Linked Life Data

20827791

Source:http://linkedlifedata.com/resource/pubmed/id/20827791

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
15
pubmed:dateCreated
2010-10-11
pubmed:abstractText
Integrin ?(?)?(3) is overexpressed on endothelial cells of growing vessels as well as on several tumor types, and so integrin-binding radiolabeled cyclic RGD pentapeptides have attracted increasing interest for in vivo imaging of ?(?)?(3) integrin expression by positron emission tomography (PET). Of the cRGD derivatives available for imaging applications, systems comprising multiple cRGD moieties have recently been shown to exhibit highly favorable properties in relation to monomers. To assess the synthetic limits of the cRGD-multimerization approach and thus the maximum multimer size achievable by using different efficient conjugation reactions, we prepared a variety of multimers that were further investigated in vitro with regard to their avidities to integrin ?(?)?(3.) The synthesized peptide multimers containing increasing numbers of cRGD moieties on PAMAM dendrimer scaffolds were prepared by different click chemistry coupling strategies. A cRGD hexadecimer was the largest construct that could be synthesized under optimized reaction conditions, thus identifying the current synthetic limitations for cRGD multimerization. The obtained multimeric systems were conjugated to a new DOTA-based chelator developed for the derivatization of sterically demanding structures and successfully labeled with (68)Ga for a potential in vivo application. The evaluated multimers showed very high avidities-increasing with the number of cRGD moieties-in in vitro studies on immobilized ?(?)?(3) integrin and U87MG cells, of up to 131- and 124-fold, respectively, relative to the underivatized monomer.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Oct
pubmed:issn
1439-7633
pubmed:author
pubmed:issnType
Electronic
pubmed:day
18
pubmed:volume
11
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
2168-81
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Multimerization of cRGD peptides by click chemistry: synthetic strategies, chemical limitations, and influence on biological properties.
pubmed:affiliation
McConnell Brain Imaging Centre, Montreal Neurological Institute, McGill University, Montreal, H3A 2B4 QC, Canada. carmen.waengler@med.uni-muenchen.de
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't