Sequence-directed

SCHEME 9.21 Sequence directed alkylation by a quinone methide conjugate. 

The discovery of the base-paired, double-helical structure of deoxyribonucleic acid (DNA) provides the theoretic framework for determining how the information coded into DNA sequences is replicated and how these sequences direct the synthesis of ribonucleic acid (RNA) and proteins. Already clinical medicine has taken advantage of many of these discoveries, and the future promises much more. For example, the biochemistry of the nucleic acids is central to an understanding of virus-induced diseases, the immune re-sponse, the mechanism of action of drugs and antibiotics, and the spectrum of inherited diseases. 

The sulfonium ylide derived chemistry of penicillins continues to meet the interest of several research groups. It is well known that intermolecular carbenoid attack at the sulfur atom generates a sulfonium ylide which undergoes spontaneous opening of the thiazolidine ring to furnish a l,2-sm>-penicillin 326). Novel examples of this reaction type were found upon Rb2(0Ac)4-catalyzed decomposition of diazomalonic esters in the presence of various penicillins this transformation constituted the opening step of a synthetic sequence directed towards 2-alkoxycarbonyl-cephems 345 a) or modified penicillins 345 b). Similar to its reaction with 4-thio-2-azetidinone... 

It is clear that pulse sequences may not only be designed by analytical means, they may also be designed numerically (see, e.g., reviews on numerical aspects of solid-state NMR in [54, 65, 66]) using standard nonlinear optimization to well-defined analytical expressions [67, 68], by optimizing pulse sequences directly on the spectrometer [69], or by optimal control procedures [70-72] to name but a few of the possibilities. We will in this review restrict ourselves to optimal control design procedures that recently in analytical and numerical form have formed a new basis for efficient NMR experiment design. 

Plants have the ability to assemble immunoglobulin heavy chains and light chains to form full-length antibodies very efficiently [24]. In mammalian plasma cells, the assembly mechanism is only partially understood. The immunoglobulin light and heavy chains are synthesized as precursor proteins, and signal sequences direct... 

McDonnell, A. V., Menke, M., Palmer, N., King, J., Cowen, L., and Berger, B. (2006). Fold recognition and accurate sequence-structure alignment of sequences directing beta-sheet proteins. Proteins 63, 976-985. 

Roth AF, Sullivan DM, Davis NG (1998) A large PEST-like sequence directs the ubiquitination, endocytosis and vacuolar degradation of the yeast a-factor receptor.) Cell Biol 142 946-961... 

Photophysical Probes of DNA Sequence-Directed Structure and Dynamics... 

Prokaryotic genes encode protein sequences directly with no intervening noncoding DNA, so that mRNA transcripts serve as direct templates for protein synthesis. 

Harrington, R.E. and Winicov, I. New concepts in protein-DNA recognition sequence directed DNA bending and flexibility (1994) Progr. Nucl. Add Res. Mol. Biol. 47,195-270... 

The most important element in many of these targeting pathways is a short sequence of amino acids called a signal sequence, whose function was first postulated by Gunter Blobel and colleagues in 1970. The signal sequence directs a protein to its appropriate location in the cell and, for many proteins, is removed (luring transport or after the protein has reached its final destination. In proteins slated for transport into mitochondria, chloroplasts, or the ER, the signal sequence... 

Other examples of the uses of enolate derivatives of thioesters for highly diastereoselecave aldol reactions were reported by Gennari [373] and Hanaoka et al. [374. 375]. The latter reported the reaction between a chromium-complexed benzaldehyde (1) and the titanium enolate of a thioester (2) as the first step of sequences directed towards the synthesis of (+)-goniofufurone [374] and the taxol C13 side-chain [375]. They also used cobalt-complexed acetylenic aldehydes for the selective formation of syn-aldols [376]. 

Fig. 1. Structure of the expression cassette of a typical bacterial expression plasmid designed to produce an antibody Fab linked to a foreign gene (FG), pelB leader sequences direct penplasmic secretion of the nascent chains. The remainder of the plasmid contains the ampiciilin resistance gene and a plasmid origin of replication.

By using various nucleic acid-sequence-directed EDTA Fe(II) chelates it will become possible to advance genetic manipulation technology and possibly develop novel chemotherapeutic agents. 

Leonhardt H, Page AW, Weier HU, Bestor TH. A targeting sequence directs DNA methyltransferase to sites of DNA replication in mammalian nuclei. Cell... 

Alternatively, promoters could be identified by mapping mRNA sequences directly against the genome. If the mRNA transcript sequence... 

In many process simulations, the user is responsible for structuring all computations and the computational sequence directly. In ASPEN the system is capable of complete automatic determination of the computational sequence. Alternatively, the user can select certain tear streams and can, in fact, easily specify the entire sequence. 

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