Macromolecular sites

The drug receptors are macromolecular sites which are situated on the surface or inside the effector cells with which specific agonist combines to produce its response. Antago-... 

Components of a soluble macromolecular site-specific delivery system... 

Macromolecular Sites of Activity for the Trichothecenes. All the trichothecenes tested act, in eukaryotic systems, at the site of the 60s ribosome subunit and specifically inhibit peptidyl transferase. However, the trichothecenes are divided into two specific classes relative to this activity and are either initation inhibitors or elongation and/or termination inhibitors. The initiation inhibitors ares 15-acetoxyscirpen-diol 4-acetylnivalenol diacetoxyscirpenol HT-2 toxin nivalenol T-2 toxin scirpentriol verrucarin A (4-0, 11b). 

A novel method has been proposed [203-205] for obtaining polymeric sorbents with prearranged macromolecular sites for complexing with transition metal ions. Cobalt complexes with the prearranged sorbent were tested as catalysts by the liquid-phase oxidation of styrene and ethylbenzene. These catalysts could be used repeatedly without a decrease in activity. The catalytic activity of polyacrylonitrile and polypropargyl methacrylate complexes with Co was studied during ethylbenzene oxidation reactions [206, 207]. 

It is possible to justify Eq. (4) as follows The maximum number of contacts between a macromolecule and solvent molecules is given by the first portion of the far side of Eq. (4) [(z - 2)x/i2]- The coordination about a single unit of the macromolecule is given by z, and the -2 accounts for the two directions along which the macromolecule continues. This total number of macromolecular sites is to be multiplied by the site fraction on the macromolecules which is actually occupied by the smaller molecules. The site fraction is approximated by the volume fraction of small molecules v. The total number of contacts between macromolecules and small molecules must still be multiplied by some interaction parameter, Ah>i2- Equation (4), indicates that some simplifications are possible. The first one is that the product xn 2y can be replaced by the simpler product iV2. This can easily be seen from the definitions of the volume fractions. Next, the two constants, the coordination number (z - 2) and the interaction parameter (Am/j 2) be combined and expressed in units of RT. This new interaction parameter is commonly denoted by the letter %. It represents the total interaction energy per macromolecular volume element in units of RT. Making these substitutions leads to Eqs. (5) and (6). Note that AG has a quadratic... 

Ca ions exchanging with two macromolecular sites with a binding constant > 10 M . ... 

R and M M Hann 2000. The In Silico World of Virtual Libraries. Drug Discovery Today 5 326-336. R and I D Kuntz 1990. Conformational Analysis of Flexible Ligands in Macromolecular eptor Sites. Journal of Computational Chemistry 13 730-748. 

The spatial and steric requirements for high affinity binding to protein kinase C (PKC), a macromolecule that has not yet been crystallized, were determined. Protein kinase C plays a critical role in cellular signal transduction and is in part responsible for cell differentiation. PKC was identified as the macromolecular target for the potent tumor-promoting phorbol esters (25). The natural agonists for PKC are diacylglycerols (DAG) (26). The arrows denote possible sites of interaction. 

One important class of integral equation theories is based on the reference interaction site model (RISM) proposed by Chandler [77]. These RISM theories have been used to smdy the confonnation of small peptides in liquid water [78-80]. However, the approach is not appropriate for large molecular solutes such as proteins and nucleic acids. Because RISM is based on a reduction to site-site, solute-solvent radially symmetrical distribution functions, there is a loss of infonnation about the tliree-dimensional spatial organization of the solvent density around a macromolecular solute of irregular shape. To circumvent this limitation, extensions of RISM-like theories for tliree-dimensional space (3d-RISM) have been proposed [81,82],... 

From the various autocorrelation times which characterized macromolecular fluctuations, those associated with the fluctuation of the electrostatic field from the protein on its reacting fragments are probably the most important (see Ref. 8). These autocorrelation times define the dielectric relaxation times for different protein sites and can be used to estimate dynamical effects on biological reactions (see Chapter 9 for more details). 

It is now a common feeling that our world cannot survive as it is without plastics [1]. Starting from 1930, when the macromolecular concept started to gain acceptance in the scientific community [2], the advances in polymer science have been so striking that plastics have invaded almost every aspect of modern human life, both as daily materials and as sophisticated substrates able to cover high-tech applications [3]. A very easy and simple way to check this assertion is to visit the The Macrogalleria web site (1st floor) [4] where an extensive exemplification of the most common and important plastic applications in different fields is provided in a really immediate and impressive way. 

FIG. 6 Successive coupling of two different biotinylated compounds with the DNA-STV conjugates 2 [33]. In a first step, a macromolecular functional component (FC, represented by the shaded ellipse), such as a biotinylated enzyme or oligonucleotide, is coupled. In a second step, a biotinylated low-molecular-weight modulator M, represented by the shaded sphere) is coupled to the remaining free biotin-binding sites. The modulator is used to modify the conjugate s hybridization properties or to supplement its functionality. 

DREAM++ A set of programs (ORIENT++, REACT++ and SEARCH++) for docking computationally generated ligands into macromolecular binding sites University of California [31]... 

Another very important site for drug delivery is the central nervous system (CNS). The blood-brain barrier presents a formidable barrier to the effective delivery of most agents to the brain. Interesting work is now advancing in such areas as direct convective delivery of macromolecules (and presumably in the future macromolecular drug carriers) to the spinal cord [238] and even to peripheral nerves [239]. For the interested reader, the delivery of therapeutic molecules into the CNS has also been recently comprehensively reviewed... 

Table 6 Considerations in the Pharmaceutical Development and Clinical Use of Both Soluble Macromolecular and Particulate Biotechnical and Site-Specific Drug-Delivery... 

Quantum mechanics is essential for studying enzymatic processes [1-3]. Depending on the specific problem of interest, there are different requirements on the level of theory used and the scale of treatment involved. This ranges from the simplest cluster representation of the active site, modeled by the most accurate quantum chemical methods, to a hybrid description of the biomacromolecular catalyst by quantum mechanics and molecular mechanics (QM/MM) [1], to the full treatment of the entire enzyme-solvent system by a fully quantum-mechanical force field [4-8], In addition, the time-evolution of the macromolecular system can be modeled purely by classical mechanics in molecular dynamicssimulations, whereas the explicit incorporation... 

Recently, highly branched macromolecular polyamidoamine dendrimers have been prepared with Co11 bound where the metal ions have additional exchangeable coordination sites.450 These macromolecules show a capacity for catalyzing the hydrolysis of phosphate esters, presumably via intermediate bound phosphoester species. 

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