Linked Life Data

20210325

Source:http://linkedlifedata.com/resource/pubmed/id/20210325

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
12
pubmed:dateCreated
2010-3-24
pubmed:abstractText
We report the synthesis of two-faced inhibitors 1-5 that contain both enzyme inhibitor and cucurbit[n]uril binding domains. The enzyme binding domains of 1-5 bind to the active sites of bovine carbonic anhydrase (BCA) or acetylcholinesterase (AChE) and inhibit their catalytic activities. Addition of CB[7] to BCA*1 and BCA*2 results in the transient formation of the BCA*1*CB[7] and BCA*2*CB[7] ternary complexes that undergo rapid dissociation to form free catalytically active BCA along with CB[7]*1 and CB[7]*2. The on-off cycle can be performed repetitively by the sequential addition of competitive guest 8 and CB[7]. The detailed origins of this on-off switching of the catalytic activity of BCA is delineated by the combined inference of UV/vis catalytic assays, fluorescence displacement assays, (1)H NMR, along with measurement of the fundamental values of K(a), k(on), and k(off) for the various complexes involved. In contrast, addition of CB[7] to AChE*4(4) and AChE*5(4) results in the formation of thermodynamically stable ternary complexes AChE*4(4)*CB[7](4) and AChE*5(4)*CB[7](4) that are catalytically inactive. We highlight some of the advantages and disadvantages of the strategy, based on the direct competition between two receptors (e.g., enzyme and CB[7]) for a common inhibitor, used in this paper to control enzyme catalytic activity compared to the strategy employed by Nature involving the binding of an allosteric small molecule remote from the enzyme active site.
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Mar
pubmed:issn
1520-5126
pubmed:author
pubmed:issnType
Electronic
pubmed:day
31
pubmed:volume
132
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
4445-54
pubmed:meshHeading
pubmed:year
2010
pubmed:articleTitle
Biological catalysis regulated by cucurbit[7]uril molecular containers.
pubmed:affiliation
Department of Chemistry and Biochemistry, University of Maryland, College Park, Maryland 20742, USA.
pubmed:publicationType
Journal Article, Research Support, U.S. Gov't, Non-P.H.S.