Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UNIPROT:P20366 (substance P)
 21,176 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A lysosomal pepstatin-insensitive proteinase (CLN2p) deficiency is the underlying defect in the classical late-infantile neuronal ceroid lipofuscinosis (LINCL, CLN2). The natural substrates for CLN2p and the causative factors for the neurodegeneration in this disorder are still not understood. We have now purified the CLN2p from bovine brain to apparent homogeneity. The proteinase has a molecular mass of 46 kDa and an aminoterminal sequence, L-H-L-G-V-T-P-S-V-I-R-K, that is identical to the human enzyme. Peptide: N-glycosidase F and endoglycosidase H treatment of the CLN2p reduced its molecular mass to 39.5 and 40.5 kDa, respectively, suggesting the presence of as many as five N-glycosylated residues. The CLN2p activity was not affected by common protease inhibitors, and thiol reagents, metal chelators, and divalent metal ions had no significant effect on the proteolytic activity of the CLN2p. Among the naturally occurring neuropeptides, angiotensin II, substance P, and beta-amyloid were substrates for the CLN2p, whereas angiotensin I, Leu-enkephalin, and gamma-endorphin were not. Peptide cleavage sites indicated that the CLN2p is a tripeptidyl peptidase that cleaves peptides having free amino-termini. Synthetic amino- and carboxyl-terminal peptides from the subunit c sequence, which is the major storage material in LINCL, are hydrolyzed by the CLN2p, suggesting that the subunit c may be one of the natural substrates for this proteinase and its accumulation in LINCL is the direct result of the proteinase deficiency.
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PMID:Purification and characterization of bovine brain lysosomal pepstatin-insensitive proteinase, the gene product deficient in the human late-infantile neuronal ceroid lipofuscinosis. 1061 31

A bioactive peptide containing a glutamine-linked oligosaccharide was chemo-enzymatically synthesized by use of the solid-phase method of peptide synthesis and the transglycosylation activity of endo-beta-N-acetylglucosaminidase. Substance P, a neuropeptide, is an undecapeptide containing two L-glutamine residues. A substance P derivative with an N-acetyl-D-glucosamine residue attached to the fifth or sixth L-glutamine residue from the N-terminal region was chemically synthesized. A sialo complex-type oligosaccharide derived from a glycopeptide of hen egg yolk was added to the N-acetyl-D-glucosamine moiety of the substance P derivative using the transglycosylation activity of endo-beta-N-acetylglucosaminidase from Mucor hiemalis, and a substance P derivative with a sialo complex-type oligosaccharide attached to the L-glutamine residue was synthesized. This glycosylated substance P was biologically active, although the activity was rather low, and stable against peptidase digestion. The oligosaccharide moiety attached to the L-glutamine residue of the peptide was not liberated by peptide-N(4)-(N-acetyl-beta-D-glucosaminyl) asparagine amidase F.
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PMID:Chemo-enzymatic synthesis of a bioactive peptide containing a glutamine-linked oligosaccharide and its characterization. 1141 Mar 33

The chemo-enzymatic synthesis of a glycopeptide, which involves the chemical synthesis of N-acetylglucosaminyl peptide and the enzymatic transfer of oligosaccharide, is described. The first step of the chemo-enzymatic method is the chemical synthesis of N-acetylglucosaminyl peptide with an N-acetylglucosamine moiety bound to the asparaginyl residue of the peptide by a solid-phase method. The second step is transglycosylation of a complex-type oligosaccharide derived from a glycopeptide to an N-acetylglucosaminyl peptide by endo-beta-N-acetylglucosaminidase of Mucor hiemalis (Endo-M). Peptide T can block HIV infection of human T cells. We added the sialo-complex-type oligosaccharide to chemically synthesized N-acetylglucosaminyl Peptide T using the transglycosylation activity of Endo-M. The glycosylated Peptide T thus produced showed a higher degree of resistance to protease digestion than Peptide T. We also prepared calcitonin glycopeptide. Calcitonin is a calcium-regulating hormone that is widely used in therapy for hypercalcemia, and is glycosylated by the chemo-enzymatic method described above. This glycopeptide demonstrated sufficient physiological activity. Comparison of NMR data between native calcitonin and calcitonin glycopetide revealed that the glycosylation does not affect the binding topology of the peptide. N-Acetylglucosaminyl glutamine was also a good glycoside acceptor of Endo-M. We were able to add the sialo-complex-type oligosaccharide to the glutamine residue of the Substance P neuropeptide using the transglycosylation activity of Endo-M. The glycosylated Substance P was biologically active, although its activity was rather low, and stable against peptidase digestion. The oligosaccharide moiety attached to the l-glutamine residue of the peptide was not liberated by PNGase that liberated asparagine-linked oligosaccharide from glycopeptides.
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PMID:Chemo-enzymatic synthesis of bioactive glycopeptide using microbial endoglycosidase. 1623 37