Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: EC:3.2.1.17 (lysozyme)
 21,489 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The crystal structures of HCO-Met-Leu-Phe-OC(CH3)3, (CH25H39N3O5S), fMLP-OtBu, and HCO-Met psi [CSNH]-Leu-Phe-OCH3, (C22H33N3O4S2), fMS LP-OMe, have been determined by single crystal X-ray diffraction, and their conformational properties investigated by molecular mechanics energy calculations. Crystals of fMLP-OtBu are monoclinic, space group P2(1), a = 12.027(4), b = 9.492(3), c = 12.660(4) A, beta = 101.99(3) degrees, Z = 2; those of fMS LP-OMe are orthorhombic, space group P2(1)2(1)2(1), a = 7.130(1), b = 12.097(2), c = 31.060(5) A, Z = 4. The first compounds fMLP-OtBu is the t-butyl ester of the tripeptide fMLP that represents one of the most potent compounds in inducing the lysozyme release from human neutrophils that reflects the chemotactic activity. From the crystal structure, it is shown that the orientation of the phenylalanine side chain is largely affected by the presence of the bulky group. fMSLP-OMe was shown to be inactive after thionation of the methionine residue in the original tripeptide. Nevertheless, the crystal structure does not reveal any influence of the presence of the thionated peptidic bond on the backbone conformation. The X-ray results have been used to generate parameters for empirical energy calculations. Subsequently, a strategy based on random generation of conformations followed by energy-minimization was applied to investigate the conformational space of thiopeptides, in comparison with normal peptides. From molecular free energy calculations, it is shown that the main influence of the introduction of a thioamide bond on the molecular structure is to prevent the existence of C7(eq) conformations involving the thiomethionine residue. Consequently, a larger number of conformers are found to form intramolecular hydrogen bonds involving the formyl group, reducing its availability to interact with the receptor. For the first time, the theoretical prediction of the existence of C7eq conformations for fMLP is made. The resulting conformers are compared to previously active structures of these chemotactic agents.
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PMID:Crystal and molecular structure of two geometrically restricted chemotactic tripeptides, analogues of formyl-methionine-leucine-phenylalanine. 209 Jun 40

The effect of modification of maleimide derivatives on superoxide production by guinea-pig neutrophils induced by a variety of different soluble stimuli was studied. Pretreatment of neutrophils by showdomycin, a very slowly penetrating-SH reagent, did not affect superoxide production by all of the stimuli used, suggesting no exposure of sulfhydryl groups involved in superoxide-generating system on the cell surface. Pretreatment with N-ethylmaleimide (MalNEt), a considerably penetrating-SH reagent, markedly inhibited superoxide production stimulated by formyl-methionyl-leucyl-phenylalanine (HCO-Met-Leu-Phe), cytochalasin E or digitonin, but not superoxide production stimulated by the ionophore A23187 or sodium fluoride. The oxygen consumption stimulated by HCO-Met-Leu-Phe or cytochalasin E was inhibited by MalNEt pretreatment, whereas the oxygen consumption stimulated by A23187 was not inhibited by MalNEt. The inhibition by MalNEt of superoxide production did not appear to be due to the interference with binding of the affected stimuli, since MalNEt pretreatment did not inhibit the release of lysozyme, granule enzyme, induced by HCO-Met-Leu-Phe, cytochalasin E or digitonin. Particulate fractions from MalNEt-pretreated neutrophils before exposure to the stimulus exhibited the inhibition of the enhancement of NADPH-dependent superoxide production induced by HCO-Met-Leu-Phe, cytochalasin E or digitonin, but not A23187, whereas treatment of neutrophils with MalNEt after activation by these stimuli had no effect on the NADPH oxidase activity in particulate fractions. Direct exposure of particulate fractions from A23187-stimulated neutrophils to MalNEt showed no actual susceptibility of NADPH oxidase to MalNEt inhibition. These findings suggest that the inhibitory effect of MalNEt is caused by the modification of the process of the activation by the affected stimuli of the superoxide system, probably NADPH oxidase and that at least two mechanisms exist for activation of superoxide-generating system in guinea-pig neutrophils on the basis of the susceptibility to MalNEt inhibition.
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PMID:Effect of maleimide derivatives on superoxide-generating system of guinea-pig neutrophils stimulated by different soluble stimuli. 609 85

Veillonella alcalescens subsp. dispar was grown in a synthetic medium containing either radiolabeled thymidine or uridine to monitor cell lysis by assay of the release of deoxyribonucleic acid or ribonucleic acid (RNA), respectively. Biochemical analyses demonstrated that, although human or hen egg white lysozymes alone did not release deoxyribonucleic acid or RNA, the nucleic acids were liberated in equal amounts from lysozyme-treated cells by the addition of low concentrations of the sodium salts of HCO-3, SCN-, Cl-, and F-, RNA release was dependent on enzyme and anion concentration. Human lysozyme was more potent than hen egg white lysozyme, and bicarbonate was the most effective anion in promoting bacteriolysis. Surprisingly, ultrastructural analyses differed from biochemical results. Lysozyme alone caused lysis in approximately 40% of the cell population. Detailed ultrastructural examination revealed aggregated cytoplasmic components which appeared as small clumps, explaining why nucleic acids were not measurable in the biochemical assays. In reaction mixtures containing lysozyme plus inorganic salts, electron microscopy results were compatible with biochemical data. Ultrastructural studies demonstrated that the addition of inorganic salts to lysozyme-treated cells resulted in the solubilization of the protoplasmic aggregates of lysed cells, presumably freeing the complexed RNA, and in the rapid lysis of the remaining cells (approximately 60%). These data suggest that electron microscopy must be used in conjunction with biochemical assays to assess lytic damage of bacterial cells.
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PMID:Bacteriolysis of Veillonella alcalescens by lysozyme and inorganic anions present in saliva. 616 67

Streptococcus mutans GS5 was grown in synthetic medium containing radioactive thymidine to monitor deoxyribonucleic acid release. At neutral pH, cell lysis of hen egg-white lysozyme- or lysozyme-protease-treated cells was dependent upon the nature and concentration of the additive inorganic anions, HCO-3, SCN-, Cl- or F-. At acidic pH, NaHCO3, but not NaSCN, NaCl or NaF, was effective in promoting cell lysis which was due not only to the change in pH but also to the new HCO-3 anion concentration at the new pH. In both pH 4 and 5.2 reaction mixtures, the lysozyme and trypsin acted synergistically with NaHCO3 and the amount of lysis produced was markedly greater than in reaction mixtures containing lysozyme and bicarbonate but no protease. At apparent sub-lytic concentrations of NaHCO3, lysis was achieved by adding an appropriate concentration of one of NaSCN, NaCl or NaF to the lysozyme-protease-damaged cells. Thiocyanate proved to be most effective among the anions requiring lower concentrations to elicit lysis compared to chloride or fluoride for a fixed sub-lytic concentration of bicarbonate. As the NaHCO3 concentration increased, the lysis in the presence of these other anions increased until maximum levels of released deoxyribonucleic acid (DNA) were attained. In addition, the higher the NaHCO3 concentration, the more marked was the change in the degree of cell lysis. At a selected concentration at which NaHCO3 was not effective with any one salt, lysis could be achieved by combining all four inorganic anions at this concentration. The results suggest that the various anions present in oral fluids may together be sufficient to trigger lysis of oral microorganisms.
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PMID:Synergism of lysozyme, proteases and inorganic monovalent anions in the bacteriolysis of oral Streptococcus mutans GS5. 631 51

The new fMLP analog HCO-Hmb-Leu-Phe-OMe (1), containing (S)-2-hydroxy-4-(methylthio)butyric acid (Hmb) in place of L-methionine at the N-terminal position, has been synthesized and fully characterized. The peptide 1 has been designed in order to improve the understanding of the role exerted by the formamido group in the binding interaction with the formylpeptide chemotactic receptors. Chemotaxis, superoxide anion production, and lysozyme release have been measured for both 1 and its deformylated analog Hmb-Leu-Phe-OMe 2. Results indicate that a strong hydrogen bond of the OH....O = C type may complement a weak H-bonding interaction involving the formylic proton as H-bond donor.
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PMID:Synthesis and chemotactic activity of the fMLP analog HCO-Hmb-Leu-Phe-OMe. 821 43

The new C alpha-tetrasubstituted alpha-amino acid residue 2-[2'-(methylthio)ethyl]methionine (Dmt) has been introduced into the reference chemotactic tripeptide HCO-Met-Leu-Phe-OMe (fMLP-OMe) in place of the leucine or methionine, respectively. The biological activity of the new analogues [Dmt2]fMLP-OMe (2) and [Dmt1]fMLP-OMe (3) has been determined; whereas 2 is active toward human neutrophils, stimulating directed migration, superoxide anion generation, and lysozyme release, 3 results practically inactive in all tested assays. A conformational analysis on 2 and 3 has been performed in solution by using ir absorption and 1H-nmr. The conformation of 2 was also examined in the crystal by x-ray diffraction methods. Both 2 and 3 adopt fully extended conformation in correspondence with the Dmt residue. Biological and conformational results are discussed and compared with related previously studied models.
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PMID:Synthesis, conformation, and biological activity of two fMLP-OMe analogues containing the new 2-[2'-(methylthio)ethyl]methionine residue. 928 91

In order to obtain chemotactic peptides with selective bioactivity, a new type of structural modification was introduced at the N-terminal position of HCO-Nle-Leu-Phe-OMe. Two groups of analogs have been synthesized both containing a N-terminal residue of the X=C(R)-CO-type replacing the native HCO-NH-CH(R)-CO-. In particular, the A group of pseudopeptides (2a-d) possesses a N-terminal oximic fragment (X=HO-N) and the B group (3a-d) a formylhydrazone fragment (X=HCO-NH-N). These new ligands have been examined for their capacity to induce chemotaxis and other cellular responses such as superoxide anion production and lysozyme release; although significantly active as chemoattractants they have been found to be practically devoid of secretagog activity, thus exhibiting selective behavior. The adopted chemical modification seems extensible in designing a new class of pseudopeptides (hydrazonopeptides) structurally related to both hydrazinopeptides and peptides containing alpha,beta-unsaturated residues.
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PMID:Bioactive fMLF-OMe analogs containing a N-terminal oximic or formylhydrazonic moiety. 1078 26

We report here the synthesis and activity of new analogs of the N-formyl and N-tert-butyloxycarbonyl (Boc) derivatives of the tripeptide Met-Leu-Phe-OMe containing an achiral omega-amino acid residue replacing the hydrophobic central leucine. The tripeptides HCO-Met-NH-(CH2)n-CO-Phe-OMe and Boc-Met-NH-(CH2)n-CO-Phe-OMe (n = 3-5) containing the central homomorphic residue of 5-aminopentanoic acid (delta-aminovaleric acid; delta-Ava; n = 4) and the two non-homomorphic residues of 4-aminobutanoic acid (gamma-aminobutyric acid; gamma-Abu; n = 3) and 6-aminohexanoic acid (epsilon-aminocaproic acid; epsilon-Aca; n = 5) have been examined. The activity as agonists and antagonists in chemotaxis, lysozyme release, and superoxide anion production of the new analogs has been determined. The N-Boc derivatives 2a and 2b, incorporating the gamma-Abu and the delta-Ava residues, show good and selective antagonist activity on superoxide anion production.
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PMID:Synthesis and activity on human neutrophil functions of fMLF-OMe analogs containing alkyl spacers at the central position. 1176 37

In order to explore the properties of chemotactic N-formylpeptides containing isopeptide bonds within their backbones, a group of lysine-containing analogs of the prototypical chemotactic tripeptide N-formylmethionyl-leucyl-phenylalanine (fMLF) was synthesized. The new analogs were designed by adding to the HCO-Met or Boc-Met residue a dipeptide fragment made up of Lys and Phe residues joined through Lys N alpha or N epsilon bonds, in all possible combinations. Thus, the following six pairs of tripeptides were synthesized and examined for their bioactivity: RCO-Met-Lys(Z)-Phe-OMe (2a, b), RCO-Met-Lys(Z-Phe)-OMe (3a, b), Z-Lys(RCO-Met)-Phe-OMe (4a, b), Z-Phe-Lys(RCO-Met)-OMe (5a, b), RCO-Met-Phe-Lys(Z)-OMe (6a, b) and Z-Lys(RCO-Met-Phe)-OMe (7a, b), with R=OC(CH3)(3 )and R=H for compounds a and b, respectively. All the new models were characterized fully and their activity (chemotaxis, superoxide anion production and lysozyme release) on human neutrophils determined as agonists (compounds b) and antagonists (compounds a). All N-formyl derivatives 2b-7b are less potent than fMLF-OMe as chemoattractants, but compound 7b exhibits selective activity as superoxide anion producer. Derivatives 2a-7a do not show antagonistic activity towards fMLF induced chemotaxis and O(2)(-) production, however, all these compounds except 4a antagonize lysozyme release by 60%.
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PMID:Isopeptide bonds in chemotactic tripeptides. Synthesis and activity of lysine-containing fMLF analogs. 1201 May 19

New synthetic analogues of the chemotactic N-formyltripeptide HCO-Met-Leu-Phe-OMe have been synthesized. The reported new models, namely Boc-Met-beta-Ala-Phe-OMe (1), HCO-Met-beta-Ala-Phe-OMe (2), Boc-Met-Tau-Phe-OMe (3), HCO-Met-Tau-Phe-OMe (4) and HCl.Met-Tau-Phe-OMe (5), are characterized by the presence at the central position of a residue of beta-alanine or 2-aminoethanesulfonic acid (taurine) replacing the native L-leucine. Whereas tripeptides 1 and 2 have been found quite inactive as chemoattractants, all the three models containing the Tau residue exhibit a remarkable activity. Superoxide anion production and lysozyme release have been also evaluated and the biological results are discussed together with the conformational preferences of the examined models.
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PMID:Synthesis and activity of HCO-Met-Leu-Phe-OMe analogues containing beta-alanine or taurine at the central position. 1457 63


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