Conformational specificity

Although the directives allow flexibility in the methods and solutions that a manufacturer may employ to fulfil the essential requirements, they promote the use of standards as the preferred method to establish conformity. Specifically, the directives stipulate that Member States shall presume compliance with the essential requirements in respect of devices that are in conformity with relevant harmonised standards. 

Brandsch, M., et al. Evidence for the absolute conformational specificity of the intestinal H+/peptide symporter, PEPT1. /. Biol. Chem. 1998, 273, 3861-3864. 

MO s and the butadienic pi MO s is not in the same direction. Consequently, the MO overlap integrals will play the key role in determining the relative stabilization of the two conformers. Specifically, the ns( s) MO is lower in energy than the ng (tarns)... 

Analogues in which one or more of the naturally occurring peptide bonds in a substrate, effector, or ligand has been replaced by some other chemical structure. Such compounds are useful in characterizing binding specificity (particularly conformational specificity), and... 

Conformation-specific gel electrophoresis is a variant of CDGE that uses mildly denaturing solvents in an appropriate buffer to accentuate conformational changes produced by single-base mismatches in heteroduplexed DNA. This increases the differences in electrophoretic mobility between heteroduplex and homoduplex. 

Ginsberg, M. H., Frelinger, A. L., Lam, S. C. T., Forsyth, J., McMillan, R., Plow, E. F., and Shattil, S. J., Analysis of platelet aggregation disorders based on flow cytometric analysis of membrane glycoprotein llb-llla with conformation specific monoclonal antibodies. Blood 76, 2017—2023... 

Thiyagarajan M, Samuelson LA, Kumar J, ChoUi AL (2003) Helical conformational specificity of enzymatically synthesized water-soluble conducting polyanUine nanocomposites. J Am Chem Soc 125(38) 11502-11503... 

The two transitions for tryptophan exhibit distinct features, which lead to quite different CD bands. The La transition is broad, relatively featureless, and intense (Fig. B3.5.2). The Lb transition is weaker but exhibits fine structure (Fig. B3.5.2) similar to that of tyrosine. It can be masked by or superimposed on the La transition. Interactions similar to those listed for tyrosine strongly affect the peak wavelengths and intensities. The presence of bands above 285 nm is diagnostic for tryptophan in a specific environment interactions that cause the Lb transition to be shifted to the red (or high-wavelength) end of the spectrum result in bands as high as 310 nm which are highly conformation-specific. The two transitions may be affected quite independently by interactions, and their combination can thereby result in four distinct types of spectrum (Strickland, 1974). 

Wakabayashi, K., Sakata, Y., and Aoki, N. 1986. Conformation-specific monoclonal antibodies to the calcium-induced structure of protein C. J. Biol. Chem. 267 11097-11105. 

Jiang S, Lin K, Lu M (1998) A conformation-specific monoclonal antibody reacting with fusion-active gp41 from the HIV-1 envelope glycoprotein. J Virol 72 10213-10217... 

The essential realization in this spontaneous ordering process is the importance of noncovalent bonding interaction between molecules, that is, supramolecular chemistry. These conformation-specific interactions are governed by weak forces including hydrogen bonding, metal coordination, van der Waals forces, pi-pi interactions, and electrostatic Coulombic effects. The cooperative action of multiple noncovalent interaction forces is precisely the path nature takes to produce shape and form. 

These footprinting analyses, based on enzymic and chemical digestion, are now widely used to define DNA (and RNA) and their complexes with various ligands. Recently active radical probes have been used as footprinting agents in protection assays in a variety of systems (e.g., Tullius and Dombroski, 1986 Chalepakis and Beato, 1989 Hayes and Tullius, 1989 Schickor et al., 1990). Such probes rely on active radical intermediates, most likely hydroxyl radicals, released by Fe(II) in the presence of an electron donor, probably via a Fenton reaction. In addition, hydroxyl radicals also appear to react with DNA in a conformation-specific manner which may allow some prediction of DNA secondary structure (see Burkhoft and Tullius, 1987 Zorbas et al., 1989 Lu et al., 1990). 

Although assembled antigenic sites are more numerous, both sites are topographic in that they are composed of structures on the protein surface. However, an antibody exerts high-affinity binding to segmental sites only when those sites are in a preferred conformation. Therefore, all determinants must be conformation specific. 

The search for an enzymatic activity that would catalyze prolyl peptide bond isomerization began soon after the proposal of the proline hypothesis. The success came in 1984, when Fischer and co-workers discovered a peptidylprolyl m—tram-isomerase activity in porcine kidney and other tissues by an assay that is based on the conformational specificity of chymotrypsin. This protease cleaves the 4-nitroanilide moiety from the peptide glutaryl-Ala-Ala-Pro-Phe-4-nitroanilide only when the Ala-Pro peptide bond is in the trans conformation. In aqueous solution 90% of the molecules are trans in the assay peptide and only 10% are cis. Therefore, in the presence of a high concentration of chymotrypsin, 90% of the hydrolysis reaction occurs within the dead time of manual mixing. Hydrolysis of the remaining 10% is slow, limited in rate by the cis — ... 

The pyrolysis of A -oxides of 3a- and 3/S-dimethylamino-5ct-cholestane (e.g. 17) confirms the accepted ws-character of the elimination reaction, which leads to olefins [42]. The two A/ -oxides afforded similar yields of olefins [32], in contrast to the conformationally specific reactions of the corresponding quaternary salts. 

Burgess MR, Skaggs BJ, Shah NP, Lee FY, Sawyers CL. Comparative analysis of two clinically active BCR-ABL kinase inhibitors reveals the role of conformation-specific binding in resistance. Proc Natl Acad Sci USA 2005 102 3395-400. 

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