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Titolo:
Effect of chemical modifications of cytosine and guanine in a CpG-Motif ofoligonucleotides: Structure-immunostimulatory activity relationships
Autore:
Kandimalla, ER; Yu, D; Zhao, QY; Agrawal, S;
Indirizzi:
Hybridon Inc, Cambridge, MA 02139 USA Hybridon Inc Cambridge MA USA 02139Hybridon Inc, Cambridge, MA 02139 USA
Titolo Testata:
BIOORGANIC & MEDICINAL CHEMISTRY
fascicolo: 3, volume: 9, anno: 2001,
pagine: 807 - 813
SICI:
0968-0896(200103)9:3<807:EOCMOC>2.0.ZU;2-G
Fonte:
ISI
Lingua:
ENG
Soggetto:
BACTERIAL-DNA; PHOSPHOROTHIOATE OLIGODEOXYNUCLEOTIDE; INTERLEUKIN-12; RESPONSES; INDUCTION; SEQUENCE; MICE;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
22
Recensione:
Indirizzi per estratti:
Indirizzo: Agrawal, S Hybridon Inc, 345 Vassar St, Cambridge, MA 02139 USA Hybridon Inc 345 Vassar St Cambridge MA USA 02139 MA 02139 USA
Citazione:
E.R. Kandimalla et al., "Effect of chemical modifications of cytosine and guanine in a CpG-Motif ofoligonucleotides: Structure-immunostimulatory activity relationships", BIO MED CH, 9(3), 2001, pp. 807-813

Abstract

Oligodeoxynucleotides containing unmethylated CpG-motifs stimulate the innate immune system, including inducing B-cell proliferation and cytokine production. However, the mechanism of immunostimulation by CpG-oligonucleotides and the precise structural requirements and specific functional groups ofcytosine and guanine necessary for recognition of and interaction with protein/receptor factors that are responsible for immune stimulation have not been elucidated. We sought to understand the critical role of each functional group of the cytosine and guanine moieties in a CpG-motif in inducing immunostimulatory activity. To this end, we examined structure-immunostimulatory activity relationships of phosphorothio ate oligodeoxynucleotides (PS-oligos) containing YpG- and CpR-motifs (Y and R stand for pyrimidine and purine analogues, respectively). The PS-oligos containing a YpG- motif in which the natural deoxycytidine was replaced with deoxy-5-hydroxycytidine or deoxy-N4-ethylcytidine showed immunostimulatory activity. Substitution of deoxycytidine with a deoxy-5-methylisocytidine, deoxyuridine, or deoxy-P-base-nucleoside in the YpG-motif completely abolished the immune stimulatory activity, similar to the results observed with deoxy-5-methylcytidine. In the case of PS-oligos containing a CpR-motif, 7-deazaguanine substitution for natural guanine showed immunostimulatory activity similar to that of a parent PS-oligo. These studies suggest that the 2-keto, 3-imino and 4-amino groups of cytosine, and the 1-imino, 2-amino and 6-keto groups of guanine in a CpG-motif are important for the immunostimulatory activity of CpG-PS-oligos. The absence of N7 on guanine of the CpG-motif does not affect immunostimulatory activity significantly. These studies suggest that it is possible todevelop YpG- and CpR-motifs as an alternative to CpG-motifs in PS-oligos for immunostimulatory studies. (C) 2001 Published by Elsevier Science Ltd. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 09/04/20 alle ore 20:14:25