Dissociation of histamine releasing activity and T -cell reactivity of allergen conjugated with synthetic polymer.
Explore the source record for details and available documents.
Allergens↗
Biomedical subjects
S M Andreev
Publications and source records attributed to S M Andreev.
Targeting of liposomes to HIV-1-infected cells by peptides derived from the CD4 receptor.
Liposomes can be targeted to HIV-infected cells by either reconstituting transmembrane CD4 in the membrane or covalently coupling soluble CD4 to modified lipids. We investigated whether synthetic peptides could be used as ligands for targeting liposomes. A synthetic peptide from the complementarity determining region 2 (CDR-2)-like domain of CD4 could bind specifically to HIV-infected cells and mediate the binding of peptide-coupled liposomes to these cells. A peptide from the CDR-3-like domain of CD4 inhibited HIV-induced syncytia formation, but failed to target liposomes to infected cells. This apparent discrepancy may be due to the requirement for a conformational change in the CD4 receptor for the CDR-3 region to interact with the HIV envelope protein. Our results demonstrate the feasibility of using synthetic peptides to target liposomes containing antiviral drugs to HIV-infected cells.
Amino Acid Sequence↗
[Modification of the functional activity of neutrophils by a synthetic peptide from the V3-loop of the HIV envelope protein gp120].
Explore the source record for details and available documents.
Antibody-Dependent Cell Cytotoxicity↗
[Fusion of negatively-charged liposomes under the effect of peptides from the N-terminal fragment of the HIV-1 transmembrane protein].
The effect of a series of synthetic peptides mimicking the N-terminus of HIV transmembrane glycoprotein (gp41) on fusion of negatively charged liposomes consisting of phosphatidylcholine, phosphatidylethanolamine and cardiolipin at a 2:3:5 molar ratio, respectively, has been studied. Peptides P514 and P385 (residue 517-538), lysine and arginine at the C-terminus, respectively, with the amino acid sequence completely corresponding to the N-terminus of gp41 displayed the highest fusogenic activity. The extent of fusion was significantly increased at mild acidic pH (6.0). Acidification particularly influenced the fusogenic activity of P514. Modification of the N- and C-termini of fusion-active peptides by proteins and synthetic polymers blocked the fusion activity. The fusogenic properties of peptides depended on the chain length: P411 consisting of nine hydrophobic amino acid residues had no fusogenic activity, while P415, an 11-member peptide, effectively fused liposomes. The fluorescent probe ANS was used to monitor the hydrophobicity of these peptides. The hydrophobicity of P514 increased appreciably with a change in pH from 6.0 to 7.5. Peptides P514 and P385 induced the leakage of the aqueous contents from liposomes at neutral pH and caused a small, but detectable leakage at acidic pH. Structural and molecular factors influencing the peptide-induced liposome fusion are discussed.
Amino Acid Sequence↗
[Identification of immunoreactive epitopes in proteins coded by gag, env, and pol genes of the type I human T-lymphotropic virus (HTLV-I) using synthetic peptides].
Reactivity of 26 synthetic peptides that comprise 12 to 26 amino acid residues corresponding to segments of the gag p19, env gp46, and pol proteins of human T-lymphotropic virus type I toward 31 positive sera was studied using enzyme-linked immunosorbent assay. Specific reactivity with high titers of antibodies (presented in reciprocal dilution values) was detected for the synthetic peptides corresponding to fragments 110-130 and 100-130 (titers up to 4050) of p19, 174-197 (up to 800), 186-201 (up to 4050), 191-215 (up to 1350), 242-257 (up to 800), and 272-292 (up to 450) of gp46. Immunoreactivity of seven peptides, fragments of pol-proteins, was weak. New linear epitopes in the regions 145-158, 272-277, and 292-300 of gp46 were detected. In addition, location of the known linear epitopes in p19 and gp46 was refined on the basis of comparative study of overlapping peptides from these proteins.
Amino Acid Sequence↗
Inhibition of human immunodeficiency virus type 1 (HIV-1) penetration into target cells by synthetic peptides mimicking the N-terminus of the HIV-1 transmembrane glycoprotein.
To investigate the mechanism of action of the 22-amino-acid HIV fusion peptide on HIV infection, we studied its influence on virus adsorption and HIV-induced syncytium formation. The effect of the peptide preparations on the synthesis of viral antigens in HIV-infected cell cultures was determined by antigen capture assay, and the inhibition of proviral DNA synthesis was detected by hybridization with a HIV-specific oligonucleotide probe after PCR amplification. Fusion peptides inhibited HIV-induced syncytium formation and antigen production in lytic infected cells, and this effect was increased in conjugation with bovine serum albumin or with synthetic net-charged polymer by its C-terminus. The association of peptide with carrier by N-terminus, or with positive-charged polymer or gelatin completely abolished its effect on HIV infection. No peptide preparations influenced HIV-1 chronically infected cells. Because peptide preparations blocked the HIV-specific DNA synthesis 2 hr after infection without influencing virus adsorption and reverse transcription, we concluded that the block of infection occurred during the penetration of virions through the cell membrane. On the basis of results obtained we propose that our peptide preparations could be used for anti-HIV chemotherapy. The possibility of the existence of receptors for gp41 N-terminal region on target cell membrane is discussed.
Amino Acid Sequence↗
[A synthetic peptide-based immunoenzyme test system for the joint detection of human retrovirus (HTLV-1 and HIV-1) antibodies].
The study was made to develop an immunodiagnostic test system based on synthetic peptides able to detect in the same assay the total concentration of heterospecific antibodies against human retroviruses HTLV-1 and HIV-1. Three panels of reference-sera contained antibodies to HTLV-1 (70 specimens), HIV-1 (50 and 16 specimens) and 4 synthetic peptides corresponding to protein fragments p19 gag and gp46 env HTLV-1, gp120 and gp41 env HIV-1. Immune reactivity of the peptides with reference sera was measured in the immunoassay. It is established that relevant peptides mimic immunodominant B-epitopes of structural proteins HTLV-1 and HIV-1 and are recognized specifically by relevant antiviral antibodies. The enzyme immunoassay test system has been designed using a peptide combination in a single antigen complex. The system showed high diagnostic sensitivity.
Antibodies, Heterophile↗
[Effect of synthetic fragments of immunodominant regions of HIV viral proteins on the oxygen metabolism of human neutrophils].
Influence of synthetic peptides identical to fragments of natural human immunodeficiency virus (HIV) glycoproteins gp 120 and gp 41, on luminol-enhanced chemiluminescence (CL) of human neutrophils has been studied. It was established that some of peptide analogs of gp 120 and gp 41 immunodominant regions are able to suppress spontaneous CL: but when being used with dimethylsulfoxide they dramatically stimulate it and deteriorate opsonized zymosan-induced CL. Conclusions about the necessity of possible side effects considering during use of peptide vaccines against HIV have been made. It is also possible to explain some neutrophil dysfunction in HIV infected subjects as the result of HIV glycoproteins direct influence on this cells.
Acquired Immunodeficiency Syndrome↗
Investigation of human immunodeficiency virus fusion peptides. Analysis of interrelations between their structure and function.
The N-terminal region of the human immunodeficiency virus type 1 (HIV-1) gp41 appears to be involved in virus-cell membrane fusion. To study the influence of fusion domain structure on gp41 interaction with artificial lipid membranes, two families of peptides were synthesized. The peptides of the first family starting from the C-terminal Gly-532 of gp160 (BRU isolate) were assembled in a stepwise manner to N-terminus of gp41(Ala-517). These hydrophobic peptides, containing 10-16 amino acid residues (a.a.), were able to form channel-like current fluctuation through planar lipid membranes, and the longest 15-16 a.a. peptides lysed the liposomes. Peptides of the second family beginning from the C-terminal Arg-538 and continuing to Val-510 contained several hydrophilic amino acid residues. These 15-22 a.a. peptides also increased the conductance of planar lipid bilayers and lysed liposomes. The degree of liposome lysis depended upon peptide length and concentration. The attachment of gp120 C-terminal amino acid or peptides to N-terminus of 517-538 peptide resulted in complete loss of activity. The effects of the second family of peptides on membranes were reduced to a great extent at acidic pH. The conjugation of 22 a.a. Lys peptide with bovine serum albumin decreased its lytic activity. The circular dichroism study of these peptides revealed alpha-helix configuration in hydrophobic and aqueous media only for deca- and longer peptides. The electron microscopy of 22 a.a. peptide performed in the aqueous medium showed large spherical aggregates about 0.5-0.7 micron in diameter consisting of long filaments approximately 5 nm in diameter. Other tested peptides could generate only short strings. Thus, the effects of fusion peptides on lipid membranes depends on their sequence and length, secondary and tertiary structures, and freedom of their N-terminus.
Amino Acid Sequence↗
[Peptides from the principal neutralizing and CD4-binding domain: similar immunoreactive properties and structure pattern].
The human immunodeficiency virus (HIV) proteins gp120 and gp41 are the principal immune target in HIV infection. One of the most important trends in the study of AIDS is linked to the mapping of sites involving in the binding to the cell receptor CD4 and in the induction of virus-neutralizing antibodies (VNA). Recent studies have revealed that gp120 as the major domain contains inducing type-specific BNA (PND) and a binding region with CD4 (CD4-BR). PND is located in the hypervariable loop of gp120 (residues 301-336 for a BRU strain), and CD4-BR is in the conservation area (residues 410-450). By using the synthetic fragments from these areas (BRU and MN strains) and HIV-infected persons' sera, the authors established that the immune response to PND and CD4-BR is somewhat interrelated: there is a synchronized response of HIV antibodies to peptides from the two regions in ELISA (r = 0.82). For analysis of this phenomenon, experiments with cross-linked immunoreactivity of rabbit antisera to peptides from PND and CD4-BR with homologous and heterologous peptides were performed by applying three control peptides from HIV and hepatitis B virus. It has been found that there is a cross reactivity between rabbit anti-PND (MN, BRU) and anti-CD4-BR abs. Peptide homological analysis revealed common structural elements for PND and CD4-BR despite significant differences in their proposed functions. There is a large amount of positively charged aa within both PND and CD4-BR which may be involved in gp120-CD4 interaction. Acetylation of Lys residues resulted in complete loss of peptide reactivity.
Acquired Immunodeficiency Syndrome↗
Analysis of the fine structure of the antigenic determinants of the transmembrane protein in the HIV coat with chemically modified synthetic peptides.
The amino acids involved in IgG reactivity to four HIV-1 gp41 overlapping synthetic peptides from the sequence 584-624 have been determined by a method based on the chemical modification of trifunctional amino acids, especially the acetylation of the amino groups of the lysine residues at pH 8-9. The reactivities of the sera from HIV-infected individuals and gp41-specific human Mab were studied with the overlapping peptides and their modified forms in indirect and competitive ELISA. Peptides 584-602 and 609-624 (CN-185) reacted with 88% of HIV-positive sera; the highest diagnostic significance (100%) was found with peptides 584-611 (AS-551) and 603-624 (CN-191). Acetylation resulted in a 10%-15% decrease in peptide reactivity. Moreover the concentration at which 50% inhibition occurred was 1.5 x 10(-6) M for unmodified AS-551 compared with 1.5 x 10(-5) M for the modified peptide. Circular dichroism spectra showed that acetylation did not alter the conformation of these peptides. Coupling of peptide AS-551 to a protein carrier at pH 6.5-7.0 did not affect the immunoreactivity of this peptide. Mab against human gp41 reacted with peptide 603-624 (CN-191). The concentration of this peptide necessary for 50% inhibition of Mab binding was 5.2 x 10(-6) M. It is concluded from the epitope mapping of the Mab that the antigenic determinant lies within the 603-609 fragment. Lys-608 appears to play a crucial role in the interaction with human HIVc-Mab.
Amino Acid Sequence↗
[Cellular immunity function in HIV-1-infected persons].
The data on the state of cell-mediated immunity in patients with AIDS-related complex are presented. The synthetic peptide of membrane protein gp120 of HIV-1 was shown to inhibit leukocyte adhesion in persons under examination, as well as to have the tendency towards inhibiting the chemotaxis of migratory cells. The maximum effect was achieved at a peptide concentration of 10(-6) M. The data obtained in this investigation suggest the presence of specific cell-mediated sensitization to the fragment of protein gp120, detected by the adhesion inhibition test with the use of spectrophotometric techniques and the capillary evaluation of the chemotaxis of migrating cells, in patients with AIDS-related complex.
AIDS-Related Complex↗
Interaction of human immunodeficiency virus (HIV-1) fusion peptides with artificial lipid membranes.
The interaction of 11 overlapping synthetic peptides corresponding to N-terminal segment of HIV transmembrane glycoprotein gp41 (fusion domain) with artificial lipid membranes has been studied. For this purpose the increase of a bilayer lipid membrane (BLM) conductivity and the changes in ESR spectra of spin-labelled liposomes were registrated. Peptide fragment 523-532 gp160 (BRU strain) had the critical length with regard to channel-forming activity on BLM. The degree of such membranotropic action increased simultaneously with the growth of peptide length and the temperature in the cell. Peptides 518-532 and 517-532 lysed TEMPOcholine-containing liposomes at 37 degrees C. The significance of observed effects for explanation of the mechanism of HIV-induced membrane fusion is discussed.
Amino Acid Sequence↗
Prospects for the use of synthetic antigens in immunodiagnosis.
Methods for the localization and prediction of protein antigenic determinants are described, and the diagnostic potential of synthetic peptide antigens in cases of HIV, hepatitis B, and influenza is demonstrated. Attention is concentrated on the principles governing the creation and application of artificial diagnostic preparations.
Amino Acid Sequence↗
The use of synthetic peptides in the diagnosis of HIV infections.
The antigenic structure of HIV proteins was analyzed semiempirically. Peptides mimicking fragments of the main structural HIV-1 proteins (p17, p24, gp41, and gp120) were selected and synthesized, with account taken of the level of conservation of various HIV genome fragments. The synthesized peptides were then subjected to immunological study with human sera in an enzyme-linked immunosorbent assay (ELISA). Peptides from two regions were found to be particularly immunoreactive with sera from HIV-1 infected persons: the C-terminal end of gp120 and a sequence approximately sixty to eighty amino acids in from the N-terminus of gp41. In fact, more than 96% of HIV-1 positive sera reacted with peptide 495-516 of gp120 (SP-III), peptide 584-602 of gp41 (LS-19), and peptide 601-616 of gp41 (SP-15). Additionally, twelve out of twelve serum samples from Ugandans infected with HIV-1 reacted with both SP-III (from HTLV-III) and SP-29 (gp41, 598-609; from the LAV-ELI isolate), suggesting that these immunodominant sites are useful diagnostically irrespective of the infecting isolates. HIV-2 peptides were also synthesized, and immunoreactivity and cross-reactivity examined. Only two peptides (581-603 of gp32 and 592-605 of gp32) reacted with all of the six HIV-2 positive sera tested. These peptides did not react with HIV-1 positive sera or control sera from healthy blood donors.(ABSTRACT TRUNCATED AT 250 WORDS)
Amino Acid Sequence↗
[Study of the antigenic structure of hepatitis B virus proteins. I. Synthesis of pre-S fragments of hepatitis B virus proteins and their immunogenicity].
Fragments of hepatitis B virus envelope proteins corresponding to the parts of the pre-S domain were synthesised and immobilized on the carriers with low own immunogenicity. The highest stimulation of the antibody production was observed for the antigens immobilized on microspherical carriers or gelatin modified by H-Gly-Tyr-OH. Among peptides used for immunization, pre-S fragment 134-144, conjugated with microspherical carrier, proved to be the most active.
Amino Acid Sequence↗
[Localization of ligand-receptor sites of proteins].
Explore the source record for details and available documents.
Amino Acid Sequence↗
[Excitatory effect of tuftsin tetrapeptide on the activity of white rats].
Studies on male white rats have shown that tuftsin (trelys-pro-arg) enhances the locomotion in animals as disclosed by a series of the behavioral tests. The effect is dose-dependent: a dose of 50 microgram/kg did not change any of the test parameters, while that of 150 microgram/kg induced a short-term elevation of locomotion measured with an "Animeks". Administration of tuftsin in a dose of 300 microgram/kg led to the enhancement of the animals' locomotion as measured with the "Animeks", to the increased "open field" running time and to the reduced latent period of the reaction during the training in a T-shaped maze. Also, this dose of the peptide relaxed the reactions associated with fear. It is assumed that the effects observed are consequent on the stimulant action of tuftsin on the body of white rats.
Animals↗