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Titolo:
Improved bioavailability to the brain of glycosylated Met-enkephalin analogs
Autore:
Egleton, RD; Mitchell, SA; Huber, JD; Janders, J; Stropova, D; Polt, R; Yamamura, HI; Hruby, VJ; Davis, TP;
Indirizzi:
Univ Arizona, Coll Med, Dept Pharmacol, Tucson, AZ 85724 USA Univ ArizonaTucson AZ USA 85724 ed, Dept Pharmacol, Tucson, AZ 85724 USA Univ Arizona, Dept Chem, Tucson, AZ 85724 USA Univ Arizona Tucson AZ USA 85724 Arizona, Dept Chem, Tucson, AZ 85724 USA
Titolo Testata:
BRAIN RESEARCH
fascicolo: 1, volume: 881, anno: 2000,
pagine: 37 - 46
SICI:
0006-8993(20001020)881:1<37:IBTTBO>2.0.ZU;2-4
Fonte:
ISI
Lingua:
ENG
Soggetto:
SOLID-PHASE SYNTHESIS; ALPHA-AMINOISOBUTYRIC-ACID; GUINEA-PIG BRAIN; BLOOD-BRAIN; BARRIER TRANSPORT; OPIOID-PEPTIDES; TRANSCYTOSIS; ENDOTHELIUM; RECEPTOR; PROTEIN;
Keywords:
bioavailability; antinociception; structure activity; peptide;
Tipo documento:
Article
Natura:
Periodico
Settore Disciplinare:
Life Sciences
Citazioni:
61
Recensione:
Indirizzi per estratti:
Indirizzo: Davis, TP Univ Arizona, Coll Med, Dept Pharmacol, 1501 N Campbell Ave,POB 245050, Tucson, AZ 85724 USA Univ Arizona 1501 N Campbell Ave,POB 245050 Tucson AZ USA 85724
Citazione:
R.D. Egleton et al., "Improved bioavailability to the brain of glycosylated Met-enkephalin analogs", BRAIN RES, 881(1), 2000, pp. 37-46

Abstract

The blood-brain barrier prevents the entry of many potentially therapeuticpeptide drugs to the brain. Glycosylation has shown potential as a methodology for improving delivery to the CNS. Previous studies have shown improved bioavailability and improved centrally mediated analgesia of glycosylatedopioids. In this study we investigate the effect of glycosylation on the cyclic opioid peptide [D-Cys(2.5),Ser(6),Gly(7)] enkephalin. The peptide wasglycosylated on the Ser(6) via an O-linkage with various sugar moieties and alignments. The peptides were then investigated for receptor binding, physiochemical attributes, in situ brain uptake in female Sprague-Dawley rats and antinociception in male ICR mice. Glycosylation resulted in a slight decrease in affinity to the delta -opioid receptor, and mixed effect on binding to the mu -opioid receptor. There was a significant decrease in lipophilicity resulting from glycosylation and a slight reduction in binding to bovine serum albumin. In situ perfusion showed that brain uptake was improved by up to 98% for several of the glycosylated peptides, and the nociceptive profiles of the peptides, in general, followed the rank order of peptide entry to the brain with up to a 39-fold increase in A.U.C. (C) 2000 Elsevier Science B.V. All rights reserved.

ASDD Area Sistemi Dipartimentali e Documentali, Università di Bologna, Catalogo delle riviste ed altri periodici
Documento generato il 02/04/20 alle ore 02:51:58