Effect of protective atmosphere on color of goose meat.

The objective of the work was to characterize the color of the of the goose breast meat packaged in protective atmosphere and stored in the refrigerated conditions. The aim was realized by determination of total heme pigment concentration; relative concentration of myoglobin, oxymyoglobin, and metmyoglobin; parameters of color L* (lightness), a* (redness), and b* (yellowness); and sensory evaluation of the surface color. The experimental material was White Koluda goose boneless breast meat with the skin from industrial slaughter. The following 2 protective atmospheres were used in the study: vacuum and modified atmosphere (MA) consisting of 80% O2 and 20% CO2. The muscles packed in protective atmosphere were examined on d 4, 7, 11, and 14 of storage. A control sample was goose breast meat stored in air and tested after 24 h after slaughter. The total pigment concentration decreased gradually within 14 d of storage for samples packed in 2 types of atmospheres. The increase in relative concentration of metmyoglobin and the decrease in oxymyoglobin relative concentration in total heme pigments in the meat stored in MA was noticed. However, in all times of storage, the relative concentration of the 3 samples of myoglobin forms stored in vacuum was unchanged. The color parameters (L*, a*, b*) did not change for 14 d of storage in the muscles packed in vacuum. One can state a decrease of the value of the color parameter a* as well as an increase of the value of the color parameter b* in the samples packed in MA. From d 11 to 14 of storage, goose meat packed under MA had lower sensory evaluation intensity of color than muscles under vacuum. The obtained data indicated that the surface color of goose breast meat packed in MA (consisting of 80% O2, 20% CO2) or vacuum packed was maintained for 11 and 14 d, respectively.

Chemical composition and amino acid profiles of goose muscles from native Polish breeds.

The aim of the study was to compare the chemical and amino acid composition of breast (pectoralis major) and thigh (biceps femoris) muscles in 17-wk-old geese from 2 Polish conservative flocks: Rypinska (Ry, n = 20) and Garbonosa (Ga, n = 20). The geese were fed ad libitum during the experimental period on the same complete feed. Genotypes affected the moisture and fat content of breast and thigh meat. The Ga geese were characterized by higher moisture as well as lower fat lipid content compared with the Ry breast and thigh muscles. The amino acid proportions of meat proteins depended on the goose flock and type of muscles, where significant differences were found. The proteins of Ga breast muscles contained more glutamic acid, glycine, lysine, tryptophan, histidine, and methionine, and less aspartic acid, proline, serine, leucine, valine, phenyloalanine, tyrosine, and threonine than the Ry geese (P ≤ 0.05). The proteins of Ry thigh muscles were characterized by higher content of proline, serine, and essential amino acids (without lysine and methionine) and lower glutamic and asparagine acid, alanine, and glycine compared with the Ga flock. According to the Food and Agriculture Organization of the United Nations/World Health Organization (1991) standard, tryptophan was the amino acid limiting the nutritional value of meat proteins of Ry breast muscles (amino acid score for tryptophan = 90%). Except for tryptophan, the meat proteins of the investigated raw materials contained more essential amino acids than the standard. The total content of essential amino acids for all investigated muscles was also higher (52.51 to 55.54%) than the standard (33.90%). It is evident that muscle protein from both flocks of geese have been characterized by high nutritional value. The values of the essential amino acid index of breast muscle proteins were similar in both flocks.

Impact of frozen storage on some functional properties and sensory evaluation of goose meat.

The objective of this study was to investigate the changes in the functional properties (pH, water holding capacity [WHC], water binding capacity [WBC], cooking losses [CL], defrosting losses [DL]), color parameters (L*, a*, b*, C, h°, ΔE), and sensory evaluation of breast (BM) and leg (LM) muscles from 17-wk-old female White Koluda geese packaged in a vacuum and stored in frozen conditions at -20°C. During 17 wk, the geese were fed ad libitum on the same complete feed. The samples (18 BM and 18 LM) from the right part of the carcasses were stored for 30, 90, 80, 270, and 365 d. The changes in functional properties were established using a standard method used in the meat industry, according to Wierbicki et al. (1962), Grau and Hamm (1953), and CIE, (1986). Sensory evaluation was established according to defined parameters in PN-ISO 8586-2:2008. The time of frozen storage affected the decrease in WHC and WBC of BM and LM. Moreover, the LM can be characterized by a higher WHC and WBC compared to the values in the BM. It was established that CL and DL, which are the critical quality indicators, negatively increased in BM and LM during frozen storage. Considering the sensory evaluation and L*, a*, b*, C, it was established that changes in BM and LM during frozen storage were unfavorable. The scores given for smell, taste, consistency, and general appearance, as also L*, a*, and b* parameters decreased significantly during frozen storage. In addition, BM received lower scores for general appearance (at 180th and 270th day), and L* (in all frozen storage), than LM. BM and LM characterized the parameter ΔE in the range of 0.44 to 1.45, which allowed us to conclude that slight color differences were visible in these muscles (<2). Based on the study, it can be suggested that the optimal frozen storage time for BM and LM should not be longer than 180 d.

The effects of sous-vide, microwave cooking and stewing of goose meat on fatty acid profile and lipid indices.

The effect of sous-vide (S-V), microwave cooking (M) and stewing (S) on the fatty acid profile and lipid indices of goose meat was investigated. The research material involved breast muscles (24 with skin and 24 without skin) cut from carcasses of 17-week-old females "Polish oat geese." Gas chromatography was used to establish the fatty acid profile and lipid indices were calculated. The kind of heat treatment and the type of goose meat (muscles with- and without skin) affected the fatty acid profile and lipid indices. The sum of SFA was higher in S-V, M, and S samples for both kinds of meat than in raw ones. The cooked samples with skin had a lower percentage of Æ© SFA than the skinless meat. S-V and M cooking (for meat with skin) caused an increase, while in the case of S heating (for both kinds of meat) there were no significant differences in Æ© MUFA compared to raw samples. The S-V, M, and S meat with skin was characterized by a higher value of Æ© MUFA than skinless ones. The Æ© PUFA was lower in S-V and M than in raw meat, wherein this decline was higher for M ones (for both kinds of meat). The M meat with skin had the lowest and S without skin the highest share of Σ PUFA. Heat treatment caused an increase in Σ PUFA n-6/n-3 ratio, the lowest value was shown by the S-V muscles. Sous-vide cooking was more beneficial for consumers than the remaining methods in terms of Σ DFA/Σ OFA, Σ UFA/Σ SFA, NVI, health-promoting index (HPI), inflammatory biomarker indexes, and Σ SFA, Σ OFA, Σ UFA, Σ DFA values for meat with skin (but not all of these were significant). In turn, stewing of meat without skin was more favorable than S-V and microwave cooking in relation to indexes such as: Σ DFA/Σ OFA, Σ UFA/Σ SFA, Σ PUFA/Σ SFA, PI, UI, AI, TI, HPI.

Impact of frozen storage on fatty acid profile in goose meat.

The objective of this study was to investigate the changes of the fatty acid in breast (BM) and leg (LM) muscles from 17-wk-old female White Koluda geese packaged in a vacuum and stored in freezing conditions at -20°C. During 17 weeks, the geese were fed ad libitum on the same complete feed. The samples (18 LM and 18 BM) from the right part of the carcasses were stored for 30, 90, 80, 270, and 365 d. The changes in the fatty acid profile were established by gas chromatography. In this work, there were also calculated lipid profile indicators such as Σ PUFA n-6/Σ PUFA n-3, Σ UFA/Σ SFA, and Σ PUFA/Σ SFA. Time of frozen storage affected the decrease in Σ SFA, Σ MUFA, and Σ PUFA of BM and LM. The statistical analysis of the obtained data shows that the type of muscle also generally affected the fatty acid profile. The BM are characterized higher proportion of Σ SFA, and the LM are defined as containing more Σ MUFA and Σ PUFA. Extending frozen storage time caused only the deterioration of Σ PUFA n-6/Σ PUFA n-3. The Σ PUFA n-6/Σ PUFA n-3 were the highest in BM and LM on the 365th day of storage. Although the Σ PUFA n-6/Σ PUFA n-3 ratio in muscles stored for 180, 270, and 365 d was higher than the recommended values. The lipid profile indicators (Σ UFA/Σ SFA, and Σ PUFA/Σ SFA) were similar in raw meat and in all frozen storage samples. It means that frozen storage didn't affect this index and the BM and LM have the same quality from the dietary point of view. Leg muscles during frozen storage are characterized by higher Σ UFA/Σ SFA and Σ PUFA/Σ SFA than the breast muscles.

Impact of frozen storage on oxidation changes of some components in goose meat.

The objective of this study was to investigate the oxidation activity and lipid oxidation changes in breast (BM) and leg (LM) muscles from 17-wk-old female White Koluda geese packaged in a vacuum, and stored in freezing conditions at -20°C. The geese were fed ad libitum during the experimental period (up to 17 wk) on the same complete feed. The samples of LM (n = 18) and BM (n = 18) from the right carcass were stored for 30, 90, 80, 270, and 365 d. Lipid oxidation was described by determining changes in: TBARS value expressing the amount of malondialdehyde (MDA), total antioxidant capacity (TAC) measured by DPPH and ABTS methods and total reduction potential (TRP) measured by FRAP method. Moreover, total heam pigments pigment (THP), relative concentration of myoglobin (Mb), oxymyoglobin (MbO2), and metmyoglobin (MMb) were determined in this study. Time of storage affected the TAC, TRP, TBARS, and the color stability of BM and LM. The THP concentration and Mb proportion decrease gradually during the 365 d of frozen storage, while the relative concentration of MMb increase in BM and LM. It was noted that the shares of MMb in both analyzed types of muscles stored for 365 d did not exceed 0.4. This value is considered to be the limit, after which the meat takes on an intense gray-brown color not accepted by the consumer. The oxidation processes occurring during frozen storage caused an increase of TBARS and a decrease of DPPH•, ABTS•+, FRAP values in both kinds of muscles. The amounts of TBARS during frozen storage of muscles did not exceed 2.0 mg MDA/kg of meat. A higher value of TBARS than 2.0 causes a lack of acceptance by consumers of the flavor profile. Based on the results concerning changes in the heam pigments, as well as changes related to the oxidation of lipids, we cannot unequivocally state in which types of muscles the changes had a more intense course.

Fatty acid profile and health lipid indicies of goose meat in relation to various types of heat treatment.

The effect of water bath cooking (WBC), oven convection roasting (OCR), grilling (G), pan-frying (PF) on the fatty acid profile and health lipid indices of goose meat was investigated in this study. The experimental material covered 80 breast muscles (40 with skin and subcutaneous fat and 40 without skin) cut from carcasses of 17-week-old "Polish oat geese". The fatty acid profile of meat was determined by gas chromatography and health lipid indices were calculated. It was stated that the kind of heat treatment as well as the type of goose meat (muscles with and without skin) affected the fatty acid profile and health lipid indices. The sum of SFA was significantly higher in cooked samples for both kinds of meat than in raw ones. The cooked samples with skin had a lower increase in Æ© SFA than the skinless meat. Boiling (meat without skin) and pan-frying (both kinds of meat) caused a slight decrease, while grilling and oven convection roasting (both kinds of meat) caused an increase of Æ© MUFA in comparison to raw samples. Moreover, meat with skin is characterized by a higher value of Æ© MUFA than meat without skin for all cooking methods. The Æ© PUFA was lower in all cooked samples than in raw meat, wherein this decline was usually higher for skinned meat. The G meat was the lowest and PF the highest in Σ PUFA for both kinds of meat after heat treatment. The highest loss showed C20:4 n-6 in OCR samples and the lowest C18:2 n-6 in PF (both kinds of meat). Heat treatment caused an increase in the Σ PUFA n-6/n-3 ratio, wherein the lowest value was shown by the WBC samples without skin, and the highest by OCR with skin. Water bath cooking of meat was more beneficial for consumers in terms of AI, TI, Σ DFA/Σ OFA, Σ PUFA/Σ SFA, Σ UFA/Σ SFA indexes and Σ SFA, Σ OFA values than the remaining methods.

The selected goose meat quality traits in relation to various types of heat treatment.

The effect of water bath cooking (WBC), oven convection roasting (OCR), grilling (G), pan frying (PF) on selected physical properties of goose meat was compared in this study. A measurement of cooking loss, texture, color parameters, and sensory evaluation was carried out. The experimental material covered 96 breast muscles cut from carcasses of 17-week-old "Polish oat geese." The kind of goose meat (with and without skin) and the type of heat treatment affected cooking loss, shear force (SF), and rheological parameters (hardness, cohesiveness, gumminess, and chewiness). The water bath-cooked and pan-fried samples for both kinds of meat were characterized by lower cooking loss than other ones. Goose meat with skin and subcutaneous fat showed higher cooking loss and lower SF value, hardness, gumminess, and chewiness than that without skin for all methods. The water bath-cooked samples were characterized by the lowest SF value, hardness, and chewiness for both kinds of meat. They had the highest value of L∗ parameter and were characterized by a lighter color among others, too. Pan-fried meat showed the highest value of a∗ and lowest of ho parameters; the color of these samples was redder. Moreover, the lower C values of oven convection-roasted and grilled samples showed that they were brighter. According to the Comission Internationale de l'Eclairage classification, the ΔE parameter only for G and OCR indicated noticeable color differences (<2), whereas other pairs had visible differences. The method of cooking affected sensory descriptors such as the intensity of flavor and aroma, tenderness, juiciness, springiness, cohesiveness, and overall palatability of goose meat. The goose samples of PF, G, and OCR were characterized as very good and WBC as extremely desirable overall palatability. However, in the next stage of research, there is a need to study changes in the chemical composition, the degree of lipid oxidation, and the nutritional value of this meat that underwent different methods of cooking. Only then it will be possibly to clearly determine which method of the heat treatment of goose meat is optimal.

Lipid oxidation and color changes of goose meat stored under vacuum and modified atmosphere conditions.

The objective of the work was to investigate the color and lipid oxidation changes of goose breast meat packaged in vacuum and modified atmosphere (MA) conditions consisting of 80% O2, 20% CO2, and stored in refrigerated conditions at 4°C. Color stability was monitored by determining total heme pigments concentration; relative concentration of myoglobin, oxymyoglobin, and metmyoglobin; parameters of color L*, a*, b*, and sensory evaluation of the surface color. Lipid stability was measured by determining thiobarbituric acid reactive substances (TBARS). The samples were examined in 24 h after slaughter (unpacked muscles) and on d 4, 7, 9, 11 of storage (muscles packed in vacuum and in MA). Through the time of storage, samples packed in MA had higher TBARS values in comparison to the meat packed in vacuum. For samples packed in two types of atmospheres, the total pigments concentration decreased gradually within 11 d of storage. It was observed that relative metmyoglobin concentration increased whereas relative oxymyoglobin concentration decreased in total heme pigments in the MA stored muscle. The relative concentration of all three myoglobin forms sample packed in vacuum remained unchanged. The color parameters (L*, a*, b*) did not change for 11 d of storage for the vacuum packed meat. The value of the color parameter a* decreased and the value of the color parameters L* and b* increased in the samples packaged in MA. The data prove that if you store goose meat in MA (consisting of 80% O2, 20% CO2) or vacuum, the unchanged surface color is preserved for 9 and 11 day, respectively.Vacuum appears to be a better method as regards the maintaining of lipid stability in goose meat.

Antibodies to recombinant fragment 212-276 of protein C specifically recognize the intact human molecule.

The peptide fragment Pro212-Ile276 of human protein C was produced as a part of a fusion protein in Escherichia coli. The identity of the peptide was confirmed by immunoblotting experiments using specific antibodies to intact protein C. The peptide Pro212-Ile276 was isolated from the fusion protein after mild hydrolysis with formic acid by gel filtration and reverse-phase HPLC. This peptide fragment was used to produce antibodies specific for the heavy chain of protein C which recognized native protein C present in blood plasma. Antibodies to intact protein C reacted also with the Pro212-Ile276 peptide fragment, indicating that this region is immunogenic in intact protein C and may represent a native epitope.

Modulation of plasminogen activator inhibitor type-1 biosynthesis in vitro and in vivo with oligo(nucleoside phosphorothioate)s and related constructs.

Oligonucleotides with a nucleotide sequence complementary to various regions of human plasminogen activator inhibitor type-1 (PAI-1) mRNA have been studied as antisense inhibitors of expression of PAI-1 protein in cultured cells [human umbilical vein endothelial cells (HUVEC), human aortic smooth muscle cells, human hybrid endothelial cells]. Hexadeca(deoxyribonucleoside phosphorothioate) 13 complementary to a fragment of a signal peptide PAI-1 mRNA was found to be most active, giving ca. 70% inhibition of PAI-1 release in a time- and dose-dependent way. The stereo-regular All-S(P) and All-R(P) diastereomers of 13 were studied and found to inhibit PAI-1 synthesis in HUVEC in a stereo-dependent manner, with the All-S(P) diastereomer considerably more active than the stereo-random construct and All-R(P) isomer. The observed stereo-dependent activity of oligonucleotide phosphorothioate constructs is presumably governed by their resistance to nucleases. The corresponding phosphodiester analogue of 13 was not active unless covalently bound at its 5'-end to a lipophilic alcohol residue (menthol, heptadecanol). The observed antisense activity of phosphodiester oligonucleotide bioconjugates in cultured human hybrid endothelial cells was paralleled by their increased stability in human plasma with respect to unconjugated oligonucleotide. The oligo(deoxyribonucleoside phosphorothioate) complementary to the same signal peptide region of rat PAI-1 mRNA was found to reduce the PAI-1 level in blood plasma of rats after intravenous administration into the tail vein. The effect was both time- and dose-dependent. The same oligonucleotide was found to protect against arterial thrombus formation in the rat (lower incidence of venous thrombosis, lower thrombus weight, and increased occlusion time in experimentally induced thrombosis). An anti-PAI-1 inhibitory activity has been independently reported for a 20-mer oligo(2'-O-methyl-ribonucleoside phosphorothioate) complementary to a 3'-untranslated region of human PAI-1 mRNA in cultured HUVEC and human aortic smooth muscle cells.

Synthesis of a gene encoding bovine substance P precursors and its expression in Escherichia coli.

Using an efficient Escherichia coli expression system, we have been able to obtain the precursor of substance P, alpha-preprotachykinin (alpha PPT). The alpha PPT protein is produced in E. coli as a fusion to beta-galactosidase, and accumulates in the cytoplasm as insoluble inclusion bodies. We also produced protachykinin (alpha PT), i.e., alpha PPT without a signal peptide. Further purification and characterization of the alpha PPT and alpha PT polypeptides strongly suggest that fully purified products can be obtained using our procedures.

The synthesis of nucleoside 5'-O-(1,1-dithiotriphosphates).

Appropriately protected nucleoside 5'-O-(2-thio-1,3,2-dithiaphospholanes) react with inorganic pyrophosphate in the presence of a strong base catalyst (DBU) to give nucleoside 5'-O-(1,1-dithiotriphosphates) 1a-g. The latter compounds, including an AZT analogue, show modest antivirial activity against HIV-1 and HIV-2 replication in CEM cells. The AZT and deoxyadenosine derivatives were found to be inhibitors of HIV reverse transcriptase.

2',3'-Bis(2-chloroethyl)aminophosphoryl-3'-amino-3'-deoxyadenosine: a cyclic nucleotide with antitumor activity.

The synthesis of the title compound from 3'-amino-3'-deoxyadenosine in 40% yield is reported. 3'-Amino-3'-deoxyadenosine was made by an improved synthesis in 12 steps from inexpensive D-xylose in 15% overall yield. Both isomers of the title compound, separated by column chromatography, possess confirmed activity against KB tumor cell cultures.

Stereospecific synthesis of chiral metabolites of ifosfamide and their determination in the urine.

The stereospecific synthesis of two chiral metabolites of ifosfamide (2), 4-ketoifosfamide (5) and 2-amino-3-(2-chloroethyl)tetrahydro-2H-1,3, 2-oxazaphosphorine 2-oxide (9), is reported. The absolute configuration of both compounds was assigned on the basis of chemical correlation. In addition, two other achiral metabolites of 2, carboxyifosfamide (6) and IPAM (7), were synthesized. These and other organophosphorus metabolites of ifosfamide were found, by 31P NMR, in the urine of patients to whom racemic 2 was administered. The measurements performed in the presence of optically active lanthanide shift reagent [Eu(tfc)3] showed considerable stereoselectivity of in vivo formation of some chiral metabolites of ifosfamide.

Phosphorothioate oligodeoxyribonucleotides antisense to PAI-1 mRNA increase fibrinolysis and modify experimental thrombosis in rats.

The effect of systemic inhibition of PAI-1 expression in rats by PS-16R, a phosphorothioate analogue of hexadecadeoxyribonucleotide complementary to a signal peptide coding sequence of rat PAI-1 mRNA, on PAI-1 activity in blood plasma and thrombus formation was studied in rat models for experimental thrombosis. In previous in vitro studies, oligonucleotides of PS-16R family have been shown to inhibit efficiently PAI-1 synthesis in endothelial cells by antisense mechanism. When PS-16R was administered intravenously as a single bolus injection (1 to 5 mg per rat), it produced a significant reduction in PAI-1 activity of blood plasma. This effect was both time- and concentration-dependent. Under the same conditions, three groups of rats were treated with control oligodeoxynucleotides such as PS-16R with double mismatches, with scrambled sequence, and an oligodeoxynucleotide with sense sequence (complementary to PS-16R), respectively. Based on these preliminary experiments, a low dose of 1.5 mg per rat was selected to produce approximately 20-30% reduction of PAI-1 activity in blood plasma and the effect of such a decrease in PAI-1 expression was tested on thrombus formation in two rat models for experimentally induced thrombosis. Such a limited decrease in PAI-1 activity produced a significant antithrombotic effect in the arterial thrombosis model. There was a profound delay in the occlusion time in rats treated with PS-16R when compared to control animals (80 +/- 3 and 55 +/- 3 h, respectively), although blood plasma activity of PAI-1 in the same groups of rats differed only by 20%. There was also a tendency to reduce both an incidence of venous thrombosis (58.33 and 68.11%, respectively) and thrombus weight (2.1 +/- 0.4 and 2.9 +/- 0.9 mg, respectively) in the animals treated with PS-16R. However, this effect was not significant. Thus, low dose of PS-16R through inhibition of PAI-1 synthesis in targeted cells in rats reduced PAI-1 activity in blood plasma and protected against arterial thrombus formation in the rat.

Diastereomers of thymidine 3'-O-(methanephosphonothioate): synthesis, absolute configuration and reaction with 3'-methoxyacetylthymidine under conditions of triester approach to oligonucleotide synthesis.

Diastereomers of the title compound were obtained and absolute configuration was assigned by means of stereochemical correlation. Their reaction with 3'-O-methoxyacetylthymidine in the presence of triisopropylbenzenesulphonyl (4-nitro) triazole is neither chemo- nor stereo-selective and leads to diastereomeric pairs of dithymidyl (3',5')methanephosphonate and -methanephosphonothioate. Obtained results are discussed in terms of mechanism of activation of phosphodiesters under conditions known as "phosphotriester approach to oligonucleotide synthesis".

Synthesis and interaction with thymidylate synthase of 5'-dithiophosphate and 5'-fluorothiophosphate of thymidine.

Thymidine-5'-fluorothiophosphate, dTMP(S)-F, was synthesized by the oxathiaphospholane, and thymidine 5'-dithiophosphate, dTMPS2, by the dithiaphospholane, method. To estimate the role of 5'-phosphate group ionization in binding of pyrimidine nucleotides by thymidylate synthase, dTMP(S)-F was studied as an inhibitor of mouse tumour (L1210) enzyme, and its inhibitory properties were compared with those of dTMPS2, a close dTMP analogue. While dTMPS2 proved to be an inhibitor, competitive vs dUMP, with K(i)app = 94 microM, the 5'-fluorothiophosphate congener displayed no activity, indicating that the enzyme requires for binding the presence of a dianionic 5'-phosphate group in a nucleotide.

The epidermal growth factor-like domain from tissue plasminogen activator. Cloning in E. coli, purification and ESR studies of its interaction with human blood platelets.

To examine whether the epidermal growth factor (EGF)-like domain Pro47-Asp87 is involved in the interaction of tissue plasminogen activator (t-PA) with platelets, we have expressed this domain in E. coli. The peptide fragment was produced from a plasmid expression vector as a fusion protein with beta-galactosidase Met1-Val444 at high yield in eight clones of E. coli. The fusion protein was purified and subjected to mild acid hydrolysis with formic acid, then the peptide Pro47-Asp87, identified by immunoblotting using specific antibodies to t-PA, was isolated by HPLC. After incubation with blood platelets spin labelled with 16-doxylstearic acid or 5-doxylstearic acid, the Pro47-Asp87 peptide fragment reduced fluidity of the membrane lipid bilayer to the same extent as did intact t-PA as indicated by ESR measurements. Our data suggest that the EGF-like domain of t-PA can directly interact with blood platelets and thus it seems to contain those sites of the t-PA molecule that bind the platelet membrane components.

Inhibition of plasminogen activator inhibitor release in endothelial cell cultures by antisense oligodeoxyribonucleotides with a 5'-end lipophilic modification.

A series of conjugates containing residues of lipophilic alcohols covalently bound to 5' end of oligodeoxyribonucleotides targeted against human plasminogen activator inhibitor (PAI-1) mRNA was synthesized via the oxathiaphospholane approach. The highest anti-PAI-1 activity in EA.hy 926 endothelial cell cultures was found for conjugates containing menthyl or heptadecanyl groups linked with an oligonucleotide complementary to a segment of human PAI-1 mRNA. The phosphodiester antisense oligonucleotides, which otherwise exhibit only limited anti-PAI-1 activity, were found to be more active than phosphorothioate oligonucleotides when conjugated to lipophilic alcohol residues. For menthyl conjugates an evidence of antisense mechanism of inhibition was found.