Active covalent

Romiplostim (AMG 531) is a member of new class of therapeutics called "peptibodies," which are peptides with key biologic activities covalently linked to antibody fragments that serve to extend the peptide s half-life. Romiplostim contains two disulfide-bonded human Fc fragments, each covalently attached through a polyglycine sequence to a peptide... 

Addition of Prosthetic Groups Many prokaryotic and eukaryotic proteins require for their activity covalently bound prosthetic groups. Two examples are the biotin... 

In allosteric enzymes, the activity of the enzyme is modulated by a non-covalently bound metabolite at a site on a protein other than the catalytic site. Normally, this results in a conformational change, which makes the catalytic site inactive or less active. Covalent modulated enzymes are interconverted between active and inactive forms by the action of other enzymes, some of which are modulated by allosteric-type control. Both of these control mechanisms are responsive to changes in cell conditions and typically the response time in allosteric control is a matter of seconds as compared with minutes in covalent modulation. A third type of control, the control of enzyme synthesis at the transcription stage of protein synthesis (see Appendix 5.6), can take several hours to take effect. 

Theoretically, inverse agonists may be useful agents for the treatment of disease symptoms caused by constitutive receptor activity. Covalent modifications of the receptor protein, pathological increase in receptor or G protein densities, or inherited or somatic point mutations may lead to increased constitutive receptor activity. For example, certain inherited point mutations in rhodopsin have been shown to cause retinitis pigmentosa. The involvement of inherited, constitutively activating receptor point mutations has also been demonstrated in certain forms of hyperthyroidism, in male precocious puberty, and in Jansen-type metaphyseal chondrodysplasia [8]. Constitutive G protein activity may also be an important factor in autoimmune diseases [9]. 

Lunn, C. A., Davies, L., Dalgarno, D., Narula, S. K., Zavodny, P. J., and Lundell, D. (1992a). An active covalently linked dimer of human interferon-gamma. Subunit orientation in the native protein. J. Biol. Chem. 267, 17920-17924. 

Under hypoxic conditions, 1,1-dichloroethane gives rise to free radicals. However, its ability to develop free radicals is much less when compared to other chlorinated hydrocarbons like trichloroethane and carbon tetrachloride. It has been suggested that these free radicals possess the potential to induce toxic and carcinogenic effects. There is no correlation between the ease of free radical activation, covalent binding formation, or carcinogenic potency (Tomasi et al. 1984)... 

However, most often, aggregation is not desired. The presence of a nonnative aggregate is a cause of concern to biopharmaceutical scientists because this aggregate may have altered activity, clearance, and toxicity compared with the native protein. Aggregates of ribonuclease A were found to be less active. " Covalent aggregates of insulin resulted in the appearance of antibodies to the protein in the blood of insulin-using diabetic patients. ... 

See also Covalent Modifications to Regulate Enzyme Activity, Covalent Modification of Proteins... 

Keywords Metabolic activation Covalent binding Drug discovery... 

For a molecule to absorb infrared radiation, the bond rmdergoing vibration must be polar, and its vibration must cause a periodic change in the bond dipole the greater the polarity of the bond, the more intense is the absorption. Any vibration that meets this criterion is said to be infrared active. Covalent bonds in homonuclear diatomic molecules, such as Hg and Br2, and some carbon-carbon double bonds in symmetrical alkenes and alkynes do not absorb infrared radiation because they are not polar bonds. The multiple bonds in the following two molecules, for example, do not have a dipole moment and, therefore, are not infrared active ... 

Prior to our work, Hawkins and Meyer had performed the kinetic optical resolution of the inherently chiral fiillerene D2-C76 by employing the asymmetric Sharpless osmylation reaction [17]. A comparison of the circular dichroism (CD) spectra reported by I wkins and Meyer for the C76 enantiomers that they obtained [17] to those of a variety of optically active, covalent derivatives of C76, prepared by us [18] revealed a large, unexpected difference in the magnitude of the Cotton effects. Whereas our covalent C76 derivatives displayed bands reaching Ae values up to 250 M cm , the enantiomers of the pure hillerenes reported by Hawkins and Meyer displayed bands widi Ae values up to only 32 M cm [17, 19]. In order to reinvestigate the chiroptical... 

Multifunctional monomers forming three or more active covalent bonds make three-dimensional networks (Figure A.ld) and are termed network polymers. Actually, a polymer that is highly crosslinked may also be classified as a network polymer. These materials have distinctive mechanical and thermal properties the epoxies, polyurethanes, and phenol-formaldehyde belong to this group. 

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