The Role of the 11-cis-retinal Ring Methyl Substituents in Visual Pigment Formation.
From: Departamento de Química Orgánica, Facultade de Química, Universidade de Vigo, 36310 Vigo, Spain.
Chembiochem : a European journal of chemical biology
- Publish Date: Nov 2006
- ISSN: 1439-4227
- Volume: 7
- Issue: 11
- Pages: 1815-25
- Medium: Print
- Language: English
- Citation (JAMA): Domínguez Marta, Alvarez Rosana, Pérez Martín, et al. The Role of the 11-cis-retinal Ring Methyl Substituents in Visual Pigment Formation.. Chembiochem Nov 2006;7:1815-25
Abstract
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.
Mesh Headings (Keywords): Binding Sites, Methylation, Models, Molecular, Protein Structure, Tertiary, Retinal Pigments, Retinaldehyde, Spectrum Analysis
Check for Full Text / PubMed Unique Identifier (PMID): 16941510
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