Linked Life Data

19819139

Source:http://linkedlifedata.com/resource/pubmed/id/19819139

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
22
pubmed:dateCreated
2009-10-26
pubmed:abstractText
We report the synthesis and biological activity of a library of aminoalcohol-derived macrocycles from which robotnikinin, a binder to and inhibitor of Sonic Hedgehog, was derived. Using an asymmetric alkylation to set a key stereocenter and an RCM reaction to close the macrocycle, we were able to synthesize compounds for testing. High-throughput screening via small-molecule microarray (SMM) technology led to the discovery of a compound capable of binding ShhN. Follow-up chemistry led to a library of macrocycles with enhanced biological activity relative to the original hit compounds. Differences in ring size and stereochemistry, leading to alterations in the mode of binding, may account for differences in the degree of biological activity. These compounds are the first ones reported that inhibit Shh signaling at the ShhN level.
pubmed:grant
pubmed:commentsCorrections
http://linkedlifedata.com/resource/pubmed/commentcorrection/19819139-10021418, http://linkedlifedata.com/resource/pubmed/commentcorrection/19819139-10984056, http://linkedlifedata.com/resource/pubmed/commentcorrection/19819139-11755396, http://linkedlifedata.com/resource/pubmed/commentcorrection/19819139-11755397, http://linkedlifedata.com/resource/pubmed/commentcorrection/19819139-11890782, http://linkedlifedata.com/resource/pubmed/commentcorrection/19819139-12391318, http://linkedlifedata.com/resource/pubmed/commentcorrection/19819139-12848532, http://linkedlifedata.com/resource/pubmed/commentcorrection/19819139-16408088, http://linkedlifedata.com/resource/pubmed/commentcorrection/19819139-16647304, http://linkedlifedata.com/resource/pubmed/commentcorrection/19819139-16720270, http://linkedlifedata.com/resource/pubmed/commentcorrection/19819139-1693013, http://linkedlifedata.com/resource/pubmed/commentcorrection/19819139-17719493, http://linkedlifedata.com/resource/pubmed/commentcorrection/19819139-18159935, http://linkedlifedata.com/resource/pubmed/commentcorrection/19819139-19151731, http://linkedlifedata.com/resource/pubmed/commentcorrection/19819139-2477715
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1464-3405
pubmed:author
pubmed:issnType
Electronic
pubmed:day
15
pubmed:volume
19
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
6319-25
pubmed:dateRevised
2011-5-25
pubmed:meshHeading
pubmed:year
2009
pubmed:articleTitle
Syntheses of aminoalcohol-derived macrocycles leading to a small-molecule binder to and inhibitor of Sonic Hedgehog.
pubmed:affiliation
GI Unit, Department of Medicine, Massachusetts General Hospital, 55 Fruit Street, Boston, MA 02114, USA. lpeng@partners.org
pubmed:publicationType
Journal Article, Research Support, Non-U.S. Gov't, Research Support, N.I.H., Extramural