Linked Life Data

21510668

Source:http://linkedlifedata.com/resource/pubmed/id/21510668

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
21
pubmed:dateCreated
2011-5-24
pubmed:abstractText
This study focuses on the development of DNA catalysts (deoxyribozymes) that modify side chains of peptide substrates, with the long-term goal of achieving DNA-catalyzed covalent protein modification. We recently described several deoxyribozymes that modify tyrosine (Tyr) or serine (Ser) side chains by catalyzing their reaction with 5'-triphosphorylated RNA, forming nucleopeptide linkages. In each previous case, the side chain was presented in a highly preorganized three-dimensional architecture such that the resulting deoxyribozymes inherently cannot function with free peptides or proteins, which do not maintain the preorganization. Here we describe in vitro selection of deoxyribozymes that catalyze Tyr side chain modification of tethered and free peptide substrates, where the approach can potentially be generalized for catalysis involving large proteins. Several new deoxyribozymes for Tyr modification (and several for Ser modification as well) were identified; progressively better catalytic activity was observed as the selection design was strategically changed. The best new deoxyribozyme, 15MZ36, catalyzes covalent Tyr modification of a free tripeptide substrate with a k(obs) of 0.50 h(-1) (t(1/2) of 83 min) and up to 65% yield. These findings represent an important advance by demonstrating, for the first time, DNA catalysis involving free peptide substrates. The new results suggest the feasibility of DNA-catalyzed covalent modification of side chains of large protein substrates and provide key insights into how to achieve this goal.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
May
pubmed:issn
1520-4995
pubmed:author
pubmed:issnType
Electronic
pubmed:day
31
pubmed:volume
50
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4741-9
pubmed:dateRevised
2011-9-26
pubmed:meshHeading
pubmed:year
2011
pubmed:articleTitle
DNA-catalyzed covalent modification of amino acid side chains in tethered and free peptide substrates.
pubmed:affiliation
Department of Chemistry, University of Illinois at Urbana-Champaign, 600 South Mathews Avenue, Urbana, IL 61801, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S., Research Support, N.I.H., Extramural