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U Ragnarsson

Publications and source records attributed to U Ragnarsson.

At least 55 records · Page 3Linked to original sources
PubMed1985

Synthesis, antidiuretic and pressor activities of [arginine4]arginine-vasopressin and two related analogues.

Using well-established solid-phase techniques, three new analogues of arginine-vasopressin (AVP) were synthesized. In these the glutamine residue in position 4 was replaced with an additional arginine. The new analogues were: [Arginine4]arginine-vasopressin ([Arg4]AVP), [2-thiopropionic acid1,arginine4]arginine-vasopressin (d[Arg4]AVP) and [1-thiocyclohexaneacetic acid1,arginine4]arginine-vasopressin (d(CH2)5[Arg4]AVP). [Arg4]AVP showed about the same antidiuretic activity as AVP but had only about 40% of its pressor activity. Unexpectedly, deamination caused a drop in the antidiuretic activity to about 50%. d(CH2)5[Arg4]AVP had practically negligible antidiuretic and low pressor effects.

Amino Acid Sequence↗
PubMed1983

Tripeptidyl aminopeptidase in the extralysosomal fraction of rat liver.

An enzyme which removes tripeptides from the free, NH2-terminal end of oligopeptides has been detected in the extralysosomal fraction of rat liver. The enzyme was partially purified by Sepharose CL-4B and DEAE-cellulose chromatography. The pH optimum was in the neutral range and the apparent native molecular weight was above 10(6), as judged by the Sepharose chromatography. The enzyme cleaved the phosphopeptide Gly-Val-Leu-Arg-Arg-Ala-Ser(P)-Val-Ala (I), first at the Leu-Arg bond and then at the Ala-Ser(P) bond. The cleavage of the former bond was inhibited by Arg-Arg-Ala-Ser(P)-Val-Ala (II), which indicated that both bonds were cleaved by the same enzyme. Km for II was 0.01 mM at pH 6.5-7.5. Val-Leu-Arg-Arg-Ala-Ser(P)-Val-Ala (III) and Leu - Arg - Arg - Ala - Ser(P)-Val-Ala were poor substrates. III was, however, found to be an efficient inhibitor. The Ala-Ser(P) bond of Arg-Arg-Ala-Ser(P)-Val (IV) was cleaved at the same rate as that of II. The enzyme was active also with the unphosphorylated peptides corresponding to II and IV and tolerated the substitution of lysine for the NH2-terminal arginine of the latter peptide. Substitution of guanidovaleric acid for the NH2-terminal arginine of IV and of guanidovaleric acid or epsilon-amino-hexanoic acid for the NH2-terminal arginine of unphosphorylated IV reduced the rate of hydrolysis to insignificant levels, demonstrating the importance of a free NH2 terminus. The results provide evidence of a unique tripeptidyl aminopeptidase.

Aminopeptidases↗
PubMed1983

Structural requirements for microvascular permeability-increasing ability of peptides. Studies on analogues of a fibrinogen pentapeptide fragment.

A pentapeptide, Ala-Arg-Pro-Ala-Lys, liberated from fibrinogen during plasmin-mediated fibrinolysis, was shown earlier to increase microvascular permeability in rat and human skin. Eighteen new analogues have now been synthesized in addition to the 15 previously prepared and examined for their effect on permeability. The old concept that a tetrapeptide with basic amino acids at both ends and a proline residue adjacent to the N-terminal amino acid is essential for high activity on permeability, has now been challenged. The results obtained with several of the new analogues strengthen this concept. More interestingly, however, the third amino acid, which was found in earlier studies to be less sensitive to exchange, has now been deleted as well as duplicated with only a modest loss of activity of the peptide. The chirality of the C-terminal amino acid, most surprisingly, does not seem to be crucial for peptide activity. Slightly superpotent analogues were obtained on amidation of the C-terminus. In addition, a few naturally occurring peptides, namely tuftsin, substance P, neurotensin and bradykinin, the amino acid sequences of which all exhibit characteristic features of some of our active peptide analogues were investigated in the same test system. Tuftsin displayed a potency equal to that of the pentapeptide. The other three peptides were all highly superpotent in this assay system.

Animals↗
PubMed1983

Synthesis and antiviral activity of distamycin A analogues: substitutions on the different pyrrole nitrogens and in the amidine function.

Several new analogues of the antiviral antibiotic distamycin A were synthesized and assayed for their effects on influenza and herpes simplex virus. The new compounds 5b-j (R1-3 = H, CH3, and C2H5, R4,5 = H and CH3) were obtained via stepwise prepared formylated trimeric benzyl 4-aminopyrrole-2-carboxylates 3a-h, which after catalytic hydrogenolysis were coupled as N-succinimidyl esters directly with the proper beta-aminopropionamidine, unsubstituted or substituted with one or two methyl groups in the amidine function. Most of the new analogues did not exhibit significant effects on the viruses studied, but three compounds (5f-h) displayed activity on herpes virus as demonstrated in plaque formation and virus yield assays. Elevated cytotoxicity was simultaneously observed for 5g and 5h. For compound 5f, a partial separation of antiherpes activity and cytotoxicity was accomplished. The differences in antiherpes activity did not correspond to the differences in the inhibition of herpes virus DNA polymerase.

Animals↗
PubMed1983

Solid-phase synthesis of the non-calcium-binding loop of cod allergen M. Direct evidence of the reactivity of the amino-terminal segment.

The synthesis of the non-calcium-binding AB loop of the assembly 13-32 of cod Allergen M (Mr 2122.1) was accomplished by solid-phase peptide synthesis. This peptide and the previously synthesized ones [12, 13, 14] have significant amino acid sequence homology. The synthetic crude preparation was obtained at relatively high recovery and purity. Further purification on a Bio-Gel P-2 column and a reversed-phase high-performance liquid chromatography column improved the grade of homogeneity, as demonstrated by high-voltage electrophoresis, end-terminal analysis, and amino acid composition. The peptide could, although to a much weaker extent than the intact Allergen M, directly bind IgE antibodies from the sera of cod-allergic individuals. At identical molar concentrations, a ratio of 1:6 for the in vitro reactivity of the peptide relative to the intact Allergen M was obtained. A similar reactivity was shown in the in vivo system used. The peptide also reacted with rabbit anti-Allergen M antibodies in rocket immunoelectrophoresis. The peptide appears to function as a divalent molecule in its primary interaction with antibodies.

Allergens↗
PubMed1981

A comparative structural study of apamin and related bee venom peptides.

Secondary structure analysis of apamin, mast cell degranulating peptide, tertiapin and secapin has been attempted, based on parameters produced by Levitt (Biochemistry (1978) 17, 4277--4285). The structural model, recently advanced for apamin, based on Chou and Fasman's parameters was confirmed. The predicted structure for mast cell degranulating peptide is almost spherical with the eight positive centres evenly distributed over the surface. On the basis of this analysis and related spectroscopic evidence, it is suggested that these four peptides share a common folding pattern, which is centered on a beta-turn covalently linked to an alpha-helical segment by two disulphide links (one disulphide link in the case of secapin). It is further suggested that apamin, mast cell degranulating peptide and tertiapin form a single molecular class.

Amino Acid Sequence↗
PubMed1981

Allergenic synthetic peptide corresponding to the second calcium-binding loop of cod allergen M.

A peptide with the sequence of the second calcium-binding loop (EF loop) of cod Allergen M was synthesized by automatic solid-phase technique. The synthetic peptide corresponded to residues 88-103 of the known primary structure of Allergen M. The immunochemical reactivity of this loop, previously demonstrated for the overlapping enzymic fragments, was confirmed by using the synthetic preparation. The purified hexadecapeptide was shown to bind specifically to reaginic IgE from sera of cod-allergic individuals, in both in vivo and in vitro tests systems. It could also bind rabbit anti-Allergen M, as shown by rocket line immunoelectrophoresis and quantitative precipitation inhibition techniques. The findings emphasized that the immunological reactivity of the synthetic peptide (88-103) was compatible with a monovalent haptenic function: blocking and not eliciting allergic reactions.

Allergens↗
PubMed1981

Potentiation of bradykinin with synthetic peptides on guinea pig ileum.

Potentiation of the activity of bradykinin on the isolated guinea pig ileum was studied using a designed test system with the synthetic peptides Leu-Val-Glu-Ser-Ser-Lys, Thr-Pro-Val-Ser-Glu-Lys, derivatives of the former coupled to the N- and C-terminals of bradykinin and two peptides with phenylalanine substituted with its isomer L-3-amino-3-phenylpropanoic acid in the 5- and 5,8-positions in bradykinin respectively. On average, two times potentiation effects were obtained at 10-6 to 10-8 M concentrations of the peptides. After elimination of the basic lysine no potentiation occurred with synthetic Leu-Val-Glu-Ser-Ser. With the [beta Phe5,8]-bradykinin a mixed sensitizing/potentiating effect was observed, suggesting that a separation of the two effects may be difficult with an intact receptor structure of this kind. This peptide was not hydrolyzed by carboxypeptidase B or chymotrypsin.

Animals↗
PubMed1980

Phosphopeptide substrates of a phosphoprotein phosphatase from rat liver.

The substrate specificity of a preparation of phosphoprotein phosphatase (Mr = 32 000) from rat liver was investigated. Phosphopeptides based on the structure Leu-Arg-Arg-Ala-Ser(P)-Val-Ala-Glx-Leu and Ala-Arg-Thr-Lys-Arg-Ser-Gly-Ser(P)-Val-Tyr-Glu-Pro-Leu-Lys were used. These phosphopeptides correspond to the phosphorylation sites of rat liver pyruvate kinase (type L) and the beta subunit of rabbit muscle phosphorylase b kinase, respectively. A decrease in the apparent Km values and a concomitant increase in Vmax values was observed when the number of amino acyl residues after the phosphoseryl residue in the respective phosphopeptides were increased from 2 to 4, 5, or 6. Most of the phosphopeptides investigated generally showed apparent Km values higher than the values obtained with phosphopyruvate kinase. Ala-Ser(P)-Val-Ala and Gly-Ser(P)-Val-Tyr appeared to be the shortest phosphopeptides that could be dephosphorylated rapidly. These findings support the hypothesis that a small part of the phosphoprotein may be sufficient to fulfill the minimal requirements for its dephosphorylation.

Amino Acid Sequence↗
PubMed1980

Structure-activity studies on synthetic analogs to vasoactive peptides derived from human fibrinogen.

Counterparts to two vasoactive peptides previously isolated from fibrin(ogen) degraded by plasmin (EC 3.4.21.7) were synthesized by the solid phase procedure. The synthetic undecapeptide (Ser-Gln-Leu-Gln-Lys-Val-Pro-Pro-Glu-Trp-Lys) was isolated in a homogeneous state by chromatography on Sephadex G-25 and DEAE-Sepharose CL-6B and the pentapeptide (Ala-Arg-Pro-Ala-Lys) by chromatography on BioGel P-6 and column zone electrophoresis. The effect of these two peptides and of fifteen analogs to the pentapeptide on microvascular permeability in rat skin was investigated. The two synthetic counterparts were as potent as the natural peptides. With respect to the analogs, the influence of different functional groups was first studied. This was followed by attempts to minimize the active structure, induce or relieve rigidity of the peptide back-bone or otherwise accomplish modifications by a change in chirality at critical positions. Our results show that the tetrapeptide Arg-Pro-Ala-Lys has the same effect on microvascular permeability as the pentapeptide in the assay system used. Basic amino acids at both ends, as well as a proline residue adjacent to the N-terminal amino acid appear important for full or essentially full activity. On the other hand, substitution of the Ala at position 4 with several other amino acids did not result in a significant loss in biological potency.

Capillary Permeability↗