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Structural studies of cysteine proteases and their inhibitors.

100%

Grzonka Z., Jankowska E., Kasprzykowski F., Kasprzykowska R., Łankiewicz L., Wiczk W., Wieczerzak E., Ciarkowski J., Drabik P., Janowski R., Kozak M., Jaskólski M., Grubb A.

2001

vol. 48

issue 1

1-20

Cysteine proteases (CPs) are responsible for many biochemical processes occurring in living organisms and they have been implicated in the development and progression of several diseases that involve abnormal protein turnover. The activity of CPs is regulated among others by their specific inhibitors: cystatins. The main aim of this review is to discuss the structure-activity relationships of cysteine proteases and cystatins, as well as of some synthetic inhibitors of cysteine proteases structurally based on the binding fragments of cystatins.

Interactions of antitumor triazoloacridinones with DNA

75%

Koba M., Konopa J.

2007

vol. 54

issue 2

297-306

Triazoloacridinones (TA) are a new group of potent antitumor compounds, from which the most active derivative, C-1305, has been selected for extended preclinical trials. This study investigated the mechanism of TA binding to DNA. Initially, for selected six TA derivatives differing in chemical structures as well as cytotoxicity and antitumor activity, the capability of noncovalent DNA binding was analyzed. We showed that all triazoloacridinones studied stabilized the DNA duplex at a low-concentration buffer but not at a salt concentration corresponding to that in cells. DNA viscometric studies suggested that intercalation to DNA did not play a major role in the mechanism of the cytotoxic action of TA. Studies involving cultured cells revealed that triazoloacridinone C-1305 after previous metabolic activation induced the formation of interstrand crosslinks in DNA of some tumor and fibroblast cells in a dose dependent manner. However, the detection of crosslink formation was possible only when the activity of topoisomerase II in cells was lowered. Furthermore, it was impossible to validate the relevance of the ability to crosslink DNA to biological activity of TA derivatives.

Cyclic enkephalin-deltorphin hybrids containing a carbonyl bridge: structure and opioid activity

75%

Ciszewska M., Ruszczyńska K., Oleszczuk M., Chung N., Witkowska E., Schiller P., Wójcik J., Izdebski J.

2011

vol. 58

issue 2

225-230

Six hybrid N-ureidoethylamides of octapeptides in which an N-terminal cyclic structure related to enkephalin was elongated by a C-terminal fragment of deltorphin were synthesized on MBHA resin. The synthetic procedure involved deprotection of Boc groups with HCl/dioxane and cleavage of the peptide resin with 45 % TFA in DCM. d-Lys and d-Orn were incorporated in position 2, and Lys, Orn, Dab, or Dap in position 5. The side chains of the dibasic amino function were protected with the Fmoc group. This protection was removed by treatment with 55 % piperidine in DMF, and cyclization was achieved by treatment with bis-(4-nitrophenyl)carbonate. Using various combinations of dibasic amino acids, peptides containing a 17-, 18-, 19- or 20-membered ring structure were obtained. The peptides were tested in the guinea-pig ileum (GPI) and mouse vas deferens (MVD) assays. Diverse opioid activities were observed, depending on the size of the ring. Extension of the enkephalin sequence at the C-terminus by a deltorphin fragment resulted in a change of receptor selectivity in favor of the δ receptor. The conformational propensities of selected peptides were determined using the EDMC method in conjunction with data derived from NMR experiments carried out in water. This approach allowed proper examination of the dynamical behavior of these small peptides. The results were compared with those obtained earlier with corresponding N-(ureidoethyl)pentapeptide amides.

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3 Acta Biochimica Polonica

1 2011

1 2007

1 2001

1 Chung N.

1 Ciarkowski J.

1 Ciszewska M.

1 Drabik P.

1 Grubb A.

1 Grzonka Z.

1 Izdebski J.

1 Jankowska E.

1 Janowski R.

1 Jaskólski M.

1 Kasprzykowska R.

1 Kasprzykowski F.

1 Koba M.

1 Konopa J.

1 Kozak M.

1 Oleszczuk M.

1 Ruszczyńska K.

1 Schiller P.

1 Wiczk W.

1 Wieczerzak E.

1 Witkowska E.

1 Wójcik J.

1 Łankiewicz L.

Search results

Structural studies of cysteine proteases and their inhibitors.

Interactions of antitumor triazoloacridinones with DNA

Cyclic enkephalin-deltorphin hybrids containing a carbonyl bridge: structure and opioid activity