Linked Life Data

17046402

Source:http://linkedlifedata.com/resource/pubmed/id/17046402

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2006-10-18
pubmed:abstractText
This review considers the design, synthesis, and mechanistic assessment of peptide-based fibrillogenesis inhibitors, mainly focusing on beta-amyloid, but generalizable to other aggregating proteins and peptides. In spite of revision of the "amyloid hypothesis," the investigation and development of fibrillogenesis inhibitors remain important scientific and therapeutic goals for at least three reasons. First, it is still premature to dismiss fibrils altogether as sources of cytotoxicity. Second, a "fibrillogenesis inhibitor" is typically identified experimentally as such, but these compounds may also bind to intermediates in the fibrillogenesis pathway and have hard-to-predict consequences, including improved clearance of more cytotoxic soluble oligomers. Third, inhibitors are valuable structural probes, as the entire field of enzymology attests. Screening procedures for selection of random inhibitory sequences are briefly considered, but the bulk of the review concentrates on rationally designed fibrillogenesis inhibitors. Among these are internal segments of fibril-forming peptides, amino acid substitutions and side chain modifications of fibrillogenic domains, insertion of prolines into or adjacent to fibrillogenic domains, modification of peptide termini, modification of peptide backbone atoms (including N-methylation), peptide cyclization, use of D-amino acids in fibrillogenic domains, and nonpeptidic beta-sheet mimics. Finally, we consider methods of assaying fibrillogenesis inhibitors, including pitfalls in these assays. We consider binding of inhibitor peptides to their targets, but because this is a specific application of the more general and much larger problem of assessing protein-protein interactions, this topic is covered only briefly. Finally, we consider potential applications of inhibitor peptides to therapeutic strategies.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:issn
0076-6879
pubmed:author
pubmed:issnType
Print
pubmed:volume
413
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
273-312
pubmed:dateRevised
2010-11-18
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
Peptide-based inhibitors of amyloid assembly.
pubmed:affiliation
The University of Chicago, Department of Pathology, Chicago, IL, USA.
pubmed:publicationType
Journal Article, Review