Biomedical peptides, proteins & nucleic acids : structure, synthesis & biological activity最新文献

{"title":"Effect of serum amyloid A, HDL-apolipoprotein, on endothelial cell proliferation. Implication of an enigmatic protein to atherosclerosis.","authors":"R Shainkin-Kestenbaum,&nbsp;S Zimlichman,&nbsp;M Lis,&nbsp;C Lidor,&nbsp;M Pomerantz,&nbsp;A Knyszynski,&nbsp;L Preciado-Patt,&nbsp;M Fridkin","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The possible contribution of apo-HDL serum amyloid A (SAA) to the protective effect of HDL against atherosclerosis was studied by evaluating its effect on bovine aortic endothelial cell (BAEC) proliferation. Our results suggest that human SAA, both purified and recombinant, in concentrations relevant to mild acute phase events, significantly inhibit endothelial cell proliferation in a dose-dependent manner (e.g., 50 micrograms/ml causes approximately 88% inhibition; p < 0.001). This inhibition was attenuated by addition of fibroblast growth factor (FGF), which antagonized the SAA-mediated effect. As levels of TNF may be highly elevated during the acute phase response, its effect on BAEC proliferation was evaluated and found, at concentrations of > 1 pg/ml, to be substantially inhibitory Co-incubation of cells with both SAA and TNF was inhibitory, albeit neither additive nor synergistic. FGF antagonized the effect of both proteins. Amyloidic deposit (AA, i.e. SAA 1-76), derived from pathological proteolysis of SAA, practically retains the inhibitory activity (e.g. 50 micrograms/ml causes approximately 66% inhibition; p < 0.001) but apparently lacks the regulatory site towards FGF. In contrast to the above inhibitory effect, synthetic SAA-related peptide corresponding to the sequence 29-33 of SAA enhances BAEC proliferation (50 micrograms/ml causes approximately 64% increase; p < 0.001). The present data, coupled with our previous observations in which SAA was found to induce endothelial PGI2 formation and to inhibit overproduction of PGI2 by TNF and LPS as well as platelet aggregation, may suggest that SAA contributes to the protective effect of HDL against atherosclerosis. This, by means of its modulatory effect on endothelial cell and platelet activation, primarily in the presence of other regulatory proteins. SAA-derived peptides may, potentially, be used as therapeutic agents in the treatment of atherosclerosis and cardiovascular diseases.</p>","PeriodicalId":8980,"journal":{"name":"Biomedical peptides, proteins & nucleic acids : structure, synthesis & biological activity","volume":"2 3","pages":"79-84"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20496139","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The search for inhibitors of interleukin-1 based on the sequence of interleukin-1 receptor antagonist.","authors":"Z Wieczorek,&nbsp;A Kluczyk,&nbsp;J J Slon-Usakiewicz,&nbsp;I Z Siemion","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>In order to find the low-molecular-weight interleukin-1 (IL-1) inhibitors, we synthesised a series of peptides, derived from three regions of interleukin-1 receptor antagonist (IL-1ra): N-terminal (residues 5-9), central (90-98) and C-terminal (143-148). The decision was based on the thorough analysis of structural and functional properties of IL-1 proteins and the resemblance of some fragments of IL-1ra to well-known immunomodulators, like thymopentin and tuftsin. The competition between our peptides and IL-1 were measured as the inhibition of IL-1 induced IL-2 production in LBRM/CTLL cell line system. All peptides presented some activity, although the most interesting results (when the range of activity and dose-dependence were taken into account) were obtained for tuftsin and peptide VTKFYF from the C-terminal part of IL-1ra.</p>","PeriodicalId":8980,"journal":{"name":"Biomedical peptides, proteins & nucleic acids : structure, synthesis & biological activity","volume":"2 4","pages":"123-9"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20496098","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of oligonucleotides labelled with 2,4-dinitrophenyl groups at thymidine sites.","authors":"A Davison,&nbsp;J McClean,&nbsp;M V Rao,&nbsp;T Brown","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A phosphoramidite has been produced for labelling oligonucleotides with DNP groups at thymidine sites during solid-phase synthesis. The dinitrophenylamino group is attached via a caproamidopropargyl group to the 5-position of uracil. A related DNP-labelling phosphoramidite has been synthesised where the propargyl group is replaced by propyl. Both phosphoramidites have been used to synthesises DNP-labelled oligonucleotides. A related DNP-labelled deoxyuridine triphosphate has also been synthesised. DNP labelled oligonucleotide probes are valuable in diagnostic applications for the antibody-based detection of DNA and RNA.</p>","PeriodicalId":8980,"journal":{"name":"Biomedical peptides, proteins & nucleic acids : structure, synthesis & biological activity","volume":"2 1","pages":"1-6"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20278005","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Synthesis of GnRH analogs having direct antitumor and low LH-releasing activity.","authors":"I Mezô,&nbsp;J Seprôdi,&nbsp;B Vincze,&nbsp;I Pályi,&nbsp;G Kéri,&nbsp;Z Vadász,&nbsp;G Tóth,&nbsp;M Kovács,&nbsp;M Koppán,&nbsp;J E Horváth,&nbsp;A Kálnay,&nbsp;I Teplán","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>New chicken I GnRH agonists and antagonists have been synthesized and tested for their biological activities. The common feature of these analogs was that the molecules had a beta-L-aspartyl residue inserted in position 6. The agonist bound to the pituitary still had low endocrinological activity. On the other hand, it exhibited direct antitumor effect in in vitro assays. The endocrinological activity of the antagonist was low; however, it showed potent, direct antitumor activity. These observations might lead to the development of new GnRH analogs with selective antitumor effect.</p>","PeriodicalId":8980,"journal":{"name":"Biomedical peptides, proteins & nucleic acids : structure, synthesis & biological activity","volume":"2 2","pages":"33-40"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20277434","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"1H NMR structural study of free and template-linked antigenic peptide representing the C-terminal region of the heavy chain of influenza virus hemagglutinin.","authors":"J A Wilce,&nbsp;W Zeng,&nbsp;K Rose,&nbsp;D J Craik,&nbsp;D C Jackson","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>A 12 kDa template-assembled molecule, incorporating four oxime-linked synthetic peptides representing residues 306-328 of influenza virus hemagglutinin (HA), has been analysed by 1H NMR spectroscopy. The molecule (referred to as the 'tetraoxime') is of interest because it has been shown to elicit a better immune response than the free, monomeric peptide not only in the production of antibodies crossreactive with HA but also in its ability to elicit CD4+ T helper cells. We describe here an NMR structural analysis of (i) the unlinked template molecule and (ii) the free peptide and show that their conformations are not affected upon assembly of the tetraoxime. Our results suggest that the increased immune response observed for the tetraoxime may be due to its greater size and valency compared to that of the free peptide rather than being due to any induced structural effects.</p>","PeriodicalId":8980,"journal":{"name":"Biomedical peptides, proteins & nucleic acids : structure, synthesis & biological activity","volume":"2 2","pages":"51-8"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20277437","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Antibody-mediated detection and physical properties of oligonucleotides labelled with multiple internal and terminal 2,4-dinitrophenyl groups.","authors":"J McClean,&nbsp;A Davison,&nbsp;M V Rao,&nbsp;T Brown","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>DNP-labelled phosphoramidites have been used to synthesis oligonucleotides with multiple DNP reporter groups. The antibody-mediated detection and the stability of duplexes formed by these labelled oligonucleotides have been studied. A DNP-labelled deoxyuridine triphosphate has also been used to enzymatically incorporate DNP-labels into DNA via the polymerase chain reaction. The use of DNP-labelled primers in the PCR has also been investigated.</p>","PeriodicalId":8980,"journal":{"name":"Biomedical peptides, proteins & nucleic acids : structure, synthesis & biological activity","volume":"2 1","pages":"7-12"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20278006","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"The stability and conformation of duplex DNA containing the novel anti-HIV drug ADRT.","authors":"N J Gibson,&nbsp;C M McKellar,&nbsp;T Brown","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The anti-HIV drug 4'-azidothymidine (ADRT) has been incorporated into DNA by the phosphoramidite method. The presence of the modified nucleotide was shown to have a minimal effect on duplex conformation and stability by CD spectroscopy and UV melting.</p>","PeriodicalId":8980,"journal":{"name":"Biomedical peptides, proteins & nucleic acids : structure, synthesis & biological activity","volume":"2 1","pages":"23-5"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20278009","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Binding kinetics and bioassay of RRE mRNA fragments to a peptide containing the recognition domain of HIV-1 Rev.","authors":"M L West,&nbsp;T E Ramsdale","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Surface plasmon resonance techniques have been used to examine the kinetics of binding for two RNA fragments to an RNA binding domain of HIV-1 REv. RBE3 RNA elicited an apparent dissociation constant (KD) of 121 nM while RREIIB41-79 RNA exhibited an apparent dissociation constant (KD) of 2.5 nM. The dissociation rates for both RNA fragments were comparable. However, the shorter sequence, RBE3, exhibited considerably slower association kinetics. A series of known inhibitors were assayed against these RNA' and the derived K1's were consistent with those reported in the literature, validating the method for routine inhibitor assays.</p>","PeriodicalId":8980,"journal":{"name":"Biomedical peptides, proteins & nucleic acids : structure, synthesis & biological activity","volume":"2 3","pages":"85-8"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20496095","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Recognition of pituitary adenylate cyclase-activating polypeptide/vasoactive intestinal polypeptide (PACAP/VIP) hybrids and related peptides by rat brain membranes.","authors":"E Ando,&nbsp;K Nokihara,&nbsp;S Naruse,&nbsp;V Wray","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>The binding to [125I]PACAP27 and adenylate cyclase activity have been investigated using rat brain membranes with substituted analogues of PACAP and VIP, including their hybrid peptides. Binding of [125I]PACAP27 was rapid, specific and reversible. Scatchard analysis revealed a single class of binding site, with a Kd = 457 +/- 117 pM, and a Bmax = 2.63 +/- 0.24 pmol.mg protein-1. Hybrids of PACAP, in which specific residues were substituted with the corresponding residues of VIP, and vice versa, as well as related analogues, were then tested for binding and adenylate cyclase activity. The results showed that N-terminal residues were important for recognition. In particular, multiple substituted analogues of PACAP by VIP, and vice versa, demonstrated that positions 4, 5 and 9 play a dominant role in the recognition of PACAP Type I receptor in rat brain membranes and account for the differences observed between PACAP and VIP. Substitutions in the C-terminal region at positions 24, 25 and 26 are not crucial for recognition specificity. PACAP-analogues provide evidence that positions 1 and 6 are essential for receptor recognition. The flexibility at position 21 also appears to play a role as substitution with Ala or Phe is tolerated, while Pro shows a significant loss both in binding affinity and adenylate cyclase activity.</p>","PeriodicalId":8980,"journal":{"name":"Biomedical peptides, proteins & nucleic acids : structure, synthesis & biological activity","volume":"2 2","pages":"41-6"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20277435","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}

{"title":"Affinity purification of a correctly folded fragment of synthetic HIV-1 mRNA using a HIV-1 Rev peptide-ligand.","authors":"D R Englebretsen,&nbsp;M J Scanlon,&nbsp;M L West","doi":"","DOIUrl":"","url":null,"abstract":"<p><p>Formation of a macromolecular complex between the RNA binding protein HIV-1 Rev and HIV-1 mRNA is an essential prerequisite for nuclear export and subsequent expression of HIV-1 mRNA. The arginine rich peptide TRQARRNRRRRWRARQR, corresponding to residues 34-50 of HIV-1 Rev, contains the mRNA binding motif. We prepared a thioether linked Rev34-50-cellulose conjugate to affinity purify a fragment of synthetic mRNA corresponding to the high affinity binding site for Rev. The correctly folded fraction of mRNA (27.5%) was isolated from a crude synthetic mixture.</p>","PeriodicalId":8980,"journal":{"name":"Biomedical peptides, proteins & nucleic acids : structure, synthesis & biological activity","volume":"2 2","pages":"47-50"},"PeriodicalIF":0.0,"publicationDate":"1996-01-01","publicationTypes":"Journal Article","fieldsOfStudy":null,"isOpenAccess":false,"openAccessPdf":"","citationCount":null,"resultStr":null,"platform":"Semanticscholar","paperid":"20277436","PeriodicalName":null,"FirstCategoryId":null,"ListUrlMain":null,"RegionNum":0,"RegionCategory":"","ArticlePicture":[],"TitleCN":null,"AbstractTextCN":null,"PMCID":"","EPubDate":null,"PubModel":null,"JCR":null,"JCRName":null,"Score":null,"Total":0}