[The effect of modified forms of vasopressin on the rat hemostatic system]. / Vliianie modifitsirovannykh form vazopressina na sistemu gemostaza krys.

The effect of modified forms of vasopressin (MFV) that do not possess hormonal activity on homeostasis in rats was studied. One of the major effects of vasopressin (AVP) and its analogs on the blood clotting system, changes in fibrinolytic activity (FA) and the activity of plasminogen activator (APA), depends on modifications of the amino acid sequence in the peptide molecule. The presence of glycinamide in the AVP molecule enhances FA and APA. AVP molecules without the glycinamide group exert a more marked influence on procoagulant activity in blood.

[Structural and functional analysis of the human immunodeficiency glycoprotein gp120 with homologous synthetic peptides]. / Strukturno-funktsional'nyi analiz glikoproteina gp120 virusa immunodefitsita cheloveka s pomoshch'iu sinteticheskikh peptidov, gomologichnykh ego strukture.

The purpose of the study was to identify sites of gp 120, which are responsible for CD4 binding and induce tumor necrosis factor-alpha (TNF-alpha) synthesis. Seven peptides were synthesized from gp 120. The peptides were studied in the following biological tests: binding to CD4 molecules of the Jurkat cell clones 3G6 and PBMC of healthy persons. There was TNF-alpha induction in healthy and HIV-positive individuals and its correlation was found with p24 antigenemia in HIV patients. The peptides 420-440, 426-452, 369-384, 255-272 bind to T-lymphocytic CD4 and induced TNF-alpha. The peptide 436-451 binds to CD4, but failed to induced TNF-alpha, which suggests that the latter may be used as a basis for HIV-infection vaccine.

The sequence 130-137 of human interferon-alpha 2 is involved in the competition of interferon, prothymosin alpha and cholera toxin B subunit for common receptors on human fibroblasts.

125I-labelled recombinant human interferon alpha 2 (rHuIFN-alpha 2) capable of high-affinity binding (Kd = 2.46 +/- 0.18 x 10(-10) M) with receptors expressed on mouse thymocytes was obtained. Prothymosin alpha (proTM-alpha) but not cholera toxin was found to compete with radiolabelled IFN-alpha 2 for binding to the same receptor (Ki = 3.68 +/- 0.21 x 10(-11) M). The synthetic peptide covering the sequence 130-137 of IFN-alpha 2 (authors' definition: alpha-peptoferon) was shown to have the capacity to displace the labelled IFN-alpha 2 from the IFN-alpha 2/receptor complex (Ki = 7.19 +/- 0.12 x 10(-11) M). It was shown that receptors of this type are localized in plasmatic membrane fraction. Using [125I]-alpha-peptoferon, specific and saturable binding was detected on human fibroblasts and the data fitted a single binding site. Scatchard analysis yielded a Kd of 9.63 +/- 0.17 x 10(-8) M. The binding was competitively inhibited by IFN-alpha 2 (the Ki value in competition assays was 1.37 +/- 0.12 x 10(-8) M), proTM-alpha(Ki = 2.2 +/- 0.2 x 10(-7) M) and cholera toxin B subunit (Ki = 5.5 +/- 0.2 x 10(-7)). The present study has demonstrated that the sequence 130-137 of HuIFN-alpha 2 is involved in the competition of HuIFN-alpha 2, proTM-alpha and cholera toxin B subunit for common receptors on human fibroblasts.

[Conformational analysis and hemolytic activity of immunoglobulin G fragment 285-292 and its analogs]. / Konformatsionnyi analiz i gemoliticheskaia aktivnost' fragmenta 285-292 immunoglobulina G i ego analogov.

Theoretical conformational analysis was carried out for the 285-292 fragment of human immunoglobulin G (His-Asn-Ala-Lys-Thr-Lys-Pro-Arg) and its analogues containing Arg, Glu, Gly, Lys, or Trp residue instead of the His residue in position 1. Spectropolarimetic investigation of these peptides showed the analogues to have different activities in the C1q-mediated erythrocytes hemolysis assay. Comparison of the low-energy structures sets of the compounds tested allowed to suggest a model of the "biological active" conformation for the peptide molecule in the course of the C1q complement component binding.

Nonapeptide corresponding to the sequence 27-35 of the mature human IL-2 efficiently competes with rIL-2 for binding to thymocyte receptors [corrected].

Previously it was shown [1] that amino acid substitutions at the region of the first alpha-helix of IL-2 specifically inactivate its reactivity with the intermediate-affinity receptor p70, and mutations in the fifth alpha-helix specifically inactivate the binding to the low-affinity receptor p55. We have synthesized the peptides corresponding to the putative binding site of IL-2 with the intermediate-affinity receptor p70 and found that the nonapeptide corresponding to the sequence 27-35 of the mature IL-2 [2] effectively competes with human rIL-2 for binding to thymocyte receptors. Two types of nonapeptide receptors were revealed: those with Kd1 = 1.84 x 10(-8) M and Kd2 = 1.6 x 10(-7) M. The rIL-2 provides a 100% inhibitory effect on the binding of the 125I-labeled nonapeptide to thymocyte receptors, Ki = 3.5 x 10(-8) M. Low immunoproliferative activity of the peptide allows one to recommend it as a specific antiproliferation drug, IL-2 inhibitor [corrected].

The octapeptide corresponding to the region of the highest homology between alpha-interferon and thymosin-alpha 1 effectively competes with both cytokines for common high-affinity receptors on murine thymocytes.

The octapeptide corresponding to human interferon-alpha 2 (Hu IFN-alpha 2) sequence 131-138 has high affinity to murine thymocyte receptors (Kd = 4.2 x 10(-12) M, about 700 receptors per cell). The peptide receptor binding is inhibited by both Hu rIFN-alpha 2 (Ki = 8.6 x 10(-10) M) and thymosin-alpha 1 (TM-alpha 1) (Ki = 3 x 10(-7) M) as well as by the octapeptide homologous to the TM-alpha 1 sequence 16-23 (Ki = 4.5 x 10(-7) M). The peptide from IFN-alpha 2 (131-138) activates murine thymocyte blast transformation at a concentration of 10(-11) M in the presence of 2.5 micrograms/ml of concanavalin A.

Comparative activity of memory-modulating neuropeptides before and after electric shock in white rats.

Neuropeptides are shown to exert a powerful influence on mnestic processes. They actively eliminate phenomena of electric-shock amnesia, the strongest agent here being arginine vasopressin, while derivatives of oxytocin, enkephalin, and melanostatin are active to a lesser degree. The selective effect on primary learning (ACTH4-7 and Leu-enkephalin) and on the consolidation and restoration of memory (vasopressin and oxytocin), and the presence of only antiamnestic properties (analog of the melanocyte-inhibiting factor) - all this suggests different mechanisms of action of these agents. Memory modulators act more strongly upon activated systems that are already prepared to receive the signal. A promising object for future study as a therapeutic antiamnestic factor is the long-term memory modulator arginine vasopressin.

[Comparative evaluation of memory-regulating neuropeptides before and after electric shock in albino rats]. / Sravnitel'naia aktivnost' neiropeptidov--moduliatorov pamiati do i posle élektroshokovykh vozdeistvii u belykh krys.

Antiamnestic properties of memory neuropeptide--modulators and their effect on learning were studied as well as consolidation of oligopeptide ACTH4-7, vasopressin, oxytocin, leu enkephalin and the melanocyte inhibiting factor. Effect of these neuropeptides on the rat higher nervous activity is bath strong and specific: ACTH4-7 and leu enkephalin speed up the primary learning whereas vasopressin and oxytocin improve long--term memory. Peptides are able to reverse retrograde as well as anterograde amnesia and to preserve previously formed habits from disturbance by electric shock. Vasopressin and the melanocyte inhibiting factor are the strongest antiamnestic factors.