Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: DrugBank:EXPT00572 (Asn)
 11,732 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Determination of the amino acid sequence of the immunogenic polypeptides of hepatitis B surface antigen may not only permit molecular localization of the distinct determinants a, d, and y but may also lead to the synthesis of a hapten useful in prophylactic immunization against hepatitis B virus infection. For this purpose, purified monotypic hepatitis B surface antigen of adw subtype was resolved into equal amounts of two major polypeptides (22,000 and 28,000 daltons) and up to six other minor polypeptides by polyacrylamide gel electrophoresis. With the periodate staining reaction, only the 28,000-dalton polypeptide stained as a glycoprotein. Guinea pigs immunized with the 22,000-dalton polypeptide produced potent antisera against determinants a and d, but the 28,000-dalton glycoprotein did not induce a response. Both polypeptides isolated by preparative polyacrylamide gel electrophoresis showed amino acid composition identical with that of the intact antigen. For both polypeptides, hydrazinolysis gave Ile as the carboxyterminus, and carboxypeptidase A digestion gave the same terminal sequence, Val-Tyr-Ile. Both peptides also yielded an identical sequence of amino acids in nine steps of Edman degradation--Met-Glu-Asn-Ile-Thr-Ser(Cys)-Gly-Phe-Leu. Our data suggest that hepatitis B surface antigen contains a single major immunogenic 22,000-dalton polypeptide component, part of which is modified by the addition of carbohydrate to give rise to the glycopeptide of apparent molecular weight 28,000.
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PMID:Partial amino acid sequence of two major component polypeptides of hepatitis B surface antigen. 26 93

A variant of hepatitis B virus (HBV) having a specific mutation within the S gene has been found to infect vaccinees. To know whether similar variants were involved in Japan, we analyzed two cases of maternal transmission of HBV in infants immunized with hepatitis B immune globulin and hepatitis B vaccine. DNA clones of HBV S genes were propagated from patients and family members and sequenced. In one family, the DNA clones from the baby patient had a Gly-to-Arg mutation at the 145th codon of the S gene, whereas those from her mother had no such mutations. In the other family, all the DNA clones obtained from the two infected children had the 145th codon intact, but they had a missense mutation at the 126th codon of the S gene, causing an amino acid substitution of Asn for Thr or Ile. This same mutation was observed in 12 of 17 clones of DNA obtained from their mother. In comparison with the wild type HBV-derived hepatitis B surface antigen, the two types of S gene mutations, either at the 145th or the 126th codon, were associated with a significant decrease in the antigenicity of some determinants on the hepatitis B surface antigen, measured by MAb. Amino acid substitution at these sites, therefore, would have induced the escape from conventional vaccines that were S gene products of wild type HBV and also from hepatitis B immune globulin, whose main components were probably also antibodies against the S gene products expressed by wild type HBV.
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PMID:Mutations within the S gene of hepatitis B virus transmitted from mothers to babies immunized with hepatitis B immune globulin and vaccine. 138 17

The molecular basis of the biophysical and antigenic differences between the cellular core protein (HBc protein) and the secreted core protein (HBe protein) of human hepatitis B virus was examined. The data show that the properties which distinguish the HBe protein from the HBc protein are due mostly to the 10-amino-acid portion of the HBe leader sequence which remains attached to the HBe protein after cleavage. A cysteine located within this region determines the quaternary structure and the antigenicity of the HBe protein. If this cysteine is lacking, the HBe protein, which is predominantly a monomer with only HBe antigenicity, is expressed as a disulfide-linked homodimer showing both HBe and HBc antigenicity. However, dimerization of the HBe protein was found to be neither sufficient nor required for particle formation. In fact, aggregation of the HBe protein was found to be inhibited by the strongly hydrophobic tripeptide Trp-Leu-Trp, which is also located in the noncleaved portion of the signal sequence. If this tripeptide was converted into either Asp-Asn-Asn or Ala-Asp-Leu, the HBe protein assembled into particles, independent of the presence of the cysteine.
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PMID:A cysteine and a hydrophobic sequence in the noncleaved portion of the pre-C leader peptide determine the biophysical properties of the secretory core protein (HBe protein) of human hepatitis B virus. 150 Dec 77

Epitopes defined by monoclonal antibodies (mAb) specific for the Bordetella pertussis outer membrane protein P.69 (pertactin) were mapped using a series of amino- and carboxy-terminal deletion mutants expressed in Escherichia coli. mAb were found to bind predominantly to a region of pertactin spanning a (Pro-Gln-Pro)5 repeat motif and one mAb was found to bind to another region spanning a (Gly-Gly-Xaa-Xaa-Pro)5 repeat motif. To localize further the mAb-binding sites, a panel of synthetic peptides, a series of 94 overlapping hexameric peptides, and a P.69 30-amino acid fusion to a hepatitis B core protein (HBcAg-69), were synthesized. This combined approach has identified the binding site for the mAb BBO5: Pro-Gly-Pro-Gln-Pro-Pro; mAb BBO7, E4A8 and E4D7: Ala-Pro-Gln-Pro-Pro-Ala-Gly-Arg; and mAb BPE3: Thr-Leu-Trp-Tyr-Ala-Glu-Ser-Asn-Ala-Leu-Ser-Lys-Arg. We have used a non-lethal murine respiratory model of B. pertussis infection to investigate the ability of a peptide containing the epitope of the mAb BBO5 to elicit protective immunity. Immunization of mice with the HBcAg-69 protein prevented growth of B. pertussis in the lungs compared to mice receiving HBcAg alone, and protection correlated with high titers of anti-P.69 antibodies.
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PMID:Identification and characterization of a protective immunodominant B cell epitope of pertactin (P.69) from Bordetella pertussis. 170 65

R16HBsAg is an experimental recombinant malaria vaccine consisting of 16 repeats of a four amino acid sequence (Asn-Ala-Asn-Pro or NANP) of the circumsporozoite (CS) protein of Plasmodium falciparum expressed as a fusion protein with the recombinant hepatitis B virus surface antigen (HBsAg) produced by yeast cells. Twenty male volunteers were experimentally vaccinated with the product, as well as with two doses of the commercial recombinant HBsAg vaccine Engerix B (Smith Kline Beecham Biologicals, Rixensart, Belgium) at intervals during a period of 18 months. No serious side effects were observed. Circulating antibodies to recombinant CS antigen (R32tet32) developed in all volunteers and persisted in most cases over ten months. Anti-HBs antibody production was poor initially, but a single dose of the commercial hepatitis B vaccine was sufficient to elevate these titers to high levels in all but two volunteers.
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PMID:Phase I clinical trial of a recombinant malaria vaccine consisting of the circumsporozoite repeat region of Plasmodium falciparum coupled to hepatitis B surface antigen. 183 11

The effect on hepatitis B surface antigen (HBsAg) of reagents considered specific for each of the amino acid residues, lysine, methionine, cysteine, arginine, tyrosine, tryptophan, and glutamic (aspartic) acid, was studied. Based on the observed alterations of HBsAg antigenicity and the known amino acid sequence of the HBsAg polypeptide, a major antigenic determinant was localized within the sequence: Pro-Ser-Cys-Cys-Cys-Thr-Lys-Pro-Thr(Ser)-Asp-Gly-Asn-Cys-Thr-Cys-Ile-Pro-Ile-Pr o-Ser-Ser, corresponding to residues 135-155. The asparagine-linked saccharide chains are not essential for HBsAg antigenicity.
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PMID:Localization of a hepatitis B surface antigen determinant deduced from results of chemical modifications. 616 48

Recovery from a hepatitis B virus (HBV) infection or vaccination with hepatitis B surface antigen (HBsAg) leads to a physiologic immune response specific for the alpha determinant, common to all subtypes of HBsAg. In contrast, an absence of immune response to the alpha determinant is characteristic of persistent HBV infection as well as of the nonresponders to vaccination. Therefore, our goal is to characterize the alpha determinant for synthesis of a bifunctional vaccine which may be useful for active immunization as well as for the safe termination of immune tolerance to HBsAg in carriers. Because the immunochemical activity of the alpha determinant of HBsAg is dependent upon cysteine and lysine residues that are localized in the hydrophilic stretch between amino acid sequence 121-160, we synthesized the following peptide analogues of HBsAg (HBsPA): 122-137, 128-134, 139-147, 139-158, 140-158, 145-158 and 150-158. Serologic inhibition of human antibodies against the alpha determinant indicated the antigenicity of the HBsPAs containing the Cys-Thr-Lys-Pro-Thr-Asp-Gly-Asn-Cys sequence. After coupling with keyhole limpet hemocyanin (KLH), carrier-peptide conjugates induced in rabbits anti-HBs which was neutralized equally by eight different serotypes of HBsAg. Therefore, HBsPA/139-147 represents an essential part of the alpha determinant. By substituting alpha-aminobutyric acid (Aba) for Cys at residue 147 a homogeneous dimeric form of this nonapeptide was prepared. After coupling with purified tetanus toxoid or KLH as a carrier by means of carbodiimide, the product induced sustained high level anti-HBs/alpha response in carrier-primed rabbits. Experiments in chimpanzees should validate our concept of a bifunctional synthetic vaccine against HBV infection.
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PMID:Appraisal and prospects of a dimeric synthetic peptide coupled with tetanus toxoid for a bifunctional vaccine against hepatitis B virus infection. 619 28

The major polypeptides composing hepatitis B surface antigen (HBsAg) particles are P-I and P-II. P-II shares the same amino acid sequence as P-I and contains an additional carbohydrate moiety of mol. wt approximately 5000. When a purified preparation of P-II was digested with Nagarse and then with Pronase P, it gave rise to a glycopeptide containing 15 amino acid residues and the carbohydrate moiety of P-II. The N-terminal amino acid sequence of the glycopeptide was determined to be Lys-Pro-Thr-Asp-Gly-Asn-. The polysaccharide moiety contained 5 moles of N-acetylglucosamine and was connected with Asn at the sixth position from the N-terminus. When mice were immunized against this HBsAg glycopeptide, they raised humoral antibodies which bound to each of three preparations of P-I derived from HGsAg particles of subtypes adw, adr and ayw, thereby indicating that the sequence of 15 amino acids in the glycopeptide would constitute a common antigenic structure of HBsAg.
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PMID:A glycopeptide containing 15 amino acid residues derived from hepatitis B surface antigen particles: demonstration of immunogenicity to raise anti-HBs in mice. 714 54

Termination mutations in the precore open reading frame of hepatitis B virus (HBV) variants with defective hepatitis B e antigen (HBeAg) production have been demonstrated in both infected patients who have seroconverted to anti-HBe and those with fulminant hepatitis B. A donated plasma sample was found to be positive for the hepatitis B surface antigen, but negative for both HBeAg and anti-HBe. The HBV DNA titer in the plasma was estimated to be 32 pg/ml, and circulating virus-like particles were observed by electron microscopy. The entire nucleotide sequence of the virus was determined and at least 7 nucleotides were found to be unique when compared with previously reported sequences. These nucleotides created no termination codon in the precore/core, pol, preS/S and HBx open reading frames. The deduced amino acid substitutions were 28 Arg--Gln, 94 His--Tyr, 131 Val--Ile and 132 Phe--Tyr of HBx and 715 Met--Val and 789 Asp--Asn of pol. Furthermore, the precore and core/pregenome promoter contained altered 1764 A, 1766 T and 1768 A. Therefore, mutations in regions other than the precore open reading frame can cause defective HBeAg production.
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PMID:Mutations in the transcriptional regulatory region of the precore and core/pregenome of a hepatitis B virus with defective HBeAg production. 785 32

Hepatitis B virus (HBV) DNA was extracted from sera of six carriers with hepatitis B e antigen as well as antibody to hepatitis B surface antigen and sequenced within the pre-S regions and the S gene. HBV DNA clones from five of these carriers had point mutations in the S gene, resulting in conversion from Ile-126 or Thr-126 of the wild-type virus to Ser-126 or Asn-126 in three carriers and conversion from Gly-145 to Arg-145 in three of them; clones with Asn-126 or Arg-145 were found in one carrier. All 12 clones from the other carrier had an insertion of 24 bp encoding an additional eight amino acids between Thr-123 and Cys-124. In addition, all or at least some of the HBV DNA clones from these carriers had in-phase deletions in the 5' terminus of the pre-S2 region. These results indicate that HBV escape mutants with mutations in the S gene affecting the expression of group-specific determinants would survive in some carriers after they seroconvert to antibody against surface antigen. Carriers with HBV escape mutants may transmit HBV either by donation of blood units without detectable surface antigen or through community-acquired infection, which would hardly be prevented by current hepatitis B immuneglobulin or vaccines.
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PMID:Naturally occurring escape mutants of hepatitis B virus with various mutations in the S gene in carriers seropositive for antibody to hepatitis B surface antigen. 813 44


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