Linked Life Data

12372830

Source:http://linkedlifedata.com/resource/pubmed/id/12372830

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:dateCreated
2002-11-28
pubmed:abstractText
Cyclic and linear peptides containing the Asn-Gly-Arg (NGR) motif have proven useful for delivering various anti-tumor compounds and viral particles to tumor vessels. We have investigated the role of cyclic constraints on the structure and tumor-homing properties of NGR peptides using tumor necrosis factor-alpha (TNF) derivatives containing disulfide-bridged (CNGRC-TNF) and linear (GNGRG-TNF) NGR domains. Experiments carried out in animal models showed that both GNGRG and CNGRC can target TNF to tumors. However, the anti-tumor activity of CNGRC-TNF was >10-fold higher than that of GNGRG-TNF. Molecular dynamic simulation of cyclic CNGRC showed the presence of a bend geometry involving residues Gly(3)-Arg(4). Molecular dynamic simulation of the same peptide without disulfide constraints showed that the most populated and thermodynamically favored configuration is characterized by the presence of a beta-turn involving residues Gly(3)-Arg(4) and hydrogen bonding interactions between the backbone atoms of Asn(2) and Cys(5). These results suggest that the NGR motif has a strong propensity to form beta-turn in linear peptides and may explain the finding that GNGRG peptide can target TNF to tumors, albeit to a lower extent than CNGRC. The disulfide bridge constraint is critical for stabilizing the bent conformation and for increasing the tumor targeting efficiency.
pubmed:language
eng
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:author
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
47891-7
pubmed:dateRevised
2006-11-15
pubmed:articleTitle
Structure-activity relationships of linear and cyclic peptides containing the NGR tumor-homing motif.
pubmed:affiliation
Consiglio Nazionale delle Ricerche, Istituto di Chimica del Riconoscimento Molecolare (CNR)-ICRM, 20131 Milan, Italy.