RNA-binding and viral reverse transcriptase inhibitory activity of a novel cationic diamino acid-based peptide.

Istituto di Biostrutture e Bioimmagini-CNR, via Mezzocannone 16, I-80134 Napoli, Italy.
Journal of Medicinal Chemistry (Impact Factor: 5.48). 03/2011; 54(7):2095-101. DOI: 10.1021/jm1012769
Source: PubMed

ABSTRACT A novel cationic peptide based on L-lysine and L-diaminobutyric acid was prepared for the first time by solid phase synthesis. After HPLC purification and ESI MS characterization, we studied by CD and IR spectroscopy the structural features of the novel basic peptide, which is able to form a β-turn-like structure. Furthermore, its interaction with DNA and RNA was investigated by CD and UV spectroscopy, which revealed a preferential RNA-binding ability of the sequential peptide, whereas its inhibitory activity toward HIV and Moloney murine leukemia virus (MMLV) reverse transcriptase action was evaluated by semiquantitative PCR. The cationic sequential peptide was able to inhibit the reverse transcriptase activity in both cases, even if our PCR data suggested a major activity in the case of HIV-RT, probably due to the stronger cationic peptide-protein interaction evidenced by UV spectroscopy.

  • Source
    [Show abstract] [Hide abstract]
    ABSTRACT: In this Letter, we investigated the binding properties towards nucleic acids of a thymine-functionalized oligolysine, composed of nucleobase-bearing amino acid moieties and underivatized l-lysine residues alternate in the backbone. The basic nucleopeptide proved to be well soluble in water and able to interact with both DNA and RNA, as suggested by circular dichroism, UV and surface plasmon resonance studies performed on the thymine-containing oligomer with both adenine-containing DNA (dA12) and RNA (rA12 and poly rA) molecules. In both cases the thymine-functionalized oligolysine was proven to form complexes characterized by a 1:1 T/A stoichiometric ratio, as evidenced by CD titration. UV melting experiments revealed that the complex formed between the homothymine oligolysine and rA12 RNA was more stable than the complex with dA12 DNA probably due to the additional H-bonding of the 2'-OH groups in RNA, that reinforces the overall interaction with the nucleopeptide. Finally, human serum stability assays were conducted on the thymine-bearing nucleopeptide which showed a half-life of 45min.
    Bioorganic & medicinal chemistry 01/2014; · 2.82 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: ɛ-Polylysine (ɛ-PL) is a homopolyamide linked by the peptide bond between the carboxylic and epsilon amino group of adjacent lysine molecules. It is naturally occurring biodegradable and nontoxic towards human. This review article gives an insight about the various ɛ-PL producing strains, their screening procedures, mechanism of synthesis, characterization, and its application in the medical field. The poly cationic nature of ɛ-PL at physiological pH makes it as one of the potential candidates in the field of drug delivery. Most of the biomedical applications till date use synthetic α-PLL as a raw material. However, it is believed that naturally occurring ɛ-PL would be an ideal substitute.
    Biochemical Engineering Journal 11/2012; 65(june 2012):70-81. · 2.37 Impact Factor
  • [Show abstract] [Hide abstract]
    ABSTRACT: We report here an efficient one-pot method for the synthesis of α,β-differentiated diamino esters directly from cinnamate esters using N,N-dichloro-p-toluenesulfonamide and benzylamine as nitrogen sources. The key transformations include a Cu-catalyzed aminohalogenation and aziridination, followed by an intermolecular SN2 nucleophilic ring opening by benzylamine. The reactions feature a wide scope of substrates and proceed with excellent stereo- and regioselectivity (anti:syn >99:1) .
    Beilstein Journal of Organic Chemistry 01/2014; 10:1802-1807. · 2.80 Impact Factor


Available from
May 16, 2014