Combinatorial isotope labeling

Fig. 1 Example of a combinatorial isotope labeling scheme that identifies adjacent amino acids in the sequence [106], In this simplified example, backbone structures for the same segment with two differently labeled samples are shown on the left in a and b, with the corresponding 2D...

Today, despite recent developments in combinatorial and other chemosynthetic strategies, flmgi and streptomycetes remain the most prolific sources of new candidate drugs and agrochemicals. Both phyla elaborate bicyclic, tricyclic and tetracyclic fused ring polyketides, however, a preliminary survey of isotopically labelled precursor incorporation studies has revealed a consistent difference in the modes of cyclisation by which their characteristic polybenzenoid metabolites are formed. These and subsequent observations (yide infra) provide the basis for a novel biosynthetic classification of microbial fused ring polyketides. 

Some service firms may restrict themselves to a single business, perhaps temporarily. For examples, the North Carolina firm sarco offers combinatorial chemistry services as do Pharmacopeia in New Jersey and NeoKimia in Quebec. Discovery research services generally include medicinal chemistry by traditional or modem means, custom synthesis, preparation of radiochemicals and stable-isotope-labeled drugs, isolation of drug metabolites, or patent law. 

Fax 410-740-2985 E-mail martek2000 aol.com Internet site www.martekbio.com pharmaceutical products, combinatorial libraries, stable isotope-labeled compounds... 

Amino Acids and Peptides. - Wasserman s method of one-carbon homologation of carboxylic acids to give a-ketocarboxylates involves reaction with cyanomethylenetriphenyl-phosphorane followed by ozone (Scheme 24) and has been used as a key step in a chemo-enzymatic synthesis of isotopically labelled L-valine, L-isoleucine, and o/fo-isoleucine. Alkylation of the carbanion derived from the imino-substituted methylphosphonate diphenyl ester (186) with indol-3-ylmethyl bromide followed by appropriate deprotection has been used to prepare the phosphonate analogue (187) of tryptophan (Scheme 25). The deprotected analogue (188) and derived peptides show activity as inhibitors of chymotrypsin. Two approaches to solid phase Wadsworth-Enunons reactions which have applications in combinatorial chemistry have been reported. In one diethylphosphonoacetamide is bound to PEG-PAL resin via a peptide link, while... 

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