Solid phase synthesis and RNA-binding activity of an arginine-containing nucleopeptide † †Electronic supplementary information (ESI) available. See DOI:  10.1039/c5ra25809j 
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Abstract

Here we report the solid phase synthesis and characterization (LC-ESIMS, CD) of a cationic nucleobase-containing α-peptide, composed of both l-arginine residues and l-lysine-based nucleoamino acids sequentially present in the structure. The binding properties of this novel basic nucleopeptide towards nucleic acids were investigated by CD spectroscopy which revealed the ability of the thymine-containing oligomer to bind both adenine-containing DNA (dA ₁₂) and RNA (poly rA) molecules inducing high conformational variations in the nucleic acid structures. Moreover, the artificial oligonucleotide inhibited the enzymatic activity of HIV reverse transcriptase, opening the door to the exploitation of novel antiviral strategies inspired to this molecular tool.

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Serum Stabilities of Short Tryptophan- and Arginine-Rich Antimicrobial Peptide Analogs

Leonard T. Nguyen, Johnny Chau, Nicole A. Perry … (2010)

Background Several short antimicrobial peptides that are rich in tryptophan and arginine residues were designed with a series of simple modifications such as end capping and cyclization. The two sets of hexapeptides are based on the Trp- and Arg-rich primary sequences from the “antimicrobial centre” of bovine lactoferricin as well as an antimicrobial sequence obtained through the screening of a hexapeptide combinatorial library. Methodology/Principal Findings HPLC, mass spectrometry and antimicrobial assays were carried out to explore the consequences of the modifications on the serum stability and microbicidal activity of the peptides. The results show that C-terminal amidation increases the antimicrobial activity but that it makes little difference to its proteolytic degradation in human serum. On the other hand, N-terminal acetylation decreases the peptide activities but significantly increases their protease resistance. Peptide cyclization of the hexameric peptides was found to be highly effective for both serum stability and antimicrobial activity. However the two cyclization strategies employed have different effects, with disulfide cyclization resulting in more active peptides while backbone cyclization results in more proteolytically stable peptides. However, the benefit of backbone cyclization did not extend to longer 11-mer peptides derived from the same region of lactoferricin. Mass spectrometry data support the serum stability assay results and allowed us to determine preferred proteolysis sites in the peptides. Furthermore, isothermal titration calorimetry experiments showed that the peptides all had weak interactions with albumin, the most abundant protein in human serum. Conclusions/Significance Taken together, the results provide insight into the behavior of the peptides in human serum and will therefore aid in advancing antimicrobial peptide design towards systemic applications.

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Identification and functional characterization of neo-poly(A) polymerase, an RNA processing enzyme overexpressed in human tumors.

Suzanne Topalian, Nell G Bond, Natalia Gonzales … (2001)

Poly(A) polymerase (PAP) plays an essential role in polyadenylation of mRNA precursors, and it has long been thought that mammalian cells contain only a single PAP gene. We describe here the unexpected existence of a human PAP, which we call neo-PAP, encoded by a previously uncharacterized gene. cDNA was isolated from a tumor-derived cDNA library encoding an 82.8-kDa protein bearing 71% overall similarity to human PAP. Strikingly, the organization of the two PAP genes is nearly identical, indicating that they arose from a common ancestor. Neo-PAP and PAP were indistinguishable in in vitro assays of both specific and nonspecific polyadenylation and also endonucleolytic cleavage. Neo-PAP produced by transfection was exclusively nuclear, as demonstrated by immunofluorescence microscopy. However, notable sequence divergence between the C-terminal domains of neo-PAP and PAP suggested that the two enzymes might be differentially regulated. While PAP is phosphorylated throughout the cell cycle and hyperphosphorylated during M phase, neo-PAP did not show evidence of phosphorylation on Western blot analysis, which was unexpected in the context of a conserved cyclin recognition motif and multiple potential cyclin-dependent kinase (cdk) phosphorylation sites. Intriguingly, Northern blot analysis demonstrated that each PAP displayed distinct mRNA splice variants, and both PAP mRNAs were significantly overexpressed in human cancer cells compared to expression in normal or virally transformed cells. Neo-PAP may therefore be an important RNA processing enzyme that is regulated by a mechanism distinct from that utilized by PAP.

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G-Quadruplex Forming Oligonucleotides as Anti-HIV Agents

Domenica Musumeci, Claudia Riccardi, Daniela Montesarchio (2015)

Though a variety of different non-canonical nucleic acids conformations have been recognized, G-quadruplex structures are probably the structural motifs most commonly found within known oligonucleotide-based aptamers. This could be ascribed to several factors, as their large conformational diversity, marked responsiveness of their folding/unfolding processes to external stimuli, high structural compactness and chemo-enzymatic and thermodynamic stability. A number of G-quadruplex-forming oligonucleotides having relevant in vitro anti-HIV activity have been discovered in the last two decades through either SELEX or rational design approaches. Improved aptamers have been obtained by chemical modifications of natural oligonucleotides, as terminal conjugations with large hydrophobic groups, replacement of phosphodiester linkages with phosphorothioate bonds or other surrogates, insertion of base-modified monomers, etc. In turn, detailed structural studies have elucidated the peculiar architectures adopted by many G-quadruplex-based aptamers and provided insight into their mechanism of action. An overview of the state-of-the-art knowledge of the relevance of putative G-quadruplex forming sequences within the viral genome and of the most studied G-quadruplex-forming aptamers, selectively targeting HIV proteins, is here presented.

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Journal

Journal ID (nlm-ta): RSC Adv

Journal ID (iso-abbrev): RSC Adv

Title: Rsc Advances

Publisher: Royal Society of Chemistry

ISSN (Electronic): 2046-2069

Publication date (Print): 02 February 2016

Publication date (Electronic): 26 January 2016

Volume: 6

Issue: 17

Pages: 14140-14148

Affiliations

[a ] CNR , Istituto di Biostrutture e Bioimmagini – (Mezzacannone site and Headquarters) , 80134 Napoli , Italy . Email: giovanni.roviello@ 123456cnr.it ; Fax: +39-081-2534574 ; Tel: +39-081-2534585

[b ] Università di Napoli “Federico II” , Dipartimento di Farmacia , 80134 Napoli , Italy

[c ] Università di Napoli “Federico II” , Dipartimento di Scienze Chimiche , 80126 Napoli , Italy

[d ] Università di Napoli “Federico II” , Dipartimento di Ingegneria Chimica , dei Materiali e della Produzione Industriale (DICMaPI) , 80125 Napoli , Italy

Article

Publisher ID: c5ra25809j

DOI: 10.1039/c5ra25809j

PMC ID: 5635565

PubMed ID: 29057071

SO-VID: 9b4b83d0-443a-46aa-8a06-6b3c85dad512

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This is an Open Access article distributed under the terms of the Creative Commons Attribution-NonCommercial 3.0 Unported License ( http://creativecommons.org/licenses/by-nc/3.0/) which permits unrestricted non-commercial use, distribution, and reproduction in any medium, provided the original work is properly cited.

History

Date received : 3 December 2015

Date accepted : 15 January 2016

Notes

†Electronic supplementary information (ESI) available. See DOI: 10.1039/c5ra25809j

Data availability:

Solid phase synthesis and RNA-binding activity of an arginine-containing nucleopeptide†

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Most cited references 36

Serum Stabilities of Short Tryptophan- and Arginine-Rich Antimicrobial Peptide Analogs

Identification and functional characterization of neo-poly(A) polymerase, an RNA processing enzyme overexpressed in human tumors.

G-Quadruplex Forming Oligonucleotides as Anti-HIV Agents

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