and [Lys3]BN with the silver surface perturbed the vertical orientation of the Trp8 indole ring on this surface. Hence, the indole ring adopted a close to perpendicular orientation on the silver surface for BN and [Tyr4]BN, only. © 2007 Wiley Periodicals, Inc. Biopolymers 89: 506,521, 2008. This article was originally published online as an accepted preprint. The "Published Online" date corresponds to the preprint version. You can request a copy of the preprint by emailing the Biopolymers editorial office at biopolymers@wiley.com [source] 3-Hydroxybenzene 1,2,4-Trisphosphate, a Novel Second Messenger Mimic and unusual Substrate for Type-I myo -Inositol 1,4,5-Trisphosphate 5-Phosphatase: Synthesis and PhysicochemistryCHEMBIOCHEM, Issue 11 2006Stephen J. Mills Dr. Abstract 3-Hydroxybenzene 1,2,4-trisphosphate 4 is a new myo -inositol 1,4,5-trisphosphate analogue based on the core structure of benzene 1,2,4-trisphosphate 2 with an additional hydroxyl group at position-3, and is the first noninositol based compound to be a substrate for inositol 1,4,5-trisphosphate 5-phosphatase. In physicochemical studies on 2, when three equivalents of protons were added, the 31P NMR spectrum displayed monophasic behaviour in which phosphate-1 and phosphate-2 behaved independently in most of the studied pH range. For compound 4, phosphate-2 and phosphate-4 interacted with the 3-OH group, which does not titrate at physiological pH, displaying complex biphasic behaviour which demonstrated co-operativity between these groups. Phosphate-1 and phosphate-2 strongly interacted with each other and phosphate-4 experienced repulsion because of the interaction of the 3-OH group. Benzene 1,2,4-trisphosphate 2 is resistant to inositol 1,4,5-trisphosphate type I 5-phosphatase catalysed dephosphorylation. However, surprisingly, 3-hydroxybenzene 1,2,4-trisphosphate 4 was dephosphorylated by this 5-phosphatase to give the symmetrical 2,3-dihydroxybenzene 1,4-bisphosphate 16. The extra hydroxyl group is shown to form a hydrogen bond with the vicinal phosphate groups at ,15,°C, and 1H NMR titration of the ring and hydroxyl protons in 4 shows the OH proton to be strongly stabilized as soon as the phosphate groups are deprotonated. The effect of the phenolic 3-OH group in compound 4 confirms a critical role for the 6-OH group of the natural messenger in the dephosphorylation mechanism that persists even in radically modified analogues. [source] Highly Fluorescent Conjugated Pyrenes in Nucleic Acid Probes: (Phenylethynyl)pyrenecarbonyl-Functionalized Locked Nucleic AcidsCHEMISTRY - A EUROPEAN JOURNAL, Issue 35 2008Irina Abstract In recent years, fluorescently labeled oligonucleotides have become a widely used tool in diagnostics, DNA sequencing, and nanotechnology. The recently developed (phenylethynyl)pyrenes are attractive dyes for nucleic acid labeling, with the advantages of long-wave emission relative to the parent pyrene, high fluorescence quantum yields, and the ability to form excimers. Herein, the synthesis of six (phenylethynyl)pyrene-functionalized locked nucleic acid (LNA) monomers M1,M6 and their incorporation into DNA oligomers is described. Multilabeled duplexes display higher thermal stabilities than singly modified analogues. An increase in the number of phenylethynyl substituents attached to the pyrene results in decreased binding affinity towards complementary DNA and RNA and remarkable bathochromic shifts of absorption/emission maxima relative to the parent pyrene fluorochrome. This bathochromic shift leads to the bright fluorescence colors of the probes, which differ drastically from the blue emission of unsubstituted pyrene. The formation of intra- and interstrand excimers was observed for duplexes that have monomers M1,M6 in both complementary strands and in numerous single-stranded probes. If more phenylethynyl groups are inserted, the detected excimer signals become more intense. In addition, (phenylethynyl)pyrenecarbonyl,LNA monomers M4, M5, and M6 proved highly useful for the detection of single mismatches in DNA/RNA targets. [source] | ||||||||||