Jan Lukszo - Academia.edu (original) (raw)
Papers by Jan Lukszo
Chemischer Informationsdienst, Mar 13, 1979
ChemInform Abstract Der Phosphinsäureester (II) lagert sich in der Hitze an Aldimine (I) an. Die ... more ChemInform Abstract Der Phosphinsäureester (II) lagert sich in der Hitze an Aldimine (I) an. Die Addukte (III) liefern nach Hydrolyse in Ameisensäure die Aminophosphonsäuren (IV). Aminophosphonsäuren (VIII) ohne Substituenten am Stickstoff erhält man, wenn man die Sehiffschen Basen des Phenylcyclopentylamins (VI) einsetzt. (IR-und NMR-Daten).
Chemischer Informationsdienst, Aug 28, 1979
ChemInform Abstract Das Tosylat (I) wird zum Bromid (II) umgesetzt. Reaktion von (II) mit Benzyli... more ChemInform Abstract Das Tosylat (I) wird zum Bromid (II) umgesetzt. Reaktion von (II) mit Benzylisocyanid in Gegenwart von LiNiPrz liefert das Cyclopentancyanid (III), das roh zur Titelverbindung (IV) hydrolysiert wird.
Chemischer Informationsdienst, Aug 22, 1978
Scientific Reports, Mar 19, 2018
Tick saliva is a rich source of modulators of vascular biology. We have characterized Ixonnexin, ... more Tick saliva is a rich source of modulators of vascular biology. We have characterized Ixonnexin, a member of the "Basic-tail" family of salivary proteins from the tick Ixodes scapularis. Ixonnexin is a 104 residues (11.8 KDa), non-enzymatic basic protein which contains 3 disulfide bonds and a C-terminal rich in lysine. It is homologous to SALP14, a tick salivary FXa anticoagulant. Ixonnexin was produced by ligation of synthesized fragments (51-104) and (1-50) followed by folding. Ixonnexin, like SALP14, interacts with FXa. Notably, Ixonnexin also modulates fibrinolysis in vitro by a unique salivary mechanism. Accordingly, it accelerates plasminogen activation by tissue-type plasminogen activator (t-PA) with Km 100 nM; however, it does not affect urokinase-mediated fibrinolysis. Additionally, lysine analogue ε-aminocaproic acid inhibits Ixonnexin-mediated plasmin generation implying that lysinebinding sites of Kringle domain(s) of plasminogen or t-PA are involved in this process. Moreover, surface plasmon resonance experiments shows that Ixonnexin binds t-PA, and plasminogen (K D 10 nM), but not urokinase. These results imply that Ixonnexin promotes fibrinolysis by supporting the interaction of plasminogen with t-PA through formation of an enzymatically productive ternary complex. Finally, in vivo experiments demonstrates that Ixonnexin inhibits FeCl 3-induced thrombosis in mice. Ixonnexin emerges as novel modulator of fibrinolysis which may also affect parasite-vector-host interactions.
Chemischer Informationsdienst, Aug 2, 1977
Chemischer Informationsdienst, 1978
Die aus den entsprechenden aromatischen Aldehyden und 1‐Phenylcyclopentylamin erhaltenen Schiffsc... more Die aus den entsprechenden aromatischen Aldehyden und 1‐Phenylcyclopentylamin erhaltenen Schiffschen Basen (I) setzen sich leicht mit Diethylphosphit zu den N‐substituierten α‐Aminobenzylphosphonaten (II) um.
Journal of High Resolution Chromatography, 1994
Zeitschrift für Naturforschung B, 1986
Bovine Serum Albumin (BSA) was spin labeled using the active esters 3 and 5 containing a nitroxyl... more Bovine Serum Albumin (BSA) was spin labeled using the active esters 3 and 5 containing a nitroxyl radical to give the spin labeled BSA derivatives 4 and 6. Spin labeled C D TA , DTPA and TTHA chelating agents 10, 13 and 16 and the corresponding BSA derivatives 17, 18 and 19 and their gadolinium complexes 20, 21 and 22 were synthesized. All these BSA derivatives were evaluated as possible contrast enhancing agents for NMR imaging by measurement of spin-lattice (T1) and spin-spin (T2) relaxations and by calculations of relaxivities i.e., slopes of 1/T1 versus concentration plots. The spin labeled BSA-complexon-gadolinium conjugates 20, 21 and 22 were found to have better relaxation times and relaxivities than the BSA spin labeled derivatives 4, 6, 17, 18 and 19. The spin count for the BSA derivatives 4, 6, 17, 18 and 19 and for their gadolinium conjugates 20, 21 and 22 was found to be between 9 -1 0 spins/molecule of the protein. The gadolinium conjugates 20, 21 and 22 of spin labeled...
PloS one, 2015
A group of peptides from the salivary gland of the tick Hyalomma marginatum rufipes, a vector of ... more A group of peptides from the salivary gland of the tick Hyalomma marginatum rufipes, a vector of Crimean Congo hemorrhagic fever show weak similarity to the madanins, a group of thrombin-inhibitory peptides from a second tick species, Haemaphysalis longicornis. We have evaluated the anti-serine protease activity of one of these H. marginatum peptides that has been given the name hyalomin-1. Hyalomin-1 was found to be a selective inhibitor of thrombin, blocking coagulation of plasma and inhibiting S2238 hydrolysis in a competitive manner with an inhibition constant (Ki) of 12 nM at an ionic strength of 150 mM. It also blocks the thrombin-mediated activation of coagulation factor XI, thrombin-mediated platelet aggregation, and the activation of coagulation factor V by thrombin. Hyalomin-1 is cleaved at a canonical thrombin cleavage site but the cleaved products do not inhibit coagulation. However, the C-terminal cleavage product showed non-competitive inhibition of S2238 hydrolysis. A...
Letters in Peptide Science, 1996
Several side reactions have been detected for cysteine-containing peptides. During the synthesis ... more Several side reactions have been detected for cysteine-containing peptides. During the synthesis of C-terminal cysteine peptides, a base-catalyzed elimination of the sulfhydryl-protected side-chain to afford the dehydroalanine derivative followed by a nucleophilic addition to the alkene was observed. MALDI-TOF analysis was a useful analytical technique to determine this phenomenon.
Zeitschrift für Naturforschung B, 1986
Spermidine, spermine and other polyamines 1-5 were selectively protected at the terminal primary ... more Spermidine, spermine and other polyamines 1-5 were selectively protected at the terminal primary amino functions without affecting the secondary amino groups using N-ethoxycarbonyl-phthalimide (15), the Nefkens’ reagent. Three representative products, 17, 18 and 20, readily underwent acylation at the secondary amino nitrogen to give the corresponding compounds 21-26. Selective deprotection of two representative samples 22 and 25 at the primary amino function by hydrazinolysis yielded the corresponding derivatives 27 and 28 with free primary amino groups. In summary, the application of Nefkens’ reagent for the terminal protection of primary amino groups in various polyamines results in a simple, efficient and selective one-step procedure using commercially available reagents.
Zeitschrift für Naturforschung B, 1996
The synthesis and a few properties of hexadecyl 2-[N,N-dimethyl-N-(2,2,6.6-tetramethyll- oxyl-pip... more The synthesis and a few properties of hexadecyl 2-[N,N-dimethyl-N-(2,2,6.6-tetramethyll- oxyl-piperidin-4-yl)ammonio] ethyl phosphate are described. This compound is a spin labeled analog of the antineoplastic drug hexadecylphosphocholine (Miltefosine)
Zeitschrift für Naturforschung B, 1985
Four novel spin labeled azacrown ethers containing either endo- or exo-cyclic nitroxyl moieties ... more Four novel spin labeled azacrown ethers containing either endo- or exo-cyclic nitroxyl moieties were synthesized by short and convenient routes. These compounds should be of interest in biological studies of membranes using ESR spectroscopy.
Molecular Mechanisms of Metal Toxicity and Carcinogenesis, 2001
Zeitschrift für Naturforschung B, 1994
Several synthetic approaches are explored for the preparation of polyamines which are cross-linke... more Several synthetic approaches are explored for the preparation of polyamines which are cross-linked at the central, secondary nitrogen moiety. Diethylenetriamine, norspermidine and spermidine were used as examples.
Drugs of the Future, 1985
Zeitschrift für Naturforschung B, 1987
Sodium complexes 3 and 5 of the spin labeled monoazacrown ethers 2,2,15,15-tetramethyl-1-aza- 4,7... more Sodium complexes 3 and 5 of the spin labeled monoazacrown ethers 2,2,15,15-tetramethyl-1-aza- 4,7,10,13-tetraoxacyclopentadecane-1-oxyl (2) and 1,4,7,10-tetraoxa-13-(2′,2′,6′,6′-tetramethyl-piperidine-1′-oxyl-4′-yl)azacyclopentadecane (4) were synthesized and studied by EPR and ENDOR spectroscopies. The hyperfine splitting parameter and the g value of the complex 5, containing the exocyclic nitroxyl moiety, were identical to the parent complexon 4, i.e., aN = 15.6 G. g = 2.0060 ± 0.0001. In contrast, the data for the complex 3, containing the endocyclic nitroxyl moiety were different. Thus, the spectrum of the complex 3 was a triplet of quartets with aN = 15.7 G. aNa = 2.47 G, g = 2.0062 ± 0.0001, whereas the spectrum of the parent complexon 2 was a triplet with aN = 15.5 G, g = 2.0059 ± 0.0001. The interaction between the sodium cation and the nitroxyl moiety in 3 was further confirmed by the sodium ENDOR transition at 7.27 MHz
Tetrahedron, 1985
Influence of structure on the reduction of nltroxyl spin labels by ascorbic acid wss examined usi... more Influence of structure on the reduction of nltroxyl spin labels by ascorbic acid wss examined using both plperidlne and pyrrolidine nitroxyls. A fivefold molar excess of sscotblc acid and pH of 7.4 were used. The nirroxyl concentrstlon was meaeured by electron spin resonance spectroaetry. The five-membered (pyrrolldlne) nltroxyls were more 6tsble than the six-membered derivatives. Ring substltuents also influenced the reaction. The anionic derivatives were amore stable than the unlonlxed compounds which, in turn, were more stable than the amine8 (cation6 at pW 7.4). Because of the presence of an unpaired electron, nitroxyl spin labels can be used to enhance contrast in proton a6gnetLc resonsnce imaging (WI) and thereby increase rhe diagnostic usefulnese of this new technique (I). Potential applications of contrast-enhancing nltroxyls include: differentiation of isomagnetic tissues, direct evaluation of organ function and pathology, and evaluation of tissue perfusion (Z-4). Two water soluble nltroxyls, succlnic acid N-(2,2,6,6-tetramethyl-I-oxyl-4-piperidinyl) monoamide [6C] and 3-carboxy-2,2,5,5-tetramethylpyrrol%dine-I-oxyl [5B] have been administered lntrsvenously to experimental animals prior to proton imaging by magnetic resonance techniques. These nltroxyls sided in the definition of renal functional abnormalities, defects in the bloodbrain-barrier, and perfusion abnormalities in infarcted myocardlum. Both nitroxyls were extensively reduced in viva, presumably to their corresponding hydroxylamine derivatives (5). This reduction process is undesirable, because the hydroxylamine is not parsmagnetic and produces no contrast enhancing effect in NRI. Nltroxyl derivatives with high resistance to in vlvo reduction-would, therefore, be advantageous for contrast enhancement. The rates of reduction of 6C and 51 by aecorbic actd have been shown to differ significantly when measured under identical conditions (S), indicating that chemical structure influences the rate of biologic reduction and that certain structures may be particularly resistant to reduction
Journal of Pharmaceutical Sciences, 1994
A series of TEPA, Thio-TEPA, Seleno-TEPA, and azetidine analogs, including congeners containing a... more A series of TEPA, Thio-TEPA, Seleno-TEPA, and azetidine analogs, including congeners containing an aminoxyl moiety, were synthesized and evaluated in vivo for anticancer activity against the murine lymphocytic leukemia P388. All aziridine derivatives were found to be active with an increase in life span ranging from 42% to 272%, and all azetidine analogs were rated as inactive with one marginal exception. An attempt was made to rationalize the results on the basis of the lipophilic properties of the compounds. The most active compound (8) possessed the most balanced lipophilic properties, corresponding to a log P value near zero.
Chemischer Informationsdienst, Mar 13, 1979
ChemInform Abstract Der Phosphinsäureester (II) lagert sich in der Hitze an Aldimine (I) an. Die ... more ChemInform Abstract Der Phosphinsäureester (II) lagert sich in der Hitze an Aldimine (I) an. Die Addukte (III) liefern nach Hydrolyse in Ameisensäure die Aminophosphonsäuren (IV). Aminophosphonsäuren (VIII) ohne Substituenten am Stickstoff erhält man, wenn man die Sehiffschen Basen des Phenylcyclopentylamins (VI) einsetzt. (IR-und NMR-Daten).
Chemischer Informationsdienst, Aug 28, 1979
ChemInform Abstract Das Tosylat (I) wird zum Bromid (II) umgesetzt. Reaktion von (II) mit Benzyli... more ChemInform Abstract Das Tosylat (I) wird zum Bromid (II) umgesetzt. Reaktion von (II) mit Benzylisocyanid in Gegenwart von LiNiPrz liefert das Cyclopentancyanid (III), das roh zur Titelverbindung (IV) hydrolysiert wird.
Chemischer Informationsdienst, Aug 22, 1978
Scientific Reports, Mar 19, 2018
Tick saliva is a rich source of modulators of vascular biology. We have characterized Ixonnexin, ... more Tick saliva is a rich source of modulators of vascular biology. We have characterized Ixonnexin, a member of the "Basic-tail" family of salivary proteins from the tick Ixodes scapularis. Ixonnexin is a 104 residues (11.8 KDa), non-enzymatic basic protein which contains 3 disulfide bonds and a C-terminal rich in lysine. It is homologous to SALP14, a tick salivary FXa anticoagulant. Ixonnexin was produced by ligation of synthesized fragments (51-104) and (1-50) followed by folding. Ixonnexin, like SALP14, interacts with FXa. Notably, Ixonnexin also modulates fibrinolysis in vitro by a unique salivary mechanism. Accordingly, it accelerates plasminogen activation by tissue-type plasminogen activator (t-PA) with Km 100 nM; however, it does not affect urokinase-mediated fibrinolysis. Additionally, lysine analogue ε-aminocaproic acid inhibits Ixonnexin-mediated plasmin generation implying that lysinebinding sites of Kringle domain(s) of plasminogen or t-PA are involved in this process. Moreover, surface plasmon resonance experiments shows that Ixonnexin binds t-PA, and plasminogen (K D 10 nM), but not urokinase. These results imply that Ixonnexin promotes fibrinolysis by supporting the interaction of plasminogen with t-PA through formation of an enzymatically productive ternary complex. Finally, in vivo experiments demonstrates that Ixonnexin inhibits FeCl 3-induced thrombosis in mice. Ixonnexin emerges as novel modulator of fibrinolysis which may also affect parasite-vector-host interactions.
Chemischer Informationsdienst, Aug 2, 1977
Chemischer Informationsdienst, 1978
Die aus den entsprechenden aromatischen Aldehyden und 1‐Phenylcyclopentylamin erhaltenen Schiffsc... more Die aus den entsprechenden aromatischen Aldehyden und 1‐Phenylcyclopentylamin erhaltenen Schiffschen Basen (I) setzen sich leicht mit Diethylphosphit zu den N‐substituierten α‐Aminobenzylphosphonaten (II) um.
Journal of High Resolution Chromatography, 1994
Zeitschrift für Naturforschung B, 1986
Bovine Serum Albumin (BSA) was spin labeled using the active esters 3 and 5 containing a nitroxyl... more Bovine Serum Albumin (BSA) was spin labeled using the active esters 3 and 5 containing a nitroxyl radical to give the spin labeled BSA derivatives 4 and 6. Spin labeled C D TA , DTPA and TTHA chelating agents 10, 13 and 16 and the corresponding BSA derivatives 17, 18 and 19 and their gadolinium complexes 20, 21 and 22 were synthesized. All these BSA derivatives were evaluated as possible contrast enhancing agents for NMR imaging by measurement of spin-lattice (T1) and spin-spin (T2) relaxations and by calculations of relaxivities i.e., slopes of 1/T1 versus concentration plots. The spin labeled BSA-complexon-gadolinium conjugates 20, 21 and 22 were found to have better relaxation times and relaxivities than the BSA spin labeled derivatives 4, 6, 17, 18 and 19. The spin count for the BSA derivatives 4, 6, 17, 18 and 19 and for their gadolinium conjugates 20, 21 and 22 was found to be between 9 -1 0 spins/molecule of the protein. The gadolinium conjugates 20, 21 and 22 of spin labeled...
PloS one, 2015
A group of peptides from the salivary gland of the tick Hyalomma marginatum rufipes, a vector of ... more A group of peptides from the salivary gland of the tick Hyalomma marginatum rufipes, a vector of Crimean Congo hemorrhagic fever show weak similarity to the madanins, a group of thrombin-inhibitory peptides from a second tick species, Haemaphysalis longicornis. We have evaluated the anti-serine protease activity of one of these H. marginatum peptides that has been given the name hyalomin-1. Hyalomin-1 was found to be a selective inhibitor of thrombin, blocking coagulation of plasma and inhibiting S2238 hydrolysis in a competitive manner with an inhibition constant (Ki) of 12 nM at an ionic strength of 150 mM. It also blocks the thrombin-mediated activation of coagulation factor XI, thrombin-mediated platelet aggregation, and the activation of coagulation factor V by thrombin. Hyalomin-1 is cleaved at a canonical thrombin cleavage site but the cleaved products do not inhibit coagulation. However, the C-terminal cleavage product showed non-competitive inhibition of S2238 hydrolysis. A...
Letters in Peptide Science, 1996
Several side reactions have been detected for cysteine-containing peptides. During the synthesis ... more Several side reactions have been detected for cysteine-containing peptides. During the synthesis of C-terminal cysteine peptides, a base-catalyzed elimination of the sulfhydryl-protected side-chain to afford the dehydroalanine derivative followed by a nucleophilic addition to the alkene was observed. MALDI-TOF analysis was a useful analytical technique to determine this phenomenon.
Zeitschrift für Naturforschung B, 1986
Spermidine, spermine and other polyamines 1-5 were selectively protected at the terminal primary ... more Spermidine, spermine and other polyamines 1-5 were selectively protected at the terminal primary amino functions without affecting the secondary amino groups using N-ethoxycarbonyl-phthalimide (15), the Nefkens’ reagent. Three representative products, 17, 18 and 20, readily underwent acylation at the secondary amino nitrogen to give the corresponding compounds 21-26. Selective deprotection of two representative samples 22 and 25 at the primary amino function by hydrazinolysis yielded the corresponding derivatives 27 and 28 with free primary amino groups. In summary, the application of Nefkens’ reagent for the terminal protection of primary amino groups in various polyamines results in a simple, efficient and selective one-step procedure using commercially available reagents.
Zeitschrift für Naturforschung B, 1996
The synthesis and a few properties of hexadecyl 2-[N,N-dimethyl-N-(2,2,6.6-tetramethyll- oxyl-pip... more The synthesis and a few properties of hexadecyl 2-[N,N-dimethyl-N-(2,2,6.6-tetramethyll- oxyl-piperidin-4-yl)ammonio] ethyl phosphate are described. This compound is a spin labeled analog of the antineoplastic drug hexadecylphosphocholine (Miltefosine)
Zeitschrift für Naturforschung B, 1985
Four novel spin labeled azacrown ethers containing either endo- or exo-cyclic nitroxyl moieties ... more Four novel spin labeled azacrown ethers containing either endo- or exo-cyclic nitroxyl moieties were synthesized by short and convenient routes. These compounds should be of interest in biological studies of membranes using ESR spectroscopy.
Molecular Mechanisms of Metal Toxicity and Carcinogenesis, 2001
Zeitschrift für Naturforschung B, 1994
Several synthetic approaches are explored for the preparation of polyamines which are cross-linke... more Several synthetic approaches are explored for the preparation of polyamines which are cross-linked at the central, secondary nitrogen moiety. Diethylenetriamine, norspermidine and spermidine were used as examples.
Drugs of the Future, 1985
Zeitschrift für Naturforschung B, 1987
Sodium complexes 3 and 5 of the spin labeled monoazacrown ethers 2,2,15,15-tetramethyl-1-aza- 4,7... more Sodium complexes 3 and 5 of the spin labeled monoazacrown ethers 2,2,15,15-tetramethyl-1-aza- 4,7,10,13-tetraoxacyclopentadecane-1-oxyl (2) and 1,4,7,10-tetraoxa-13-(2′,2′,6′,6′-tetramethyl-piperidine-1′-oxyl-4′-yl)azacyclopentadecane (4) were synthesized and studied by EPR and ENDOR spectroscopies. The hyperfine splitting parameter and the g value of the complex 5, containing the exocyclic nitroxyl moiety, were identical to the parent complexon 4, i.e., aN = 15.6 G. g = 2.0060 ± 0.0001. In contrast, the data for the complex 3, containing the endocyclic nitroxyl moiety were different. Thus, the spectrum of the complex 3 was a triplet of quartets with aN = 15.7 G. aNa = 2.47 G, g = 2.0062 ± 0.0001, whereas the spectrum of the parent complexon 2 was a triplet with aN = 15.5 G, g = 2.0059 ± 0.0001. The interaction between the sodium cation and the nitroxyl moiety in 3 was further confirmed by the sodium ENDOR transition at 7.27 MHz
Tetrahedron, 1985
Influence of structure on the reduction of nltroxyl spin labels by ascorbic acid wss examined usi... more Influence of structure on the reduction of nltroxyl spin labels by ascorbic acid wss examined using both plperidlne and pyrrolidine nitroxyls. A fivefold molar excess of sscotblc acid and pH of 7.4 were used. The nirroxyl concentrstlon was meaeured by electron spin resonance spectroaetry. The five-membered (pyrrolldlne) nltroxyls were more 6tsble than the six-membered derivatives. Ring substltuents also influenced the reaction. The anionic derivatives were amore stable than the unlonlxed compounds which, in turn, were more stable than the amine8 (cation6 at pW 7.4). Because of the presence of an unpaired electron, nitroxyl spin labels can be used to enhance contrast in proton a6gnetLc resonsnce imaging (WI) and thereby increase rhe diagnostic usefulnese of this new technique (I). Potential applications of contrast-enhancing nltroxyls include: differentiation of isomagnetic tissues, direct evaluation of organ function and pathology, and evaluation of tissue perfusion (Z-4). Two water soluble nltroxyls, succlnic acid N-(2,2,6,6-tetramethyl-I-oxyl-4-piperidinyl) monoamide [6C] and 3-carboxy-2,2,5,5-tetramethylpyrrol%dine-I-oxyl [5B] have been administered lntrsvenously to experimental animals prior to proton imaging by magnetic resonance techniques. These nltroxyls sided in the definition of renal functional abnormalities, defects in the bloodbrain-barrier, and perfusion abnormalities in infarcted myocardlum. Both nitroxyls were extensively reduced in viva, presumably to their corresponding hydroxylamine derivatives (5). This reduction process is undesirable, because the hydroxylamine is not parsmagnetic and produces no contrast enhancing effect in NRI. Nltroxyl derivatives with high resistance to in vlvo reduction-would, therefore, be advantageous for contrast enhancement. The rates of reduction of 6C and 51 by aecorbic actd have been shown to differ significantly when measured under identical conditions (S), indicating that chemical structure influences the rate of biologic reduction and that certain structures may be particularly resistant to reduction
Journal of Pharmaceutical Sciences, 1994
A series of TEPA, Thio-TEPA, Seleno-TEPA, and azetidine analogs, including congeners containing a... more A series of TEPA, Thio-TEPA, Seleno-TEPA, and azetidine analogs, including congeners containing an aminoxyl moiety, were synthesized and evaluated in vivo for anticancer activity against the murine lymphocytic leukemia P388. All aziridine derivatives were found to be active with an increase in life span ranging from 42% to 272%, and all azetidine analogs were rated as inactive with one marginal exception. An attempt was made to rationalize the results on the basis of the lipophilic properties of the compounds. The most active compound (8) possessed the most balanced lipophilic properties, corresponding to a log P value near zero.