Peptide Ribonucleic Acid Research Articles

Peptide Ribonucleic Acid (PRNA)–Arginine Hybrids. Effects of Arginine Residues Alternatingly Introduced to PRNA Backbone on Aggregation, Cellular Uptake, and Cytotoxicity

Intracellular delivery is crucial not only in achieving effective oligonucleotide therapeutics but also for a wide variety of therapeutic strategies. In this study to elucidate the effects of the number of incorporated arginine residues on cell membrane permeability, we designed a series of peptide ribonucleic acids (PRNAs) that alternatingly incorporated 4, 8, or 12 arginine residues (PRR1-3) in the PRNA backbone for experimental verifications. Indeed, the cellular uptake efficiency and the aggregation properties turned out to be critical functions of the number of incorporated arginine residues. Thus, the optimized PRR2 that incorporates 8 arginines showed the most efficient cellular uptake ability, much higher than that of octaarginine, without accompanying cytotoxicity or aggregation.

Module Strategy for Peptide Ribonucleic Acid (PRNA)–DNA and PRNA–Peptide Nucleic Acid (PNA)–DNA Chimeras: Synthesis and Interaction of Chimeras with DNA and RNA

Employing the module strategy based on our recent finding that the recognition behavior of peptide ribonucleic acid (PRNA) with complementary DNA/RNA is effectively controlled by the anti-to-syn or...

Synthesis and DNA-recognition behavior of a novel peptide ribonucleic acid with a serine backbone (oxa-PRNA)

(2 S)-2-Fmoc-amino-3-(5′-deoxyuridinylamino)-3-oxopropyloxyacetic acid was synthesized from l-serine as a monomer for preparing the second-generation peptide ribonucleic acid with an oxa-peptide backbone (oxa-PRNA). The ether linkage was incorporated to improve the modest solubility in aqueous solution of the original PRNA with an iso-glutamine backbone, without harming the ability of the amino-uridine side chain to switch the anti/ syn nucleobase orientation by adding borax. Indeed, CD spectral examinations revealed that the Fmoc-protected oxa-PRNA uridine monomer (Fmoc-oxa-PRNA(U)), synthesized in three steps, switched the nucleobase orientation from anti to syn in phosphate buffer upon addition of borax. Homo-12mers of oxa-PRNA(U) with and without Arg end caps were prepared in moderate yields by the Fmoc solid-phase synthesis. Both of the N- and C-terminus-capped oxa-PRNA(U) 12mers thus synthesized were shown to hybridize with the complementary DNA 12mer (d(A 12)) with stabilities comparable to that observed for the natural pair.

Studies on the effects of arginine residues introduced to peptide ribonucleic acids (PRNA) on the complex stability with RNA

In this study, a series of novel alpha-Peptide ribonucleic acid (alpha-PRNA) oligomers, possessing alternative alpha-PRNA/arginine or serine sequences, were newly designed, synthesized, and evaluated as the third-generation PRNA. As expected, these alpha-PRNAs formed highly stable sequence-specific complexes with the complementary RNAs, for which both the conventional hydrogen-bonding interactions between the complementary nucleobase pairs and the electrostatic interactions between the arginine's guanidinium cation and the RNA's phosphate anion on the backbone are jointly responsible. Moreover, in the cases of alpha-PRNA and single point mismatched DNA mixing systems, appreciable T(m) could not be observed, thus alpha-PRNAs containing Arg were expected to have high nucleobase sequence discrimination abilities. It was demonstrated that the recognition behavior of alpha-PRNA with Arg/Ser backbone with complementary RNA can be controlled externally through the orientation change of pyrimidine nucleobase induced by borate ester formation of the ribose's 2',3'-cis-diol.

Effects of Arginine Residue Introduction upon Interaction and Complexation Behavior of Peptide Ribonucleic Acids (PRNAs) with RNA: Synthesis and Properties of -Containing Arginine

A novel nucleic acid model using alpha-peptide ribonucleic acid (alpha-PRNA) possessing alternative alpha-PRNA/arginine sequences, where the arginine residue would be expected to stabilize the complex not only by the conventional hydrogen-bonding interactions between the complementary nucleobase pairs but also through the electrostatic interactions between positively charged side-chain groups and RNA's phosphate anions on the backbone. These alpha-PRNA form stable sequence-specific complex with the complementary RNA.

Synthesis of Peptide Ribonucleic Acid (PRNA)-DNA Chimera and Interaction with DNA and RNA

Recently, we have demonstrated that effective control of the recognition behavior of peptide ribonucleic acid (PRNA) with complementary DNA is possible through the anti-to-synorientational change of pyrimidine nucleobase induced by borate ester formation. In this study, DNA-PRNA chimera was prepared by the solidphase synthesis. In the DNA-PRNA chimeras, both PRNA and DNA domains work as recognition sites for the complementary DNA/RNAs to form stable complex, while DNA-RNA hybrids formed in the DNA domains of DNA-PRNA chimera should be substrates to the hydrolysis by RNase H and PRNA moieties work as recognition control/switching devices and as inhibitor for the hydrolysis by exonucleases. Interaction of the DNA-PRNA chimera with DNA and RNA has been discussed.

DNA Recognition and Recognition Control of α-Peptide Ribonucleic Acids by External Factors

Peptide ribonucleic acid (PRNA) is one of artificial nucleic acids, which enables us to control its nucleobase orientation and recognition behavior by external factors through the synergetic effects of reversible borate ester formation and intramolecular hydrogen bond formation. In this study, a series of novel alpha-PRNA oligomers, possessing alternative alpha-PRNA/basic amino acid sequences, were newly designed, synthesized, and evaluated as the second-generation PRNA. As expected, these alpha-PRNAs indeed formed highly stable sequence-specific complexes with the complementary DNAs, for which both the conventional hydrogen-bonding interactions between the complementary nucleobase pairs and the electrostatic interactions between the basic amino acid's ammonium cation and the DNA's phosphate anion on the backbone are jointly responsible.

Functionalization of PNA — Novel Strategy for Active Control of DNA Recognition by External Factors Using Peptide Ribonucleic Acids (PRNA)

AbstractFor Abstract see ChemInform Abstract in Full Text.

Functional Artificial Nucleic Acids: Peptide Ribonucleic Acids (Prnas) - Novel Strategy for Active Control of DNA Recognition by External Factors

Functional Artificial Nucleic Acids: Peptide Ribonucleic Acids (Prnas) - Novel Strategy for Active Control of DNA Recognition by External Factors

Synthesis of peptide ribonucleic acid consisting of D- and L- -glutamic acid as a backbone structure

A novel nucleic acid model using peptide ribonucleic acid (PRNA), which contains 5-amino-5-deoxyribonucleoside as a recognition site for nucleic acids and consists D-glutamic acid (D-PRNA) instead of L-glutamic acid (L-PRNA) as a backbone structure, has been designed and synthesized. Difference between D-PRNA and L-PRNA oligomers was elucidated on the basis of the effects of chirality of gamma-glutamic acid backbone upon structure elucidated by CD spectra.

Synthesis and Conformation Control of Peptide Ribonucleic Acid (PRNA) Containing 5′-Amino-5′-deoxyribopyrimidine and 5′-Amino-5′-deoxyribopurinenucleosides

A novel nucleic acid model, a peptide ribonucleic acid (PRNA) tethering 5′-amino-5′-deoxypyrimidine ribonucleoside as a recognition site for nucleic acids, was designed and synthesized. It was demonstrated that the recognition behavior of PRNA could be controlled externally through switching the orientation of the pyrimidine nucleobase of PRNA induced by added borates. We extended this methodology of controlling the nucleobase orientation and recognition behavior of novel mono- and oligomeric PRNAs containing not only 5′-amino-5′-deoxypyrimidinenucleosides but also 5′-amino-5′-deoxypurinenucleosides. In the case of PRNA oligomer containing pyrimidine-purine mixed sequence, efficient orientation switching of nucleobases induced by added borates was also observed.

External reversible control of recognition behavior of alpha-peptide ribonucleic acid (alpha-PRNA) through anti-syn orientational switching of the nucleobase induced by borate esterification of the cis-2',3'-diol.

A novel nucleic acid model using peptide ribonucleic acid (PRNA), which contains 5'-amino-5'-deoxypyrimidine ribonucleoside as a recognition site for nucleic acids, has been designed, synthesized and applied to the external reversible control of recognition behavior of the complementary polynucleotide through the orientational switching of the nucleobase induced by borate.

A novel strategy for reversible control of conformation and DNA/RNA recognition of peptide ribonucleic acid (PRNA) by external factors.

A novel nucleic acid model using peptide ribonucleic acid (PRNA), which contains 5'-amino-5'-deoxyribonucleoside as a recognition site for nucleic acids, has been designed, synthesized and applied to the external reversible control of recognition behavior of the complementary oligomeric DNA through the orientational switching of the nucleobase induced by borates. In case of PRNA 12-mers, efficient orientational change of nucleobases was observed. Furthermore, these oligomeric PRNAs form a stable complex with complementary DNA's and the recognition behavior of oligomeric PRNAs with DNA's is controlled by the borate added as an external factor.

Solid-phase synthesis of peptide ribonucleic acids (PRNA)

The range of available peptide ribonucleic acid (PRNA) monomers was fully expanded for the use in solid-phase synthesis of PRNA oligomers, which were designed to reversibly control the recognition and complexation behavior of the complementary DNA/RNA by external factors. A couple of PRNA 12-mers with desired purine–pyrimidine mixed sequences were prepared indeed in high yields by the solid-phase synthesis.

DNA recognition control of gamma-PRNA and mismatched base effects upon complex stability.

Oligomeric peptide ribonucleic acids (PRNA's), tethering 5'-amino-5'-deoxyribonucleosides as a recognition site for nucleic acids, has been designed and synthesized by solid phase method. PRNA 12-mer found to form stable duplex with complementary DNA.PRNA.DNA duplex composed of PRNA with mismatched DNA has 10-degree lower melting temperature than fullmatched PRNA.DNA duplex. These results demonstrate that binding of PRNA with DNA is sequence specific. It should be emphasized that the on-off switching of PRNA.DNA duplex formation has been realized by the borate added as an external factor.

Conformation and recognition control of peptide ribonucleic acid containing pyrimidine/purine mixed sequence.

Peptide ribonucleic acids (PRNA), tethering 5'-amino-5'-deoxyribonucleoside as a recognition moiety for RNA/DNA, have been designed and synthesized, as a novel nucleic acid model. External switching of the recognition behavior of PRNA containing not only pyrimidine nucleobase but also purine nucleobase, with complementary oligomeric DNA/RNA has been demonstrated for the first time through both the orientational switching of the nucleobase of PRNA and electrostatic repulsion between borate ester anion of PRNA and phosphodiester anion of DNA/RNA, induced by added borates.

Synthesis and conformation control of peptide ribonucleic acid containing 5'-amino-5'-deoxyribopurinenucleosides.

A novel nucleic acid model, i.e. peptide ribonucleic acid (PRNA), tethering 5'-amino-5'-deoxypyrimidine ribonucleoside as a recognition site for nucleic acids, has been designed and synthesized. We have demonstrated that the recognition behavior of PRNA with complementary oligopurinenucleotides can be controlled externally through the orientational switching of the pyrimidine nucleobase of PRNA induced by added borates. We extend this methodology of controlling the nucleobase orientation and recognition behavior of novel mono and oligomeric PRNAs containing 5'-amino-5'-deoxypyrimidine and/or purinenucleosides. In case of the PRNA oligomer containing pyrimidine-purine mixed sequence, efficient orientational switching of nucleobases induced by added borates was also observed.

Peptide Ribonucleic Acids (PRNA). 2. A Novel Strategy for Active Control of DNA Recognition through Borate Ester Formation

The effect of adding borax and boric acids on the nucleobase orientation and recognition behavior of novel mono- and oligomeric peptide ribonucleic acids (PRNAs) has been investigated. The base orientation of 5‘-amino-5‘-deoxyuridine and 5‘-amino-5‘-deoxycytidine was shown by CD and NOE difference spectral studies to switch from anti to syn in borate buffer or upon addition of borax. The origin of this phenomenon is elucidated to be the cooperative effect of the cyclic borate esterification of the sugar's cis-2‘,3‘-diol and the hydrogen-bonding interaction between the sugar's 5‘-amino proton and the base's 2-carbonyl oxygen. Because this new strategy for switching the base orientation through the addition of borate is potentially applicable to the recognition control of nucleic acids if the sugar's 5‘-proton and cis-2‘,3‘-diol remain unmodified, we synthesized a series of PRNAs, in which the 5‘-amino-5‘-deoxypyrimidine ribonucleoside moiety was appended to a mono- or oligo(γ-l-glutamic acid) backbone thro...

Expression of gastrin-releasing peptide (GRP) and GRP receptors in the pregnant human uterus at term.

Synthesis of both gastrin-releasing peptide (GRP) and messenger ribonucleic acid (mRNA) has been demonstrated in pregnant sheep, but studies in women have not been reported. Therefore, we examined the uterus and placenta of pregnant women at term for synthesis of GRP and expression of GRP receptor genes BRS-3 and GRP-R. A transcript of 0.95 kilobases, corresponding to GRP mRNA, was detected in endometrium and myometrium, but not in amnion, chorion, placenta, or nonpregnant endometrium. GRP immunoreactivity (GRP-ir) was detected in half (three of six) of the endometrial (1.23 +/- 0.04 pmol/g) and myometrial (0.73 +/- 0.04 pmol/g) samples and in some, but not all, samples of amnion (one of four subjects; 0.6 pmol/g), chorion (four of five subjects; 0.8 +/- 0.2 pmol/g), placenta (two of six subjects; 0.5 +/- 0.2 pmol/g), and amniotic fluid (four of six subjects; 59 +/- 19 fmol/mL). GRP-ir was present in the maternal circulation (44 +/- 12 fmol/mL) and was higher in plasma obtained from the umbilical artery (152 +/- 14 fmol/mL) and vein (143 +/- 24 fmol/mL). The major peak of GRP-ir in pregnant endometrial tissue was larger than GRP-(1-27), as determined by gel filtration chromatography. Minor peaks were also observed: two larger than the main form and one corresponding to GRP-(18-27). mRNA for GRP receptors GRP-R and BRS-3 was detected by semiquantitative reverse transcription-PCR. For both receptors, mRNA was higher in the pregnant endometrium than in the nonpregnant endometrium but was detected in all of the uteroplacental tissues examined. GRP-R mRNA predominated in the pregnant endometrium, whereas BRS-3 mRNA predominated in the membranes and placenta. In these tissues, PCR for BRS-3 mRNA gave rise to an additional product (approximately 50 bp larger). These studies demonstrated that a peptide larger than, but related to, GRP is synthesized in the pregnant human uterus and is secreted into the maternal and fetal circulations. The detection of mRNA for GRP-R, BRS-3, and possibly a transcript variant of BRS-3 as well as the detection of a peptide larger than, but related to, GRP suggest a novel regulatory unit in the human reproductive tract.

Glucocorticoids regulate somatostatin peptide and steady state messenger ribonucleic acid levels in normal rat tissues and in a somatostatin-producing islet tumor cell line (1027B2)

Glucocorticoids regulate somatostatin peptide and steady state messenger ribonucleic acid levels in normal rat tissues and in a somatostatin-producing islet tumor cell line (1027B2)