Search results

1

New analogue of cyclolinopeptide B modified by amphiphilic residue of α-hydroxymethylmethionine.

100%

Witkowska R., Donigiewicz A., Zimecki M., Zabrocki J.

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vol. 51

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issue 1

67-72

EN

In order to evaluate the role and influence of the methionine residue on the biological activity of cyclolinopeptide B, an analogue with methionine residue in position 7 replaced by the amphiphilic (S)-a-hydroxymethylmethionine residue was synthesized. This peptide exhibits high immunosuppressive activity in the cellular, and to a lesser degree in the humoral immune response, comparable to that of CsA. In addition, the peptide was devoid of toxicity, even at high doses.

2

DALDA analogues containing α-hydroxymethylamino acids.

100%

Olma A., Chung N. N., Schiller P. W., Zabrocki J.

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2001

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vol. 48

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issue 4

1121-1124

EN

To evaluate the role of aromatic amino-acids residues, four analogues of the μ-selec-tive opioid peptide agonist DALDA (H-Tyr-D-Arg-Phe-Lys-NH2) containing the amphiphilic, α,α-disubstituted amino acid (R)- or (S)-α-hydroxymethyltyrosine (HmTyr) in position 1 and (R)- or (S)-α-hydroxymethylphenylalanine (HmPhe) in position 3 of the peptide sequence were synthesized. Only the [(R)-HmPhe3)]DALDA analogue displayed full agonistic activity in both the guinea pig ileum and the mouse vas deferens assays and turned out to be a δ receptor-selective opioid agonist.

3

A novel cis-peptide bond motif inducing β-turn type VI. The synthesis of enkephalin analogues modified with 4-aminopyroglutamic acid.

88%

Kaczmarek K., Kaleta M., Chung N. N., Schiller P. W., Zabrocki J.

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2001

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vol. 48

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issue 4

1159-1163

EN

A new pathway leading to a mixture of four isomers of 4-aminopyroglutamic acid is described. Michael type addition of Z-ΔAla-OMe to enolates prepared from acylaminomalonates, followed by hydrolysis and decarboxylation give protected 4-aminopyroglutamic acid with the 4-aminopyroglutamic acid with the cis:trans ratio approximately 3:2. This mixture was incorporated into Leu-enkephalin (position 2-3). After separation of peptides it appeared that all analogues were essentially inactive in guinea pig ileum and mouse vas deferens bioassays.

4

Stereochemistry of insect kinin tetrazole analogues and their diuretic activity in crickets.

88%

Nachman R. J., Coast G. M., Kaczmarek K., Williams H. J., Zabrocki J.

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vol. 51

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issue 1

121-127

EN

Insect kinin analogues of the sequence Phe-Phe-ψ[CN4]-Ala-Trp-Gly-NH2 containing (L-Phe2,L-Ala3) and (L-Phe2,D-Ala3) stereochemical variants of the tetrazole moiety, a mimic of the type VI β-turn, demonstrate significant agonist and partial antagonist activity, respectively, in a cricket diuretic bioassay. A comparison of the solution conformations of these two stereochemical variants indicates a structural basis for their divergent bioactivities. The (D-Phe2,D-Ala3) stereochemical variant was synthesized and found to demonstrate significant agonist activity. The results further define stereochemical requirements for the diuretic activity of insect kinins in crickets and provide valuable information for the design of biostable analogues capable of disrupting digestive and diuretic processes in pest insects.

5

Chelating ability of proctolin tetrazole analogue

76%

Łodyga-Chruścińska E., Sanna D., Micera G., Chruściński L., Olejnik J., Nachman R. J., Zabrocki J.

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2006

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vol. 53

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issue 1

65-72

EN

The aim of the investigation was to establish the chelating ability of a new proctolin analogue of the sequence Arg-Tyr-LeuΨ[CN4]Ala-Thr towards copper(II) ions. The insertion of the tetrazole moiety into the peptide sequence has considerably changed the coordination ability of the ligand. Potentiometric and spectroscopic (UV-Vis, CD, EPR) results indicate that the incorporation of 1,5-disubstituted tetrazole ring favours the formation of a stable complex form of CuH-1L. This 4N coordination type complex is the dominant species in the physiological pH range. The tetrazole moiety provides one of these nitrogens. The data indicate that Cu(II) ions are strongly trapped inside the peptide backbone. These findings suggest that Cu(II) can hold peptide chains in a bent conformation. This bent conformation may be essential for bioactivity of the tetrazole peptides.

6

Effect of tetrazole moiety on coordinating efficiency of deltorphin.

76%

Łodyga-Chruścińska E., Ołdziej S., Micera G., Sanna D., Chruściński L., Olczak J., Zabrocki J.

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vol. 51

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issue 1

93-106

EN

A study of the effect of the tetrazole moiety, a cis-amide bond surrogate, on the Cu(II) coordinating properties of oligopeptides is reported. Insertion of the tetrazole moiety Ψ[CN4] into the peptide sequence of [D-Ala2]deltorphin I changes considerably the coordination ability of the peptide. Potentiometric and spectroscopic results show that if the tetrazole moiety is in a suitable position in the peptide chain, i.e. it follows the second residue, a stable CuL species involving 3N coordination is formed in the physiological pH range. The tetrazole Ψ[CN4] ring provides one of these nitrogens. The data indicate that Cu(II) ions are strongly trapped inside a bent peptide backbone. The peptide conformation changes achieved by Cu(II) coordination may be essential for the binding of tetrazole deltorphins at opiate receptors.

7

Search for new synthetic immunosuppressants II. Tetrazole analogues of hymenistatin I.

76%

Zubrzak P., Kociołek K., Smoluch M., Silberring J., Kowalski M. L., Szkudlińska B., Zabrocki J.

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2001

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vol. 48

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issue 4

1151-1154

EN

Linear and cyclic hymenistatin I (HS I) analogues with dipeptide segments Ile2-Pro3, Pro3-Pro4 and Val6-Pro7 replaced by their tetrazole analogues Ile-Ψ[CN4]-Ala3, Pro3-Ψ[CN4]-Ala4 and Val6-Ψ[CN4]-Alawere synthesized by the solid phase peptide synthesis method and cyclized with the TBTU and/or HATU reagent. The peptides were examined for their immunosuppressive activity in the lymphocyte proliferation test (LPT).

8

New bradykinin B2 receptor antagonists - influence of C-terminal segment modifications on their pharmacological properties

64%

Śleszyńska M., Kwiatkowska A., Sobolewski D., Wierzba T., Katarzyńska J., Zabrocki J., Borovickova L., Slaninová J., Prahl A.

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EN

In the present study we describe the synthesis and some pharmacological properties of eight new analogues of bradykinin (BK). Two peptides were designed by substitution of position 7 or 8 of the known [d-Arg0,Hyp3,Thi5,8,d-Phe7]BK antagonist (Stewart's antagonist) with l-pipecolic acid (l-Pip). The next two analogues were obtained by replacement of the d-Phe residue in position 7 of the Stewart's peptide with l-β2-isoproline (l-β2-iPro) or l-β3-homoproline (l-β3-hPro). The four analogues mentioned above were also prepared in N-acylated form with 1-adamantaneacetic acid (Aaa). Biological activity of the compounds was assessed by isolated rat uterus and rat blood pressure tests. Our results showed that l-Pip in position 7 slightly increased antagonistic potency in the blood pressure test, but it turned the analogue into an agonist in the rat uterus test. Replacement of Thi by l-Pip in position 8 also enhanced antagonism in the rat pressure test but preserved the antagonism in the rat uterus test. l-β2-iPro or l-β3-hPro in position 7 decreased the potencies in both tests. We also demonstrated that acylation of the N-terminus did not increase, as was claimed previously, the antagonistic potencies of the resulting peptides. The results thus support the hypothesis about the existence of different types of BK receptors in the rat uterus and blood vessels. Our studies provide new information about the structure-activity relationship of BK antagonists which may help in designing more potent BK receptor blockers.

Refine search results

New analogue of cyclolinopeptide B modified by amphiphilic residue of α-hydroxymethylmethionine.

DALDA analogues containing α-hydroxymethylamino acids.

A novel cis-peptide bond motif inducing β-turn type VI. The synthesis of enkephalin analogues modified with 4-aminopyroglutamic acid.

Stereochemistry of insect kinin tetrazole analogues and their diuretic activity in crickets.

Chelating ability of proctolin tetrazole analogue

Effect of tetrazole moiety on coordinating efficiency of deltorphin.

Search for new synthetic immunosuppressants II. Tetrazole analogues of hymenistatin I.

New bradykinin B2 receptor antagonists - influence of C-terminal segment modifications on their pharmacological properties