Search results for "aminopeptidase"
showing 10 items of 56 documents
Antigen processing influences HIV-specific cytotoxic T lymphocyte immunodominance
2016
Udgivelsesdato: 2009-May-03 Although cytotoxic T lymphocytes (CTLs) in people infected with human immunodeficiency virus type 1 can potentially target multiple virus epitopes, the same few are recognized repeatedly. We show here that CTL immunodominance in regions of the human immunodeficiency virus type 1 group-associated antigen proteins p17 and p24 correlated with epitope abundance, which was strongly influenced by proteasomal digestion profiles, affinity for the transporter protein TAP, and trimming mediated by the endoplasmatic reticulum aminopeptidase ERAAP, and was moderately influenced by HLA affinity. Structural and functional analyses demonstrated that proteasomal cleavage 'prefer…
Synthesis and Inhibitory Studies of Phosphonic Acid Analogues of Homophenylalanine and Phenylalanine towards Alanyl Aminopeptidases.
2020
A library of novel phosphonic acid analogues of homophenylalanine and phenylalanine, containing fluorine and bromine atoms in the phenyl ring, have been synthesized. Their inhibitory properties against two important alanine aminopeptidases, of human (hAPN, CD13) and porcine (pAPN) origin, were evaluated. Enzymatic studies and comparison with literature data indicated the higher inhibitory potential of the homophenylalanine over phenylalanine derivatives towards both enzymes. Their inhibition constants were in the submicromolar range for hAPN and the micromolar range for pAPN, with 1-amino-3-(3-fluorophenyl) propylphosphonic acid (compound 15c) being one of the best low-molecular inhibitors …
A synthetic method for diversification of the P1′ substituent in phosphinic dipeptides as a tool for exploration of the specificity of the S1′ bindin…
2007
Abstract A novel, general, and versatile method of diversification of the P1′ position in phosphinic pseudodipeptides, presumable inhibitors of proteolytic enzymes, was elaborated. The procedure was based on parallel derivatization of the amino group in the suitably protected phosphinate building blocks with appropriate alkyl and aryl halides. This synthetic strategy represents an original approach to phosphinic dipeptide chemistry. Its usefulness was confirmed by obtaining a series of P1′ modified phosphinic dipeptides, inhibitors of cytosolic leucine aminopeptidase, through computer-aided design basing on the structure of homophenylalanyl-phenylalanine analogue (hPheP[CH 2 ]Phe) bound in …
Phosphonic Analogues of Phenylglycine as Inhibitors of Aminopeptidases: Comparison of Porcine Aminopeptidase N, Bovine Leucine Aminopeptidase and Ami…
2019
Inhibitory activity of 14 phosphonic analogues of phenylglycine, substituted in aromatic ring by fluorine and chlorine, was determined towards porcine aminopeptidase N. The obtained data served as a basis for studying their interaction with the enzyme as modelled by the use of Schrödinger Release 2018 program. The observed linearity between modelled Gibbs free energy differences and inhibitory constants indicated the usefulness of this program. The obtained binding mode was compared with this modelled for bovine lens leucine aminopeptidase. Although both enzymes differ in the number of zinc ions present in the active site, they are considered to exhibit similar activity towards sub…
�ber das Verhalten der Leucin-Aminopeptidase-Aktivit�t im Blutserum bei Patienten mit malignen Tumoren im Mund- und Halsbereich
1959
Nach kurzen Hinweis auf Histotopographie und Bedeutung von Peptidasen im Carcinomgewebe wurde uber die Leucin-Aminopeptidase-Aktivitat des Blutserums bei 53 Patienten der Hals-Nasen-Ohrenklinik mit vorwiegend malignen epithelialen Tumoren (Carcinomen) im Mund- und Halsbereich berichtet. Von Fall zu Fall konnten grose Schwankungen der Leucin-Aminopeptidase-Aktivitat im Blutserum festgestellt werden. In etwa einem Drittel der Falle fanden sich erhohte, in einem Drittel normale und in einem weiteren Drittel gegenuber der Norm erniedrigte Leucin-Aminopeptidase-Aktivitaten im Blutserum, jeweils ohne das eine ausreichende Begrundung dafur angegeben werden konnte. Ausgedehnte und metastasierende C…
Leucine Aminopeptidase Activity in Mast Cells
1959
DURING investigations of the behaviour of leucine aminopeptidase activity of blood-serum in patients with dermatoses and tumours1–3, in a case of diffuse skin mastocytosis of a new-born, we detected heightened activity of leucine aminopeptidase. After mechanical friction of the affected skin, greater activity of leucine aminopeptidase occurred. From this we supposed a release of leucine aminopeptidase from the mast cell infiltrates of the skin. As is well known, in urticaria pigmentosa mechanical irritation of the skin lesions give rise to a degranulation of mast cells4,5 with liberation of histamine and serotonin. Indeed, there is no doubt that mast cells contain the enzyme leucine aminope…
Late infantile neuronal ceroid lipofuscinosis: Quantitative description of the clinical course in patients withCLN2 mutations
2002
We examined 26 individuals with clinical and electron microscopic signs of late infantile neuronal ceroid lipofuscinosis (LINCL). In 22 cases, we found both pathogenic alleles. Sixteen patients exclusively carried either one or a combination of the two common mutations R208X and IVS5-1G > C. In the remaining cases, four missense mutations could be detected, of which R127Q, N286S, and T353P represent novel, previously not described alleles. A clinical performance score was developed by rating motor, visual, and verbal functions and the incidence of cerebral seizures in 3-month intervals during the course of the disease. A Total Disability Score was derived by summing up the single scores for…
Differentiation of Penicillium griseofulvum Dierckx isolates by enzyme assays and by patulin and griseofulvin analyses
1990
The production of patulin and griseofulvin by 49 different isolates of Penicillium griseofulvum Dierckx was analyzed by high-performance liquid chromatography. Eleven isolates were obtained from pistachio nuts, 37 were obtained from wheat seeds, and 1 was obtained from the American Type Culture Collection. Activities of 19 enzymes were also assayed by the API ZYM system. From these results it may be deduced that there are two different groups among the strains tested which cannot be distinguished by morphological and cultural characteristics. One group of isolates did not produce detectable amounts of patulin and griseofulvin when grown in sucrose-yeast extract and Wickerham media, while en…
Stereoselective synthesis of 1-aminoalkanephosphonic acids with two chiral centers and their activity towards leucine aminopeptidase
2003
The stereoselective synthesis of 1-amino-2-alkylalkanephosphonic acids, namely, compounds bearing two chiral centers, was achieved by the condensation of hypophosphorous acid salts of (R)(+) or (S)(-)-N-alpha-methylbenzylamine with the appropriate aldehydes in isopropanol. Simultaneous deprotection and oxidation by the action of bromine water provided equimolar mixtures of the RS:RR and SR:SS diastereomers of desired acids. They appeared to act as moderate inhibitors of kidney leucine aminopeptidase with potency dependent on the absolute configuration of both centers of chirality.
A phosphonamidate containing aromatic N-terminal amino group as inhibitor of leucine aminopeptidase-design, synthesis and stability.
2006
Fully deprotected phosphonamidate dipeptides, predicted as effective inhibitors of cytosolic leucine aminopeptidase, showed unexpected instability in water solution at pH below 12. Their hydrolysis rate was strictly correlated with basicity of the N-terminal amino group. To improve this feature a phosphonamidate analogue containing less basic, aromatic 2-aminophenylphosphonate residue in P1 position of the inhibitor was designed. The target compound was synthesised starting from diethyl 2-nitrophosphonate in several step procedure. The decrease in basicity of the terminal amino moiety of the modified analogue in fact resulted in satisfactory improvement of hydrolytic stability of the P–N bo…