Conformation defined

Consider a diffusion process in which a molecule is initially in a conformation defined by the coordinates rj,. A transition probability can be constructed using a product of joint probabilities /5(r(,+i rj,) for moving between intermediate positions rj, and rj,+ i integrated over all intennediate states,... 

Thermodynamically it would be expected that a ligand may not have identical affinity for both receptor conformations. This was an assumption in early formulations of conformational selection. For example, differential affinity for protein conformations was proposed for oxygen binding to hemoglobin [17] and for choline derivatives and nicotinic receptors [18]. Furthermore, assume that these conformations exist in an equilibrium defined by an allosteric constant L (defined as [Ra]/[R-i]) and that a ligand [A] has affinity for both conformations defined by equilibrium association constants Ka and aKa, respectively, for the inactive and active states ... 

That the sweet and bitter responses are intimately associated is clear from the results of gustatory studies of all of the conformationally defined sugars and of other organic compounds. If a carbohydrate has any taste at all, this is invariably sweet, bitter-sweet, or bitter. Chemical modification may alter the taste of a sweet compound so that the product is bitter-sweet or bitter, and it is now generally agreed that the two basic tastes may each be a feature of a single compound. It appears, therefore, that the interactions of these polyfunctional stimulants involve two different sets of receptor sites, representing sweet and bitter modalities. ... 

PPII helix-forming propensities have been measured by Kelly et al. (2001) and A. L. Rucker, M. N. Campbell, and T. P. Creamer (unpublished results). In the simulations the peptide backbone was constrained to be in the PPII conformation, defined as (0,VO = ( — 75 25°, +145 25°), using constraint potentials described previously (Yun and Hermans, 1991 Creamer and Rose, 1994). The AMBER/ OPLS potential (Jorgensen and Tirado-Rives, 1988 Jorgensen and Severance, 1990) was employed at a temperature of 298° K, with solvent treated as a dielectric continuum of s = 78. After an initial equilibration period of 1 x 104 cycles, simulations were run for 2 x 106 cycles. Each cycle consisted of a number of attempted rotations about dihedrals equal to the total number of rotatable bonds in the peptide. Conformations were saved for analysis every 100 cycles. Solvent-accessible surface areas were calculated using the method of Richmond (1984) and a probe of 1.40 A radius. 

The preceding prediction rules are largely restricted to acyclic compounds. But there is also a considerable need for parameter sets enabling the spectroscopist to calculate I3C chemical shifts of conformationally defined cyclic molecules, especially of the cyclohexane type. Methyl-group effects in methylcyclohexanes (100,101) that are to be added to the basic value for cyclohexane itself (8 = 27.3) are listed in Table 29. Analogous methyl-group parameters in tetralins and tetra-hydroanthracenes have been reported (403). 

Pleiss, M.A. and Grunewald, G.L. An extension of the f-fragment method for the calculation of hydrophobic constants (Log F) of conformationally defined systems, / Merf Chem., 26(12) 1760-1764,1983. 

In proteins, specific combinations of the dihedral angles c ) and / (see p. 66) are much more common than others. When several successive residues adopt one of these conformations, defined secondary structures arise, which are stabilized by hydrogen bonds either within the peptide chain or between neighboring chains. When a large part of a protein takes on a defined secondary structure, the protein often forms mechanically stable filaments or fibers. Structural proteins of this type (see p. 70) usually have characteristic amino acid compositions. 

Other things being equal, it appears that the stability of the complexes are higher the better the ligand can envelop the cation and replace its coordination shell. The results show that an optimal ligand should be fairly rigid and held in a conformation defining a spherical cavity. 

Kedarcidin is a chromoprotein anti-tumor antibiotic, produced by an actinomycete strain. It is an acidic complex with an apparent molecular weight of 12,400 Da, and it consists of an apoprotein and a cytotoxic highly unstable nonprotein chromophore 12 that possesses a conformationally defined ansamacrocyclic bridge. Retrosynthetically,... 

Toward a screening program for RhuA stereoselectivity, structurally more simplified dioxane derivatives 25-27 comprising enantiomeric and diastereomeric 3-hydroxyaldehyde geometries in a conformationally defined environment could be prepared easily from carbohydrate precursors (Scheme 2.2.5.10). First results from product analysis provide further evidence for occasionally biased fixation of... 

Scheme 1 Conformations Defined by Hydrogen-Bonding Patterns and a 3-Turn Conformation...

The syntheses of heterostranded coiled coils are presented (Section 13.2.2.4), as are templates and conformationally defined peptide libraries (Sections 13.2.4 and 13.2.4.1). Finally, Section 13.1 concludes with a presentation of the methods for characterization of the coiled coils including circular dichroism, microcalorimetry, size-exclusion chromatography, and analytical ultracentrifugation (Section 13.2.5). 

Using the Coiled-Coil Template for Conformationally Defined and Constrained Combinatorial Peptide Libraries... 

Peptide libraries made up of millions of randomized peptide sequences have proven useful for the identification of novel ligands that may be of interest for the development of medicinally active compounds.[123,124] However, due to the short length of the individual peptides in linear peptide libraries, they possess considerable conformational flexibility and can populate multiple random-like conformations. This flexibility does not allow one to determine the precise three-dimensional orientation of the side chains, which greatly impedes structure-based design. These facts have greatly accelerated studies into conformationally restricted libraries, where constraints have been introduced to decrease peptide flexibility. However, what is really required is the design of conformationally defined and constrained templates for library display. These templates present the side chains of selected residues in a defined three-dimensional space. Thus, as an alternative to linear peptide libraries, the well-char-... 

The main purpose of this section has been to highlight the rapid progress over recent years in studies of ligand-receptor interactions at a molecular level, and the new opportunities that arise for peptide mimetic design. This also emphasizes the need for new approaches and molecular tools in the design of conformationally defined, small molecule peptide and protein mimetics, which is the main topic of the remaining sections in this article. 

The conformation of C-lactose (25a, R = H) bound to peanut lectin agglutinin has been studied through X-ray analysis.11 The bound conformation, defined by o —63, I c 120°, is practically identical to that of the parent O-lactose (25b, R = H) bound to the same protein. ( o —69, I c 118°). The authors were tempted to conclude from this particular observation that the conformational similarity in protein-bound states is a general phenomenon. Nevertheless, it is clear that the architecture of the binding site should also be analyzed (see later). In contrast, Espinosa et al.12 and Asensio et al.90 demonstrated that the three staggered conformations of C-lactose (syn-exo-<(>, syn- it syn-exo-d>, anti- H and anti-exo-, syn-ty) are recognized by three different proteins, and in some cases their behavior differs from that with natural lactose. 

For polysaccharide, choose connectivity (01-C[l-6]), anomer (alpha or beta), isomer (l or d), and conformation (define phi and psi angle with omega = 180). Add sugars (alsohexoses or aldopentoses) to build polysaccharide chain. 

As we have seen earlier, [tj] may be calculated directly from the (absolute) MAES measurements of M and using Eq. (5). For linear polymers spanning a relatively broad molecular range (an order of magnitude or more), the measurement of M and permits the determination of the molecular conformation defined by... 

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