Tyrosine, covalent bond with

In a 1963 Pedler lecture, Sanger reported that H-DFP makes a covalent bond with tyrosine in the sequence Arg-TjrThrLys from human and rabbit albumin (Sanger, 1963). Mass spectrometry of human albumin treated with soman, chlorpyrifos oxon, FP-biotin, diehlorvos, and DFP confirmed OP modification on Tyr 411 in peptide LVRY TKKVPQVSTPTL (Li et al, 2007, 2008a), where the underline shows Sanger s sequence and the indieates the labeled tyrosine. 

Both forms, however, contained intact RNA and the full complement of capsid polypeptides (50) Further evidence that a substantial conformational alteration of entero- and rhinovirus capsids accompanies the D to C antigenicity change has been obtained by examining the accessibilities of individual capsid proteins in intact virions, A-particles and naturally-occurring empty capsids to lacto-peroxidase-catalyzed iodination or alkylation with acetic anhydride (5I> 52). The results of these experiments are summarized in Table lY. Since under the experimental conditions employed the radioactive reagents formed covalent bonds with tyrosine residues... 

The quinoline-based tyrosine kinase inhibitor pelitinib (31-11) incorporates a Michael acceptor function in the side chain that can form a covalent bond with a nucleophile on the target enzyme. Such an interaction would result in the irreversible inhibition of the target kinase. Reaction of aniline (31-1) with DMF acetal leads to the addition of a carbon atom to aniline nitrogen in the form of an amidine (31-2). This intermediate is next reacted with nitric in acetic acid to form the nitrated... 

Similar mass spectrometry experiments with pure human and mouse transferrin (Li et al., 2008c), and with human kinesin showed that the OP label was consistently on tyrosine (Table 56.1). Studies with human plasma identified OP labeling on tyrosine in apolipoprotein and alpha-2-glyco-protein. Aggressive treatment of hiunan albumin with FP-biotin and chlorpyrifos oxon led to identification of seven OP-labeled tyrosines (Ding et al, 2008). Finally, we found that synthetic peptides made a covalent bond with DFP, chlorpyrifos oxon, and dichlorvos (Table 56.1). Mass spectrometry conclusively proved that the OP was attached to tyrosine. 

OPS MAKE A COVALENT BOND WITH SERINE, THREONINE, TYROSINE, LYSINE, AND HISTIDINE ... 

Although some applications for preparative-scale separations have already been reported [132] and the first commercial systems are being developed [137, 138], examples in the field of the resolution of enantiomers are still rare. The first preparative chiral separation published was performed with a CSP derived from (S -N-(3,5-dinitrobenzoyl)tyrosine covalently bonded to y-mercaptopropyl silica gel [21]. A productivity of 510 mg/h with an enantiomeric excess higher than 95% was achieved for 6 (Fig. 1-3). 

I topoisomerase of mammals is a 100 kD monomeric protein whose activity is ATP-independent. This enzyme binds to double-stranded DNA and cleaves one of the DNA strands of the duplex, simultaneously forming an enzyme-DNA covalent bond between a tyrosine residue and the 3 -phosphate of the cleaved DNA. The type II topoisomerases are dimeric enzymes, which are ATP-dependant. Two isoforms of topoisomerase II exist, topoisomerase a and (3, with apparent molecular weights of 170 and 180 kD. Topoisomerase... 

Figure 16.3 Conceptual illustration of two peptides before (left) and after (right) a chemical reaction with formaldehyde. The amino acids are represented as circles. In this particular peptide, a tyrosine (Y) is located within the epitope (shaded circles). An arginine (R) is located elsewhere in the peptide. Formaldehyde results in the formation of a covalent bond between the two residues, due to a Mannich condensation reaction, as shown on the right. The new configuration prevents antibodies from binding to the epitope on the left. 

The effect of electronic configuration of the acceptor is particularly apparent in the contrast of Ser/Thr and Tyr hydroxyl groups the phenolic hydroxyl of tyrosine has a preference for near-plane position for donors and/or acceptors, as its sp hybridization leaves the lone pair electrons in the plane of the ring [15, 16], whereas serine and threonine hydroxyls have sp hybridization with two acceptor and one donor position at 120° spacing (the donating proton is usually trans to the carbon three covalent bonds away). The observed spatial distributions for the principal amino acid donor and acceptor groups are illustrated schematically in Fig. 6.1. 

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