Conformational anchor

Conformational equilibria still fast on the NMR timescale. From reference compounds (diastereomeric analogs, e.g., 4-/err-butyl or 3,5-cis-dimethyl substitution operating as a kind of conformational anchor), the NMR parameters of the purely equatorial and axial conformers (Pcq and Pax, respectively) can be determined. The equilibrium constant K [Eq. (3)] from these parameters and that of the population-weighted observed NMR parameter, P, can be estimated from the fast equilibrium [59CI(L)568] ... 

The simplest case of substrate-controlled diastereoselection is the incorporation of the controlling stereocenter and the prostereogenic center into a cyclohexane or cyclopentane ring. In the classical example of nucleophilic attack on a conformationally anchored cyclohexanone, axial and equatorial attack are possible, leading to diastereomers 1 and 2, respectively. 

The reduction of six-membered ring ketones (conformationally anchored) with sodium borohydride or lithium aluminum hydride to give predominantly the equatorial alcohol with... 

It is, of course, possible that the initial fast phase is reversible. It was concluded that removal of the C-terminal tail allows an active-site conformation to occur during turnover, in which the affinity for FMN is decreased, allowing the cofactor to dissociate from the enzyme. Thus the C-terminal tail is not essential for tetramer formation but appears to act as a conformational anchor, exerting an effect on the structure of the enzyme in regions distant from it, particularly the FMN active site. 

Thirdly, a considerable effort has been directed towards understanding the stcrcodirecting influence of electronegative substituents at C-4 of cyclohexanones89 91. In particular, it has been found that in conformationally anchored systems such substituents can have a very significant influence in promoting axial hydride delivery, provided they are themselves axially directed, e.g., the reduction of the bicyclo[4.4.0]decane systems below89-128. In each case control experiments on comparable equatorially substituted systems revealed effects which were very much smaller. 

An intramolecular cyclization of an ene with a Lewis acid-activated carbonyl also took advantage of low-energy conformers to obtain high selectivity in the reaction. The optically-enriched ketones 75 and 77 underwent Lewis acid promoted cyclization via a chair-chair transition state, which minimized steric interactions and provided quantitative yield of the optically-enriched alcohols 76 and 78, respectively. In this instance, the OTIPS group served as a conformational anchor to result in the stereoselectivity in the cyclization. ... 

Radical bromination of the V-shaped diaryl 52 gave the single exo-bis-bromo derivative 53. The explanation for the high selectivity was attributed to the requirement of the formed radical orbital to be delocalized in the aromatic plane, thereby acting as a radical conformational anchor. ... 

An anchor, as defined above, contains stable molecules, conformers, all pairs of radicals and biradicals formed by a simple bond fission in which no spin re-pairing took place, ionic species, and so on. Figure 1 shows some examples of species belonging to the same anchor. Thus, an anchor is a more general and convenient temi used in the discussion of spin re-pairing. 

There are two main classes of loop modeling methods (1) the database search approaches, where a segment that fits on the anchor core regions is found in a database of all known protein structures [62,94], and (2) the conformational search approaches [95-97]. There are also methods that combine these two approaches [92,98,99]. 

Melikyan GB, Egelhofer M, von Laer D (2006) Membrane-anchored inhibitory peptides capture human immunodeficiency virus type 1 gp41 conformations that engage the target membrane prior to fusion, J Virol 80 3249-3258... 

Yamazaki, S., Sato, K., Suhara, K. et al. (1993) Importance of the proline-rich region following signal-anchor sequence in the formation of correct conformation of microsomal cytochrome P-450s. Journal of Biochemistry, 114 (5), 652-657. 

We wondered why NSCs proliferated exclusively on surfaces with EGF-His ligands anchored by coordination. We focused on two aspects in particular the conformational integrity of coordinated EGF-His and the stability of coordinate bonds at the interface. Conformational information was acquired with multiple internal reflection-infrared absorption spectroscopy (MIR-IRAS) [97]. The stability of coordinate bonds was assessed by culturing NSCs on a surface with a small region of EGF-His ligands anchored by coordination. This spatially restricted EGF-His anchoring enabled an intuitive exploration of EGF-His release under cell culture conditions. 

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