Linked Life Data

16941510

Source:http://linkedlifedata.com/resource/pubmed/id/16941510

Statements in which the resource exists as a subject.
PredicateObject
rdf:type
lifeskim:mentions
pubmed:issue
11
pubmed:dateCreated
2006-10-31
pubmed:abstractText
Artificial visual pigment formation from ring-demethylated retinals was studied in an effort to understand the effect that methyl groups on the chromophore cyclohexenyl ring have on the visual cycle. The stereoselective synthesis of the 11-cis-ring-demethylated analogues involves thallium-accelerated Suzuki cross-coupling reactions and highly stereocontrolled Wittig reactions to form key bonds. Only 11-cis-1,1,5-trisdemethylretinal (2) failed to form an artificial pigment, whilst variable pigment-formation yields were determined for the remaining analogues, increasing with the number (and location) of the chromophore hydrophobic ring methyl groups. Our results with the monodemethylated analogues 11-cis-5-demethylretinal (4) and 11-cis-1-demethylretinal (5) show that the C1-2-CH(3) groups are more important for pigment formation than the C5-CH(3) substituent. This is reflected in the absorption maxima of the artificial pigments, with values closer to that of native rhodopsin for 4. Docking studies based on a rhodopsin crystal structure, however, predict a lower pigment stability for 4 than for 5. Gas-phase DFT (B3LYP/6-31G*) computations of the free-ligand geometries, conformational searches about the C6--C7 bond, and docking studies revealed that, although the conformation of bound 5 is close to that of the native chromophore, the ligand needs to overcome the energy cost of shifting the unbound favored 6-s-trans conformation to the bound 6-s-cis form. In addition, the presence of an extra methyl group at C18 (11-cis-18-methylretinal, 7) is tolerated well and adds further stability to the complex, most probably due to increased hydrophobic interactions.
pubmed:grant
pubmed:language
eng
pubmed:journal
pubmed:citationSubset
IM
pubmed:chemical
pubmed:status
MEDLINE
pubmed:month
Nov
pubmed:issn
1439-4227
pubmed:author
pubmed:issnType
Print
pubmed:volume
7
pubmed:owner
NLM
pubmed:authorsComplete
Y
pubmed:pagination
1815-25
pubmed:dateRevised
2007-12-3
pubmed:meshHeading
pubmed:year
2006
pubmed:articleTitle
The role of the 11-cis-retinal ring methyl substituents in visual pigment formation.
pubmed:affiliation
Departamento de Química Orgánica, Facultade de Química, Universidade de Vigo, 36310 Vigo, Spain.
pubmed:publicationType
Journal Article, Research Support, N.I.H., Extramural