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M Zaoral

Publications and source records attributed to M Zaoral.

At least 19 recordsLinked to original sources
PubMed2000

Non-sequential vasopressin peptides. Stereochemistry and biological activity.

Two cyclic disulfides of structure Cys-Tyr-Arg-Arg-Tyr-Cys-NH2 (1) and Cys-Tyr(Me)-Arg-Arg-Tyr(Me)-Cys-NH2 (2), two nonapeptide derivatives of 1 extended at the C-terminal with Pro-Arg-Gly-NH2 (3) or Pro-D-Arg-Gly-NH2 (4) and derivatives of 3 and 4 having Mpr in position 1, i.e. analogs (5) and (6), respectively, were synthesized, and their stereochemistry and biological activity were studied. All the peptides displayed low dose-dependent uterotonic activity in vitro and antidiuretic activity in vivo. None of the peptides increased the blood pressure of the experimental animals. Compounds 2, 4 and 6 showed a low inhibitory effect on AVP pressor activity; compound 6, in addition, displays a significant and long-lasting vasodepressor effect. NMR measurements indicated the existence of hydrogen bond between the amino acid residues in positions 2,5 and 3,4 of peptides 1 and 2, and side-chain interactions between amino acid residues in positions 2,3 and 4,5 of peptide 1. No such side-chain interactions were detected in peptide 2.

Amino Acid Sequence↗
PubMed1987

Blood-platelets-damaging activity of some synthetic Streptococcus peptidoglycan subunits and analogues.

A series of 25 synthetic subunits or analogues of streptococcal peptidoglycan was tested for their ability to damage rabbit blood platelets. The morphological changes of the platelets were studied on an ultrastructural level. Minimal subunit structure able to produce a complete lysis of the platelets was found to be muramyldipeptide (MDP). Comparable lysis of platelets was also caused by muramyltetrapeptide and MDP containing D-Ala instead of L-Ala. The lytic effect was dose-dependent and was exhibited rather after high doses of the substances used (up to 500 micrograms/ml). For the lytic reaction, the configuration of C3 and C4 in the muramyl residue of MDP was essential. Many substances produced only degranulation without lysis of the platelets and some of them did not influence the platelet ultrastructure at all. The paper presents some structure-to-function relationships of the compounds and shows that the platelet-damaging activity of peptidoglycan may be related to certain portions of the peptidoglycan molecule. This activity should be tested when the immunomodulatory substances derived from the bacterial peptidoglycan are searched for.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1987

Immunogenicity of a synthetic peptide corresponding to a portion of the heavy chain of H3N2 influenza virus haemagglutinin.

Rabbits were immunized with a synthetic octadecapeptide corresponding to the sequence ser-91 to leu-108 of the haemagglutinin heavy chain of H3N2 influenza A viruses. They developed antibodies reactive in solid-phase radioimmunoassay (SPRIA) with the peptide and with haemagglutinins of various H3N2 viruses but not of heterotypic H1N1 and H2N2 viruses. The antibodies were also non-reactive in the haemagglutination-inhibition or neutralization test. Influenza H3N2 virus replicated in the lungs of mice immunized with the peptide to the same extent as in the control mice. Of 27 human sera possessing anti-H3N2 activity or seven sera from rabbits immunized with either virions or haemagglutinins of various influenza A viruses, none was reactive with the peptide in SPRIA.

Antigen-Antibody Complex↗
PubMed1985

Vasopressin analogs with high and specific antidiuretic activity.

A systematic approach to structure-activity studies is described. Its application to the vasopressin field made possible the preparation of vasopressin analogs with very high and very specific antidiuretic activity, analogs with increased pressor specificity, and analogs with high agonistic-antagonistic properties.

Animals↗
PubMed1985

Biological activity of synthetic subunits of streptococcus peptidoglycan. III. Relationship of subunit and analogue structure to adjuvant activity in cell-mediated immunity.

Each of a series of synthetic peptidoglycan subunits and subunit analogues was injected in combination with streptococcus type M24 antigen extract. The substances tested were: (8a) N-acetylmuramyldipeptide (MDP) and the following derivatives thereof: MDP modified in positions C3 and C4, or with L-alanine substituted by L-2-aminobutyric acid or with the peptide chain prolonged (by three lysines or a polylysine); (b) some synthetically prepared peptides: a hexapeptide, a tridecapeptide and an octadecapeptide. Configurations in positions C3 and C4 were found essential for the adjuvant effect. Adjuvant activity, though somewhat lower than in MDP, was pronounced in the analogue containing the L-2-aminobutyryl residue. Surprisingly, potent adjuvant effect was displayed by the hexapeptide; prolongation of the peptidic chain was not effective. The use of a polymeric carrier for MDP increased the adjuvant effect. Contrary to expectation, streptococcal antigens used with immunoadjuvant materials showed that induced delayed hypersensitivity was type related.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1984

Inhibition of tumor growth in mice treated with synthetic muramyl dipeptide.

Treatment with synthetic MDP inhibited growth of transplantable, chemically induced tumors in syngeneic mice. The tumor-inhibitory effect was dependent on the schedule of MDP administration. Growth of SC transplants of a nonmetastasizing, MC-induced fibrosarcoma, MC11, was inhibited by local treatment with 200 micrograms and 1,000 micrograms MDP given SC 5-7 weeks before challenge. Treatment with lower (10 micrograms and 100 micrograms) doses of MDP and shorter (1-4 weeks) time intervals was not effective. Single doses of MDP (10-1,000 micrograms) 1-3 weeks after challenge had no effect. Growth of IV-inoculated, metastasizing AAT-induced hepatoma A was inhibited by IV injections of 20 micrograms MDP given 1 and 2 days prior to the challenge. Significant increases in the survival of hepatoma-bearing mice were observed only after injections of MDP incorporated in multilamellar liposomes.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1984

Purification of pepsins and cathepsin D by affinity chromatography on Sepharose 4B with an immobilized synthetic inhibitor.

Val-D-Leu-Pro-Phe-Phe-Val-D-Leu, a specific inhibitor of aspartate proteinases of the pepsin type, was synthesized. Its bonding to activated 6-aminohexanoic acid-Sepharose 4B afforded an affinity support suitable for the purification of human, porcine, and chicken pepsin, human gastricsin, and bovine cathepsin D. These enzymes bind to the support over the pH range 2-5 at 0-1.5 M concentration of NaCl. A buffer at pH greater than or equal to 6, low ionic strength, and containing 20% dioxane can serve as a general desorption agent. The proteinases were isolated from the crude extracts by a single-step procedure in a high degree of purity and in yields exceeding 70%; human pepsin, however, was not separated from human gastricsin. The support does not show any binding capacity for rat plasma renin at pH 7.4 and for some cysteine endopeptidases (cathepsin B, H, and L) at pH 3-5. The cathepsin D preparations isolated by affinity chromatography on the new support and on pepstatin-Sepharose were of the same degree of purity as evidenced by sodium dodecyl sulfate-polyacrylamide gel electrophoresis, N-terminal amino acid sequences, and specific activity.

Animals↗
PubMed1983

Biological activity of synthetic subunits of Streptococcus peptidoglycan. II. Relation of peptidoglycan subunits and analogues to fever effect and induction of tolerance.

A series of synthetic subunits and analogues of streptococcal peptidoglycan was prepared and used in fever and tolerance experiments on rabbits. The lengthening of the chain of the peptide moiety of peptidoglycan did not result in pyrogenic activity, except for hexapeptide. Attachment of the muramyl residue rendered the peptides pyrogenic. The activity of such materials varied in degree and was rather in an indirect relation to peptide chain length. A change in the configuration of C4-OH or C3-OR in the muramyl residue resulted in a profound decrease in pyrogenicity. No inhibitory effect of N-acetylmuramyl-D-alanyl-D-isoglutamine on muramyldipeptide (MDP) pyrogenicity could be demonstrated. Repeated administration of MDP resulted in the induction of tolerance to the pyrogenicity of this substance in rabbits. These animals were not tolerant to the pyrogenicity of peptidoglycan. Nontolerance was also observed in reciprocal experiments with these materials as well as in trials with hexapeptide and peptidoglycan given in either order. The data are consistent with the assumption that peptidoglycan contains more than one biologically active subunit. There is a structure-to-function relationship. The knowledge of the biological effects of the synthetic analogues is essential for the prospect of their use under model or human conditions.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1982

Stimulation of non-specific resistance and specific immune response against tumours in mice by synthetic muramyl dipeptide.

Synthetic MDP administered in an aqueous medium at relatively high doses stimulates non-specific and specific tumour immunity. Non-specific inhibition of tumour growth was observed in B10 mice injected with 1 mg of MDP 14 days before transplantation of 3-Mc-induced sarcoma cells. Muramyl dipeptide in an aqueous medium increases specific tumour immunity when injected in the dose of 1 mg per mouse together with irradiated tumour cells.

Acetylmuramyl-Alanyl-Isoglutamine↗
PubMed1981

Beta-Endorphin: synthesis and radioreceptor binding activity of Beta h-endorphin-(1-27) and its analogs.

Beta h-Endorphin-(1-27) (I), [Ac-Tyr1]-beta h-endorphin-(1-27) (II), [Gln8]-beta h-endorphin-(1-27) (III), and [Ac-Tyr1, Gln8]-beta h-endorphin-(1-27) (IV) were synthesized by the solid-phase method. The binding potency of I-IV to rat brain membrane preparations was measured by radioreceptor binding assay. The relative potencies were: beta h-endorphin, 100; I, 30; II, 0.04; III, 90; IV, 0.07.

Amino Acid Sequence↗
PubMed1979

Structure specificity of some immunoadjuvant synthetic glycopeptides.

The immunoadjuvant activity of muramyl dipeptide seems to be critically dependent on the type of substitution of the gamma-carboxyl group of the D-isoglutamine residue. Moreover the nonapeptide L-Ala-D-isoGlu-L-lys-D-Ala-(Gly)5-OME also shows a definite effect.

Adjuvants, Immunologic↗
PubMed1979

Biological activity of synthetic subunits of streptococcus peptidoglycan. I. Pyrogenic and thrombocytolytic activity.

The ability of some synthetically prepared analogues of Streptococcus peptidoglycan subunits (dipeptide, tetrapeptide, glycodipeptide and glycotetrapeptide) to cause fever in rabbits and lysis of rabbit blood platelets was studied. While di- and tetrapeptides did not exhibit these activities, glycodipeptides and glycotetrapeptides displayed pyrogenic and thrombocytolytic activities comparable with those of natural peptidoglycans.

Blood Platelets↗
PubMed1978

Ten-year experience with DDAVP in treatment of diabetes insipidus.

Thirty patients with central diabetes insipidus were treated with 1-deamino-9-D-arginine vasopressin (DDAVP) during the period of 3--10 years. DDAVP was applicated in 1--3 intranasal doses daily. The dosage varied between 7--42 microgram/24 h. The diuresis before the treatment ranged between 28,000--7,600 ml/24 h (mean 13,883 ml/24 h) and was decreased by DDAVP below 2000 ml/24 h in 21 patients (70%) and to 2000--4000 ml/24 h in 8 patients (26.6%). In a single case it was not possible to reduce the diuresis from 20,000 ml below 8,000 ml/24 h. Favourable properties of DDAVP: absence of reduction of potency, lack of important side-effects and prolonged action were not lost even in the course of the long term treatment. No harmful effects of DDAVP were noted. Blood count as well as renal function tests were not affected by the treatment. All the patients preferred DDAVP to their previous therapy.

Adult↗
PubMed1976

Specific antidiuretic effect of [Leu4, D-Arg8] vasotocin and [Mpr1, Leu4, D-Arg8] vasotocin. Comment on the idea of lipophilic properties and position 4.

[Leu4, D-Arg8] vasotocin (I) and [Mpr1, Leu4, D-Arg8] vasotocin (II) possess a considerable and very specific antidiuretic effect. In I, the change of configuration in position 8 caused an increase of the magnitude of the antidiuretic effect. In I, the change of configuration in position 8 caused by two orders and a decrease of the magnitude of the pressor effect by one order. I and II are the first vasotocin analogues reported to have a relatively high and specific antidiuretic effect.

Animals↗
PubMed1975

Circular-dichroic spectra of vasopressin analogues and their cyclic fragments.

The circular dichroic spectra of [Arg8]vasopressin, [Mpr1, Arg8]vasopressin, [Mpr1, D-Arg8]-vasopressin, pressinamide, deaminopressinamide, tocinamide, deaminotocinamide, [Leu4, D-Arg8]-vasotocin, [Mpr1, Leu4, D-Arg8]vasotocin and [Phe2, Lys8]vasopressin have been studied. All these substances showed a characteristic positive dichroic band at about 225 nm due to the presence of tyrosine in sequence position 2. The intensity of this band was affected by interactions between the tyrosine side-chain and other structural elements in the molecule, such as the Na-amino group, the side-chain of phenylalanine in position 3 and the linear C-terminal peptide. Analysis of the response of this band to structural modifications of the molecule and change in the solvent (particularly comparing neutral aqueous solutions with hexafluoroacetone solutions) allowed some conformational conclusions. The linear C-terminal tripeptide is probably situated over the cyclic portion of the molecule both in vasopressin and oxytocin substances. Its steric interaction with the tyrosine side-chain seems to be particularly efficient in molecules containing D-arginine in position 8. In the vasopressin series the stacking interaction of neighbouring aromatic amino acid residues furthermore limits the conformational freedom of the tyrosine side-chain and also probably distorts the dihedral angles of residues 1-3 in comparison with oxytocin. The interactions of phenylalanine and arginine with tyrosine relatively decrease the conformational effects of the primary amino group. Consequently the local conformation of vasopressin in the region of the tyrosine residue is more rigid and less sensitive to changes in medium than that of oxytocin. The circular dichroic spectra did not show any basic conformational differences in the backbone peptide chain of oxytocin and vasopressin substances. A weak negative disulphide band at about 290 nm could be observed in the spectra of both series of substances.

Arginine Vasopressin↗