Design rational

Even when an enzyme is studied exhaustively, identifying the amino acid residues that control the catalytic activity is a difficult task In fact, site-specific single mutations rarely do their job, since single mutations far from the active site can change the protein s properties. 

Silaffins-Derived Biomimetic Sequences Based on Poiyamines 

1 Long-Chain Polyamines Silica Formation and Morphogenesis Control 

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Flow chart showing the design of novel orally active HIV-1 protease inhibitor. (Figure adapted from Lam P K ]adhav, C E Eyermann, C N Hodge, Y Ru, L T Bacheler, ] L Meek, M ] Otto, M M Rayner, Y N V /ong, ang, P C Weber, D A Jackson, T R Sharpe and S Erickson-Viitanen 1994. Rational Design of Potent, able. Nonpeptide Cyclic Ureas as HIV Protease Inhibitors. Science 263 380-384.)... 

Rating programs Rational design Rational drug discovery Rauwolfia serpentina Rauwolscine [131-03-3]... 

Penam Sulfone B-Lactamase Inhibitors. Natural product discoveries stimulated the rational design of p-lactamase inhibitors based on the readily accessible penicillin nucleus. An early success was penicillanic acid sulfone, (2(5)-cis)-3,3-dimethyl-7-oxo-4,4-dioxide-4-thia-l-a2abicyclo [3.2.0]heptane-2-carboxylic acid [68373-14-8] (sulbactam) (25, R = = H, R" = R" = CH ), CgH NO S. The synthesis (118), microbiology (119—121),... 

Plate-Column Capacity The maximum allowable capacity of a plate for handling gas and liquid flow is of primaiy importance because it fixes the minimum possible diameter of the column. For a constant hquid rate, increasing the gas rate results eventually in excessive entrainment and flooding. At the flood point it is difficult to obtain net downward flow of hquid, and any liquid fed to the column is carried out with the overheaa gas. Furthermore, the column inven-toiy of hquid increases, pressure drop across the column becomes quite large, and control becomes difficult. Rational design caUs for operation at a safe margin below this maximum aUowable condition. 

Chemoinformatics (or cheminformatics) deals with the storage, retrieval, and analysis of chemical and biological data. Specifically, it involves the development and application of software systems for the management of combinatorial chemical projects, rational design of chemical libraries, and analysis of the obtained chemical and biological data. The major research topics of chemoinformatics involve QSAR and diversity analysis. The researchers should address several important issues. First, chemical structures should be characterized by calculable molecular descriptors that provide quantitative representation of chemical structures. Second, special measures should be developed on the basis of these descriptors in order to quantify structural similarities between pairs of molecules. Finally, adequate computational methods should be established for the efficient sampling of the huge combinatorial structural space of chemical libraries. 

SI Cho, W Zheng, A Tropsha. Rational combinatorial library design 2. Rational design of targeted combinatorial peptide libraries using chemical similarity probe and the inverse QSAR approaches. J Chem Inf Comput Sci 38 259-268, 1998. 

McKinlay, M.A., Rossmann, M.G. Rational design of antiviral agents. Annu. Rev. Pharmacol. Toxicol. 29 111-122, 1989. 

The voluminous experimental information about the linkage between structural variables and properties of polymers is assembled in books, notably that by van Krevelen (1990). In effect, such books encapsulate much empirical knowledge on how to formulate polymers for specific applications (Uhlherr and Theodorou 1998). What polymer modellers and simulators strive to achieve is to establish more rigorous links between structural variables and properties, to foster more rational design of polymers in future. 

The key to a rational design process is establishing a set of mechanistic relationships that relate the configuration to its performance. Use of those mechanistic relationships is what distinguishes the structural designer from a dress designer. 

As a summary of nonlinear behavior, it appears possible to eliminate the nonlinear behavior, and at the same time, you typically do not want to operate in that nonlinear behavior regime anyway, so you are both able to, and want to, design out nonlinear behavior. That observation is true generally in aircraft structures, but there are other structures, which are subjected to higher temperatures, for which you simply cannot avoid some of the nonlinear behavior aspects, so you must take them into account in any rational design analysis. 

Rational design must include the arrangement of processing areas, storage areas, and handling areas with regard to such factors as... 

Coordination as the motif in the rational design of supramolecular metallacyclic polygons and polyhedra 97ACR502. 

The brush-type (Pirkle-type) CSPs have been used predominantly under normal phase conditions in LC. The chiral selector typically incorporates tt-acidic and/or n-basic functionality, and the chiral interactions between the analyte and the CSP include dipole-dipole interactions, n-n interactions, hydrogen bonding, and steric hindrance. The concept of reciprocity has been used to facilitate the rational design of chiral selectors having the desired selectivity [45]. 

Rational design, 148-149, 152 Real-time assays, 83, 88 Receptor(s). See also Drug receptors affinity for, 6, 63 allosteric model of, 143 Clark s work, 3 classical model of, 44-45 concept of, 2-4 conformations, 13-14, 13 Of conservation equation for, 76 constitutive activity of, 49-51 coupling of, 27 definition of, 2 desensitization of, 34 efficacy for, 6... 

So far there is no cover-all recipe for remedying these undesirable phenomena yet recommendations have been made for some special cases which included proper choice of process conditions and methods, rational design of molds and articles allowing one to minimize the negative effect of filler and matrix orientation in the manufacturing process [370],... 

A number of rationally designed MMP inhibitors have shown some promise in the treatment of pathologies, which MMPs are suspected to be involved in. However, most of these, such as Marimastat (BB-2516), a broad spectrum MMP inhibitor, or trocade (Ro 32-3555), an MMP-1 selective inhibitor, have performed poorly in clinical trials. The failure of Marimastat was partially responsible for the folding of British Biotech, which developed it. The failure of... 

Nelfinavir is a nonpeptidic, rationally designed HIV protease inhibitor. Nelfinavir has demonstrated efficacy in both monotherapy and in combination with the reverse transcriptase inhibitors stavudine (d4T) or zivudine + 3TC. The major side effect is mild to moderate diarrhea. 

Modem methods for the manuf and storage of expl materials, which include many exotic chemicals, fuels, and propints, allow less space for a given quantity of expl material than previously permitted. Such concns of expls increase the possibility of the propagation of accidental explosions (one accidental explosion causing the detonation of other expl materials). It was evident that a requirement for more accurate design techniques had become essential. Ref 3 describes a rational design method to provide the required structural protection. It presents methods of design for protective construction... 

There are various ways in which CMEs can benefit analytical applications. These include acceleration of electron-transfer reactions, preferential accumulation, or selective membrane permeation. Such steps can impart higher selectivity, sensitivity, or stability to electrochemical devices. These analytical applications and improvements have been extensively reviewed (35-37). Many other important applications, including electrochromic display devices, controlled release of drugs, electrosynthesis, and corrosion protection, should also benefit from the rational design of electrode surfaces. 

Because of the unambiguous reactive sites of monomers and the high chemo-and stereoselectivity of transition-metal-catalyzed coupling reactions, polymers prepared by transition metal coupling have predictable chemical structures. Functional groups can be easily and selectively introduced at the desired position within die polymer chains. Therefore, polymers widi specific properties can be rationally designed and synthesized. 

The predictable stereochemistry of the ring closure of substituted 5-hexenyllithiums, coupled with the ease with which the product organolithium may be functionalized, permits rational design of synthetic routes to polycyclic systems by sequential anionic cyclizations of polyolefinic alkyllithiums.12 The preparation of stereoisomerically pure e do-2-substituted bicyclo[2.2.1]heptanes is illustrative of this approach to polycyclic systems.12... 

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