Structural dissection

Alvarez LA, Merola F, Erard M, Rusconi F (2009) Mass spectrometry-based structural dissection of fluorescent proteins. Biochemistry 48 3810-3812... 

Analysis of Privileged Structural Motifs Structure Dissection Rules... 

It is important to note that the applied rules are not the pure retrosynthetic rules. The described structure dissection procedure also takes into account the structures of typical privileged motifs and is directed to the search of structural chemotypes with selective action against particular receptors. 

Tab. 12.3 The number of fragments obtained as a result of structure dissection procedure for the initial 12 540-compound reference database...

Some of the earliest and most complete efforts at structural dissection have been carried through by Cannon and his co-workers at the University of Iowa. These studies were initially directed toward elucidation of the pharmacophoric element within the structure of the emetic agent apomorphine, I. The suggestion by Pinder et al. (2) that the 5,6-dihydroxy-2-aminotetralin fragment was the active moiety was followed in short order by the report of Cannon et al. (3) that the N,N-dimethyl derivative ("M-7") II was a potent emetic in the dog. Additional pharmacology on M-7 provided by Long et al. (4) further illustrated the similarity between I and II. Both... 

Further structural dissection has shown that the essential requirement for an apomorpine-1ike action in the periphery is a relatively rigid fragment where the amino group is tertiary and is held approximately in the plane of the aromatic ring. Within the 2-amino-l,2,3,4-tetrahydronaphthalenes, it is the 5-hydroxy which is essential for emetic and DA2 activity. When the reduced ring is contracted to yield a 2-aminoindan such as 111, substantial activity is still observed (5 ). Thus, the view of... 

Flint J, Taylor E, Yang M, Bolam DN, Tailford LE, Martinez-Fleites C, Dodson EJ, Davis BG, Gilbert HJ, Davies GJ. Structural dissection and high-throughput screening of mannosylglycerate synthase. Nat. Struct. Mol. Biol. 2005 12 608-614. 

Larval Eye Imaginal Discs ), but instead of dissecting the eye-antenna discs and attached structures dissect only the salivary glands (Fig. la, b). 

CONSIDERATION ON THE LOCALITY OF THE DIGITALIS RECOGNITION MATRIX DEDUCED FROM PROTEIN STRUCTURE DISSECTIONS 152... 

The structural dissection of the lavendamycin molecule 40 revealed a quinolinequinone (AB) and p-carboline (CDE) framework. Both these units are historically known and numerous methodologies for them have been formulated. It was therefore, hoped that the synthetic efforts towards 40 would not pose much difficulties. The synthetic tactics towards 40 revolve around the Bischler-Napieralski reaction between p-methyltryptophan and quinaldic acid to construct ring C, and in the process, bridging the two subunits. However, Roger s group preferred to extend the inverse electron demand Diels-Alder reaction, successfully demonstrated for streptonigrin, to the synthesis of lavendamycin. 

In several instances, biogenetic hypotheses that were based on structural dissections have been confirmed by the results of experiments with iso-topically labelled compounds. But little is yet known about the specific biochemical processes which lead to the synthesis of antibiotics, or about the relationship of these processes to the general biochemistry of the microbial cell. The high yields of streptomycin that are obtainable from certain strains of Streptomyces griseus indicate that a significant fraction of the total metabolic activity of a micro-organism may sometimes be channelled into antibiotic productioni2. 

Schuttelkopf, A. W., Andersen, O. A., Rao, F. V. Screening-based discovery and structural dissection of a novel family 18 chitinase inhibitor. J Biol Chem 2006, 281, 27278-27285. 

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