Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.11 (CD10)
 9,792 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Anion exchange chromatography resolves two charge variants of rat kidney endopeptidase-24.11 (designated NEP 1 and NEP 2); each was purified to homogeneity using immunoaffinity chromatography. In addition to charge differences the subunit molecular weights of NEP 1 and NEP 2 differ and are 89 and 96 kDa, respectively. Isoelectric focusing resolved 8-10 pl species in the pH range of 5.95-6.20 for NEP 1 and 5.46-6.06 for NEP 2. Removal of sialic acid residues converted the multiple pl species to one form with a pl of 6.32 for NEP 2, and two forms with pls of 6.27 and 6.32 for NEP 1. Endoglycosidase H or F, capable of removing high-mannose and biantennary branched N-linked oligosaccharides, produced a 2-3 kDa decrease in the molecular weight of both NEP 1 and NEP 2. Peptide-N-glycosidase F, capable of removing all classes of N-linked oligosaccharides, produced 8 and 11 kDa decreases in NEP 1 and NEP 2, respectively. Removal of all N-linked and O-linked oligosaccharides with trifluoromethanesulfonic acid resulted in 10 and 15 kDa decreases in NEP 1 and NEP 2, respectively. Tryptic epitope maps demonstrated that NEP 2 was cleaved at a slower rate than NEP 1. These analyses demonstrate that rat kidney NEP exhibits sialic acid microheterogeneity resulting in two distinct change variants. The data also indicate that NEP 2 contains more N- and O-linked carbohydrate mass than NEP 1 and may contain a larger polypeptide backbone giving rise to molecular weight differences between these enzyme forms.
 ...
PMID:Glycosylation variants of endopeptidase-24.11 ('enkephalinase'). 151 62

Since there is no consensus sequence directing the initial GalNAc incorporation into mucin peptides, O-glycosylation sites are not reliably predictable. We have developed a mass spectrometric sequencing strategy that allows the identification of in vivo O-glycosylation sites on mucin-derived glycopeptides. Lactation-associated MUC1 was isolated from human milk and partially deglycosylated by trifluoromethanesulfonic acid to the level of core GalNAc residues. The product was fragmented by the Arg-C-specific endopeptidase clostripain to yield tandem repeat icosapeptides starting with the PAP motif. PAP20 glycopeptides were subjected to sequencing by post-source decay matrix-assisted laser desorption ionization mass spectrometry or by solid phase Edman degradation to localize the glycosylation sites. The masses of C- or N-terminal fragments registered for the mono- to pentasubstituted PAP20 indicated that GalNAc was linked to the peptide at Ser5,Thr6 (GSTA) and Thr14 (VTSA) but contrary to previous in vitro glycosylation studies also at Thr19 and Ser15 located within the PDTR or VTSA motifs, respectively. Quantitative data from solid phase Edman sequencing revealed no preferential glycosylation of the threonines. These discrepancies between in vivo and in vitro glycosylation patterns may be explained by assuming that O-glycosylation of adjacent peptide positions is a dynamically regulated process that depends on changes of the substrate qualities induced by glycosylation at vicinal sites.
 ...
PMID:Localization of O-glycosylation sites on glycopeptide fragments from lactation-associated MUC1. All putative sites within the tandem repeat are glycosylation targets in vivo. 931 74

Synthetic routes to highly functionalized 1,4-thiazepinones 2 and 3 have been developed. S-Ac-N-Boc-L-Cys-D(L)-ThrOMe 7a,b have been prepared and, after transformation into the corresponding mesylates, used as the cyclization substrates. Treatment of these compounds with LiAlH(OMe)(3) in THF results in mesylate elimination and thiolacetate reduction, giving rise to both a Michael acceptor (alpha,beta-unsaturated ester) and Michael donor (thiol anion), which undergo in situ intramolecular conjugate addition leading to the stereoselective formation of only two of the four possible stereoisomers of 2. On the other hand, PCC/CaCO(3) oxidation of 7a gave in 80% yield the corresponding ketone 11, which was in turn transformed into the enol triflate 15. Cleavage of the thiolacetate moiety, simultaneous elimination of trifluoromethanesulfonic acid to generate an allene system, and addition of the thiol group to the central carbon of the allene to provide the enantiomerically pure cyclic compound 3 in 85% yield was effected via a one-pot reaction by means of MeONa/MeOH. Thiazepinone 3 is an interesting intermediate for the preparation of conformationally restricted dipeptide mimetics, and its elaboration into the dual ACE/NEP inhibitor 4 is reported.
 ...
PMID:Cyclic Dipeptides. 3.(1) Synthesis of Methyl (R)-6-[(tert-Butoxycarbonyl)amino]-4,5,6,7- tetrahydro-2-methyl-5-oxo-1,4-thiazepine-3-carboxylate and Its Hexahydro Analogues: Elaboration of a Novel Dual ACE/NEP Inhibitor. 1167 97