Linked Life Data

12797773

Source:http://linkedlifedata.com/resource/pubmed/id/12797773

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
24
pubmed:dateCreated
2003-6-11
pubmed:abstractText
Hybrid peptide-polyketides are a class of medically and biologically important natural products characterized by stereochemical and functional diversity. In their biosynthesis, hybrids are often macrocyclized to achieve rigid structures that populate bioactive conformations. We herein present a chemoenzymatic strategy to access the stereochemical and functional diversity found in macrocyclic hybrid natural products in a manner amenable to efficient library synthesis. Our method makes use of small building blocks in the form of Fmoc-protected epsilon-amino acids containing embedded polyketide functionality. The building block approach allows for combinatorial synthesis of linear molecules that can be activated as soluble thioesters or tethered to a solid-phase resin. We demonstrate that these linear molecules are substrates for macrocyclization by a tolerant catalyst, TycC TE, derived from a nonribosomal peptide synthetase. The method should allow for access to diverse structures with hybrid peptide-polyketide character that can be screened for improved or novel activities.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Jun
pubmed:issn
0002-7863
pubmed:author
pubmed:issnType
Print
pubmed:day
18
pubmed:volume
125
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
7160-1
pubmed:dateRevised
2008-1-17
pubmed:meshHeading
pubmed:year
2003
pubmed:articleTitle
Chemoenzymatic route to macrocyclic hybrid peptide/polyketide-like molecules.
pubmed:affiliation
Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, P.H.S., Research Support, Non-U.S. Gov't