Peptide aldehydes analysis

Several structures of proteasome inhibitor complexes have been determined by X-ray crystal analysis [22, 50, 51]. Calpain inhibitor I (acetyl-L-L-norleudnal) was covalently bound to Thr-1 of the /91, pi and y95 subunits, respectively. This peptide aldehyde inhibitor is attacked by the threonyl Oy to form a hemiacetal. The nor-leucine side chain projects into a pocket with an opening in its side towards a tunnel leading to the particle surface. The leucine side chain at P2 is not in contact with the protein, whilst the leucine side chain at P3 is in contact with the adjacent / -type subunit. 

In contrast to other inactivators of dopamine /3-hydroxylase, p-cresol is unusual in that it does not contain a latent electrophile (Goodhart et al., 1987). Oxidation of the benzylic carbon occurs, as evidenced by production of 4-hydroxybenzyl alcohol as well as the corresponding aldehyde. Inactivation with radiolabeled p-cresol leads to substoichiometric modification of the enzyme, with the majority of the radiolabel distributed between four tryptic peptides (DeWolf et al., 1988). Analysis of two of the peptides indicates that they are of identical sequence, each containing modified tyrosine residues which differ in the structure of the p-cresol-amino acid adduct. A second pathway for inactivation is proposed which requires radical-mediated oxidation of the enzyme without incorporation of the inactivator. 

The prolyl peptides (367) with three different elements of diversity have been designed in a combinatorial way (using Ugi chemistry) as organocatalysts for the Michael addition of aldehydes RCH2CH=0 to -nitrostyrenes in toluene at r.t. over 24 h. The optimized combinations exhibited <98% ee and <97 3 dr. Conformational analysis was used to... 

RP-HPLC is widely apphcable, although pH control must often be applied. Most important application areas include peptide and protein analysis (proteomics), drugs and their metabolites, fatty acids, and also volatile compounds such as aldehydes and ketones, although these require derivatization. 

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