64 research outputs found
Noncovalent microarrays from synthetic amino-terminating glycans: Implications in expanding glycan microarray diversity and platform comparison
Glycan microarrays have played important roles in detection and specificity assignment of glycan recognition by proteins. However, the size and diversity of glycan libraries in current microarray systems are small compared to estimated glycomes, and these may lead to missed detection or incomplete assignment. For microarray construction, covalent and noncovalent immobilization are the two types of methods used, but a direct comparison of results from the two platforms is required. Here we develop a chemical strategy to prepare lipid-linked probes from both naturally derived aldehyde-terminating and synthetic amino-terminating glycans that addresses the two aspects: expansion of sequence-defined glycan libraries and comparison of the two platforms. We demonstrate the specific recognition by plant and mammalian lectins, carbohydrate-binding modules and antibodies and the overall similarities from the two platforms. Our results provide new knowledge on unique glycan-binding specificities for the immune receptor Dectin-1 toward Ξ²-glucans and the interaction of rotavirus P[19] adhesive protein with mucin O-glycan cores
Π‘ΡΠ°Π²Π½ΠΈΡΠ΅Π»ΡΠ½ΠΎΠ΅ ΠΈΠ·ΡΡΠ΅Π½ΠΈΠ΅ Π°Π½ΡΠΈΠΈΡΠ΅ΠΌΠΈΡΠ΅ΡΠΊΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΡΡΠΈΠΌΠ΅ΡΠ°Π·ΠΈΠ΄ΠΈΠ½Π° ΠΈ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ ΠΠΠ-802 Π² ΡΡΠ»ΠΎΠ²ΠΈΡΡ ΡΠ½Π΄ΠΎΡΠ΅Π»ΠΈΠ°Π»ΡΠ½ΠΎΠΉ Π΄ΠΈΡΡΡΠ½ΠΊΡΠΈΠΈ
Resume. Methods. Acute subendocardial myocardial ischemia in anesthetized rats (urethane 1300 mg/kg, i.p.) was caused by isoproterenol (20 |jg/kg/ min, i.v.). Endothelial dysfunction was induced, causing hyperhomocysteinemia in rats (methionine 3 g/kg intragastrically 1 time per day for 7 days). The aim. To study on the subendocardial ischemia model in rats the peculiarities of the anti-ischemic action of p-FOX inhibitor trimetazidine and trihydrochloride N1-(2,3,4-trimethoxybenzyl)-N2-{2-[(2,3,4-trimethoxybenzyl)amino]ethyl}-1,2-ethanediamine constructed on the basis of its structure (compound ALM-802) under conditions of endothelial dysfunction. Results. It was shown that in rats with an intact vascular bed and the reference drug trimetazidine (30 mg/kg, i.v.) and the compound ALM-802 (2 mg/kg, i.v.) demonstrated pronounced anti-ischemic activity, while in animals with endothelial dysfunction only the compound ALM-802 was effective. Conclusion. Endothelial dysfunction prevents the implementation of the trimetazidine anti-ischemic action, but does not affect on the compound ALM-802 effect. When studying the anti-ischemic properties of new pharmacological substances, it is advisable to carry out a certain part of the experiments in model experiments that reproduce endothelial dysfunction.Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ. ΠΠ·ΡΡΠΈΡΡ Π½Π° ΠΌΠΎΠ΄Π΅Π»ΠΈ ΡΡΠ±ΡΠ½Π΄ΠΎΠΊΠ°ΡΠ΄ΠΈΠ°Π»ΡΠ½ΠΎΠΉ ΠΈΡΠ΅ΠΌΠΈΠΈ Ρ ΠΊΡΡΡ ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠΈ Π°Π½ΡΠΈΠΈΡΠ΅ΠΌΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ p-FOX ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΠ° ΡΡΠΈΠΌΠ΅ΡΠ°Π·ΠΈΠ΄ΠΈΠ½Π° ΠΈ ΡΠΊΠΎΠ½ΡΡΡΡΠΈΡΠΎΠ²Π°Π½Π½ΠΎΠ³ΠΎ Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ Π΅Π³ΠΎ ΡΡΡΡΠΊΡΡΡΡ ΡΡΠΈΠ³ΠΈΠ΄ΡΠΎΡ
Π»ΠΎΡΠΈΠ΄ N1-(2,3,4-ΡΡΠΈΠΌΠ΅ΡΠΎΠΊΡΠΈΠ±Π΅Π½Π·ΠΈΠ»)-N2-{2-[(2,3,4-ΡΡΠΈΠΌΠ΅ΡΠΎΠΊΡΠΈΠ±Π΅Π½Π·ΠΈΠ»)Π°ΠΌΠΈΠ½ΠΎ]ΡΡΠΈΠ»}-1,2-ΡΡΠ°Π½Π΄ΠΈΠ°ΠΌΠΈΠ½Π° (ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠ΅ ΠΠΠ-802) Π² ΡΡΠ»ΠΎΠ²ΠΈΡΡ
ΡΠ½Π΄ΠΎΡΠ΅Π»ΠΈΠ°Π»ΡΠ½ΠΎΠΉ Π΄ΠΈΡΡΡΠ½ΠΊΡΠΈΠΈ. ΠΠ°ΡΠ΅ΡΠΈΠ°Π» ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. ΠΡΡΡΡΡ ΡΡΠ±ΡΠ½Π΄ΠΎΠΊΠ°ΡΠ΄ΠΈΠ°Π»ΡΠ½ΡΡ ΠΈΡΠ΅ΠΌΠΈΡ ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π° Ρ Π½Π°ΡΠΊΠΎΡΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΠΊΡΡΡ (ΡΡΠ΅ΡΠ°Π½ 1300 ΠΌΠ³/ΠΊΠ³, Π²/Π±) Π²ΡΠ·ΡΠ²Π°Π»ΠΈ ΠΏΡΡΡΠΌ ΠΈΠ½ΡΡΠ·ΠΈΠΈ ΠΈΠ·ΠΎΠΏΡΠΎΡΠ΅ΡΠ΅Π½ΠΎΠ»Π° (20 ΠΌΠΊΠ³/ΠΊΠ³/ΠΌΠΈΠ½, Π²/Π²). ΠΠ½Π΄ΠΎΡΠ΅Π»ΠΈΠ°Π»ΡΠ½ΡΡ Π΄ΠΈΡΡΡΠ½ΠΊΡΠΈΡ ΠΈΠ½Π΄ΡΡΠΈΡΠΎΠ²Π°Π»ΠΈ, Π²ΡΠ·ΡΠ²Π°Ρ Ρ ΠΊΡΡΡ Π³ΠΈΠΏΠ΅ΡΠ³ΠΎΠΌΠΎΡΠΈΡΡΠ΅ΠΈΠ½Π΅ΠΌΠΈΡ (ΠΌΠ΅ΡΠΈΠΎΠ½ΠΈΠ½ 3 Π³/ΠΊΠ³ Π²Π½ΡΡΡΠΈΠΆΠ΅Π»ΡΠ΄ΠΎΡΠ½ΠΎ 1 ΡΠ°Π· Π² ΡΡΡΠΊΠΈ Π² ΡΠ΅ΡΠ΅Π½ΠΈΠ΅ 7 Π΄Π½Π΅ΠΉ). Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ Ρ ΠΊΡΡΡ Ρ ΠΈΠ½ΡΠ°ΠΊΡΠ½ΡΠΌ ΡΠΎΡΡΠ΄ΠΈΡΡΡΠΌ ΡΡΡΠ»ΠΎΠΌ ΠΈ ΡΡΠ°Π»ΠΎΠ½Π½ΡΠΉ ΠΏΡΠ΅ΠΏΠ°ΡΠ°Ρ ΡΡΠΈΠΌΠ΅ΡΠ°Π·ΠΈΠ΄ΠΈΠ½ (30 ΠΌΠ³/ΠΊΠ³, Π²/Π²), ΠΈ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠ΅ ΠΠΠ-802 (2 ΠΌΠ³/ΠΊΠ³, Π²/Π²) ΠΏΡΠΎΡΠ²Π»ΡΡΡ Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΡΡ Π°Π½ΡΠΈΠΈΡΠ΅ΠΌΠΈΡΠ΅ΡΠΊΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ, ΡΠΎΠ³Π΄Π° ΠΊΠ°ΠΊ Ρ ΠΆΠΈΠ²ΠΎΡΠ½ΡΡ
Ρ ΡΠ½Π΄ΠΎΡΠ΅Π»ΠΈΠ°Π»ΡΠ½ΠΎΠΉ Π΄ΠΈΡΡΡΠ½ΠΊΡΠΈΠ΅ΠΉ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎ ΡΠΎΠ»ΡΠΊΠΎ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠ΅ ΠΠΠ-802. ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΠ½Π΄ΠΎΡΠ΅Π»ΠΈΠ°Π»ΡΠ½Π°Ρ Π΄ΠΈΡΡΡΠ½ΠΊΡΠΈΡ ΠΏΡΠ΅ΠΏΡΡΡΡΠ²ΡΠ΅Ρ ΡΠ΅Π°Π»ΠΈΠ·Π°ΡΠΈΠΈ Π°Π½ΡΠΈΠΈΡΠ΅ΠΌΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ ΡΡΠΈΠΌΠ΅ΡΠ°Π·ΠΈΠ΄ΠΈΠ½Π°, Π½ΠΎ Π½Π΅ Π²Π»ΠΈΡΠ΅Ρ Π½Π° ΡΠ°ΠΊΠΎΠ²ΠΎΠ΅ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ ΠΠΠ-802. ΠΡΠΈ ΠΈΠ·ΡΡΠ΅Π½ΠΈΠΈ Π°Π½ΡΠΈΠΈΡΠ΅ΠΌΠΈΡΠ΅ΡΠΊΠΈΡ
ΡΠ²ΠΎΠΉΡΡΠ² Π½ΠΎΠ²ΡΡ
ΡΠ°ΡΠΌΠ°ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ
Π²Π΅ΡΠ΅ΡΡΠ² ΠΎΠΏΡΠ΅Π΄Π΅Π»ΡΠ½Π½ΡΡ ΡΠ°ΡΡΡ ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠΎΠ² ΡΠ΅Π»Π΅ΡΠΎΠΎΠ±ΡΠ°Π·Π½ΠΎ ΠΏΡΠΎΠ²ΠΎΠ΄ΠΈΡΡ Π² ΠΌΠΎΠ΄Π΅Π»ΡΠ½ΡΡ
ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Ρ
, Π²ΠΎΡΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄ΡΡΠΈΡ
ΡΠ½Π΄ΠΎΡΠ΅Π»ΠΈΠ°Π»ΡΠ½ΡΡ Π΄ΠΈΡΡΡΠ½ΠΊΡΠΈΡ
ΠΠ°ΡΠ΄ΠΈΠΎΠΏΡΠΎΡΠ΅ΠΊΡΠΎΡΠ½ΡΠ΅ ΡΡΡΠ΅ΠΊΡΡ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ ΠΠΠ-802 Π½Π° ΠΌΠΎΠ΄Π΅Π»ΡΡ ΡΡΠ±ΡΠ½Π΄ΠΎΠΊΠ°ΡΠ΄ΠΈΠ°Π»ΡΠ½ΠΎΠΉ ΠΈΡΠ΅ΠΌΠΈΠΈ
The investigation purpose. N1-(2,3,4-trimethoxybenzyl)-N2-{2-[(2,3,4-trimethoxybenzyl)amino]ethyl}-1,2-ethanediamine (ALM-802 compounds) cardioprotective effect has been studied in rat models of subendocardial ischemia caused by isoproterenol and dobutamine. Material and methods. Acute subendocardial myocardial ischemia in anesthetized rats (urethane 1300 mg/kg, i.p.) was caused by infusion of isoproterenol (20 Β΅g/kg/min i.v.) or dobutamine (80 Β΅g/kg/min i.v.). Results. It was shown that in anesthetized rats, isoproterenol and dobutamine caused almost the same ST-segment depression in the II standard ECG lead. The compound ALM-802 (2 mg/kg i.v.), administered 2 minutes before the infusion start of isoproterenol or dobutamine, equally prevented the occurrence of ischemic changes on the ECG. Conclusion. The non-selective beta-adrenomimetic isoproterenol and the selective Ξ²1-adrenomimetic dobutamine cause subendocardial ischemia of the same intensity in anesthetized rats. The compound ALM-802 has a pronounced anti-ischemic effect on both models.Π¦Π΅Π»Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ. ΠΠ·ΡΡΠΈΡΡ Π² ΡΡΠ°Π²Π½ΠΈΡΠ΅Π»ΡΠ½ΠΎΠΌ Π°ΡΠΏΠ΅ΠΊΡΠ΅ ΠΊΠ°ΡΠ΄ΠΈΠΎΠΏΡΠΎΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΠ΅ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ N1-(2,3,4-ΡΡΠΈΠΌΠ΅ΡΠΎΠΊΡΠΈΠ±Π΅Π½Π·ΠΈΠ»)-N2-{2-[(2,3,4- ΡΡΠΈΠΌΠ΅ΡΠΎΠΊΡΠΈΠ±Π΅Π½Π·ΠΈΠ»)Π°ΠΌΠΈΠ½ΠΎ]ΡΡΠΈΠ»}-1,2-ΡΡΠ°Π½Π΄ΠΈΠ°ΠΌΠΈΠ½Π° (ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ ΠΠΠ-802) Π½Π° ΠΌΠΎΠ΄Π΅Π»ΡΡ
ΡΡΠ±ΡΠ½Π΄ΠΎΠΊΠ°ΡΠ΄ΠΈΠ°Π»ΡΠ½ΠΎΠΉ ΠΈΡΠ΅ΠΌΠΈΠΈ Ρ ΠΊΡΡΡ, Π²ΡΠ·ΡΠ²Π°Π΅ΠΌΠΎΠΉ ΠΈΠ·ΠΎΠΏΡΠΎΡΠ΅ΡΠ΅Π½ΠΎΠ»ΠΎΠΌ ΠΈ Π΄ΠΎΠ±ΡΡΠ°ΠΌΠΈΠ½ΠΎΠΌ. ΠΠ°ΡΠ΅ΡΠΈΠ°Π» ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ. ΠΡΡΡΡΡ ΡΡΠ±ΡΠ½Π΄ΠΎΠΊΠ°ΡΠ΄ΠΈΠ°Π»ΡΠ½ΡΡ ΠΈΡΠ΅ΠΌΠΈΡ ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π° Ρ Π½Π°ΡΠΊΠΎΡΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΠΊΡΡΡ (ΡΡΠ΅ΡΠ°Π½ 1300 ΠΌΠ³/ΠΊΠ³, Π²/Π±) Π²ΡΠ·ΡΠ²Π°Π»ΠΈ ΠΏΡΡΡΠΌ ΠΈΠ½ΡΡΠ·ΠΈΠΈ ΠΈΠ·ΠΎΠΏΡΠΎΡΠ΅ΡΠ΅Π½ΠΎΠ»Π° (20 ΠΌΠΊΠ³/ΠΊΠ³/ΠΌΠΈΠ½, Π²/Π²) ΠΈΠ»ΠΈ Π΄ΠΎΠ±ΡΡΠ°ΠΌΠΈΠ½Π° (80 ΠΌΠΊΠ³/ΠΊΠ³/ΠΌΠΈΠ½, Π²/Π²). Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ. ΠΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ Ρ Π½Π°ΡΠΊΠΎΡΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΠΊΡΡΡ ΠΈΠ·ΠΎΠΏΡΠΎΡΠ΅ΡΠ΅Π½ΠΎΠ» ΠΈ Π΄ΠΎΠ±ΡΡΠ°ΠΌΠΈΠ½ Π²ΡΠ·ΡΠ²Π°ΡΡ ΠΏΡΠ°ΠΊΡΠΈΡΠ΅ΡΠΊΠΈ ΠΎΠ΄ΠΈΠ½Π°ΠΊΠΎΠ²ΡΡ Π΄Π΅ΠΏΡΠ΅ΡΡΠΈΡ ΡΠ΅Π³ΠΌΠ΅Π½ΡΠ° ST Π²ΠΎ II ΡΡΠ°Π½Π΄Π°ΡΡΠ½ΠΎΠΌ ΠΎΡΠ²Π΅Π΄Π΅Π½ΠΈΠΈ ΠΠΠ. Π‘ΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠ΅ ΠΠΠ-802 (2 ΠΌΠ³/ΠΊΠ³ Π²/Π²), Π²Π²Π΅Π΄ΡΠ½Π½ΠΎΠ΅ Π·Π° 2 ΠΌΠΈΠ½ Π΄ΠΎ Π½Π°ΡΠ°Π»Π° ΠΈΠ½ΡΡΠ·ΠΈΠΈ ΠΈΠ·ΠΎΠΏΡΠΎΡΠ΅ΡΠ΅Π½ΠΎΠ»Π° ΠΈΠ»ΠΈ Π΄ΠΎΠ±ΡΡΠ°ΠΌΠΈΠ½Π°, Π² ΡΠ°Π²Π½ΠΎΠΉ ΡΡΠ΅ΠΏΠ΅Π½ΠΈ ΠΏΡΠ΅Π΄ΠΎΡΠ²ΡΠ°ΡΠ°Π»ΠΎ Π²ΠΎΠ·Π½ΠΈΠΊΠ½ΠΎΠ²Π΅Π½ΠΈΠ΅ ΠΈΡΠ΅ΠΌΠΈΡΠ΅ΡΠΊΠΈΡ
ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠΉ Π½Π° ΠΠΠ. ΠΠ°ΠΊΠ»ΡΡΠ΅Π½ΠΈΠ΅. ΠΠ΅ΡΠ΅Π»Π΅ΠΊΡΠΈΠ²Π½ΡΠΉ Ξ²-Π°Π΄ΡΠ΅Π½ΠΎΠΌΠΈΠΌΠ΅ΡΠΈΠΊ ΠΈΠ·ΠΎΠΏΡΠΎΡΠ΅ΡΠ΅Π½ΠΎΠ» ΠΈ ΡΠ΅Π»Π΅ΠΊΡΠΈΠ²Π½ΡΠΉ Ξ²1-Π°Π΄ΡΠ΅Π½ΠΎΠΌΠΈΠΌΠ΅ΡΠΈΠΊ Π΄ΠΎΠ±ΡΡΠ°ΠΌΠΈΠ½ Π²ΡΠ·ΡΠ²Π°ΡΡ Ρ Π½Π°ΡΠΊΠΎΡΠΈΠ·ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΠΊΡΡΡ ΡΡΠ±ΡΠ½Π΄ΠΎΠΊΠ°ΡΠ΄ΠΈΠ°Π»ΡΠ½ΡΡ ΠΈΡΠ΅ΠΌΠΈΡ ΠΎΠ΄ΠΈΠ½Π°ΠΊΠΎΠ²ΠΎΠΉ ΠΈΠ½ΡΠ΅Π½ΡΠΈΠ²Π½ΠΎΡΡΠΈ. Π‘ΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠ΅ ΠΠΠ-802 ΠΎΠ±Π»Π°Π΄Π°Π΅Ρ Π²ΡΡΠ°ΠΆΠ΅Π½Π½ΡΠΌ ΠΏΡΠΎΡΠΈΠ²ΠΎΠΈΡΠ΅ΠΌΠΈΡΠ΅ΡΠΊΠΈΠΌ ΡΡΡΠ΅ΠΊΡΠΎΠΌ Π½Π° ΠΎΠ±Π΅ΠΈΡ
ΠΌΠΎΠ΄Π΅Π»ΡΡ
.
Toward a Prostate Specific Antigen-Based Prostate Cancer Diagnostic Assay: Preparation of Keyhole Limpet Hemocyanin -Conjugated Normal and Transformed Prostate Specific Antigen Fragments
Π‘ΠΊΡΠΈΠ½ΠΈΠ½Π³ ΠΊΠ°ΡΠ΄ΠΈΠΎΡΡΠΎΠΏΠ½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π² ΡΡΠ΄Ρ Ξ±, Ο-Π΄ΠΈΠ°ΡΠΈΠ»ΠΌΠ΅ΡΠΈΠ»ΡΠ½ΡΡ ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΡΡ Π±ΠΈΡ-(Ο-Π°ΠΌΠΈΠ½ΠΎΠ°Π»ΠΊΠΈΠ»)Π°ΠΌΠΈΠ½ΠΎΠ²
ΠΠΎΠΈΡΠΊ Π½ΠΎΠ²ΡΡ
ΠΎΡΠΈΠ³ΠΈΠ½Π°Π»ΡΠ½ΡΡ
ΠΊΠ°ΡΠ΄ΠΈΠΎΡΡΠΎΠΏΠ½ΡΡ
Π»Π΅ΠΊΠ°ΡΡΡΠ²Π΅Π½Π½ΡΡ
ΡΡΠ΅Π΄ΡΡΠ², ΠΎΠ±Π»Π°Π΄Π°ΡΡΠΈΡ
Π°Π½ΡΠ°ΡΠΊΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΈ Π°Π½ΡΠΈΠΈΡΠ΅ΠΌΠΈΡΠ΅ΡΠΊΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡΡ, Π±Π΅Π·ΡΡΠ»ΠΎΠ²Π½ΠΎ, ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΎΠ΄Π½ΠΎΠΉ ΠΈΠ· Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ Π°ΠΊΡΡΠ°Π»ΡΠ½ΡΡ
Π·Π°Π΄Π°Ρ, ΡΡΠΎΡΡΠΈΡ
ΠΏΠ΅ΡΠ΅Π΄ ΡΠΎΠ²ΡΠ΅ΠΌΠ΅Π½Π½ΠΎΠΉ ΠΊΠ°ΡΠ΄ΠΈΠΎΡΠ°ΡΠΌΠ°ΠΊΠΎΠ»ΠΎΠ³ΠΈΠ΅ΠΉ. Π ΡΠ°ΠΌΠΊΠ°Ρ
ΡΠ΅ΡΠ΅Π½ΠΈΡ ΡΡΠΎΠΉ ΠΏΡΠΎΠ±Π»Π΅ΠΌΡ Π²ΠΏΠ΅ΡΠ²ΡΠ΅ Π² ΡΡΠ΄Ρ Ξ±, Ο-Π΄ΠΈΠ°ΡΠΈΠ»ΠΌΠ΅ΡΠΈΠ»ΡΠ½ΡΡ
ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΡΡ
Π±ΠΈΡ- (Ο -Π°ΠΌΠΈΠ½ΠΎΠ°Π»ΠΊΠΈΠ») Π°ΠΌΠΈΠ½ΠΎΠ² Π±ΡΠ» ΠΏΡΠΎΠ²Π΅Π΄ΡΠ½ ΠΏΠΎΠΈΡΠΊ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ, ΠΎΠ±Π»Π°Π΄Π°ΡΡΠΈΡ
ΠΏΠΎΠ΄ΠΎΠ±Π½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡΡ
ΠΠΎΠΈΡΠΊ ΡΠ΅Π»Π΅ΠΊΡΠΈΠ²Π½ΡΡ Π±Π»ΠΎΠΊΠ°ΡΠΎΡΠΎΠ² ΡΠΈΠ½ΠΊ-Π·Π°Π²ΠΈΡΠΈΠΌΡΡ ΠΌΠ΅ΡΠ°Π»Π»ΠΎΠΏΡΠΎΡΠ΅ΠΈΠ½Π°Π· 2-Π³ΠΎ ΠΈ 9-Π³ΠΎ ΡΠΈΠΏΠ° Π² ΡΡΠ΄Ρ Π±Π΅Π½Π·ΠΎΠΈΠ»Π°ΠΌΠΈΠ½ΠΎ(ΡΠ΅Π½ΠΈΠ»ΡΡΠ»ΡΡΠΎΠ½ΠΈΠ»)-Π·Π°ΠΌΠ΅ΡΠ΅Π½Π½ΡΡ ΡΠΈΠΊΠ»ΠΈΡΠ΅ΡΠΊΠΈΡ Π°ΠΌΠΈΠ½ΠΎΠΊΠΈΡΠ»ΠΎΡ
The purpose of this study - search among the benzoylamino (phenyLsuLfonyL) amino-substituted cyclic aminoacids derivatives biologically active compounds exhibiting properties of the zinc-dependent metaLLproteinases 2nd and 9th type blockers which is known to pLay a key roLe in the pathogenesis of the myocardium earLy post-infarction remodeLing. In studying the effect of newLy synthesized compounds on metaLLoproteinase-9 LeveLs in bLood of rats with acute myocardiaL infarction were seLected compound Leader: 1-({4-[(4-chLorobenzoyL)amino]phenyL}suLfonyL-L-proLine, which effectiveLy bLocked the increase of this enzyme Level. Using echocardiography it was demonstrated that the seLected compound-Leader prevents the myocardiaL remodeLing deveLopment in the acute phase of experimentaL myocardiaL infarction, at Least not inferior to the reference inhibitor of metaLLoproteinases - doxycycLine.Π¦Π΅Π»Ρ Π½Π°ΡΡΠΎΡΡΠ΅Π³ΠΎ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ - ΠΏΠΎΠΈΡΠΊ Π² ΡΡΠ΄Ρ Π±Π΅Π½Π·ΠΎΠΈΠ»Π°ΠΌΠΈΠ½ΠΎ(ΡΠ΅Π½ΠΈΠ»ΡΡΠ»ΡΡΠΎΠ½ΠΈΠ»)-Π·Π°ΠΌΠ΅ΡΡΠ½Π½ΡΡ
ΡΠΈΠΊΠ»ΠΈΡΠ΅ΡΠΊΠΈΡ
Π°ΠΌΠΈΠ½ΠΎΠΊΠΈΡΠ»ΠΎΡ Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈ Π°ΠΊΡΠΈΠ²Π½ΡΡ
ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ, ΠΎΠ±Π»Π°Π΄Π°ΡΡΠΈΡ
ΡΠ²ΠΎΠΉΡΡΠ²Π°ΠΌΠΈ Π±Π»ΠΎΠΊΠ°ΡΠΎΡΠΎΠ², ΡΠΈΠ½ΠΊ-Π·Π°Π²ΠΈΡΠΈΠΌΡΡ
ΠΌΠ΅ΡΠ°Π»Π»ΠΎΠΏΡΠΎΡΠ΅ΠΈΠ½Π°Π· 2-Π³ΠΎ ΠΈ 9-Π³ΠΎ ΡΠΈΠΏΠ°, ΠΊΠΎΡΠΎΡΡΠ΅, ΠΊΠ°ΠΊ ΠΈΠ·Π²Π΅ΡΡΠ½ΠΎ, ΠΈΠ³ΡΠ°ΡΡ ΠΊΠ»ΡΡΠ΅Π²ΡΡ ΡΠΎΠ»Ρ Π² ΠΏΠ°ΡΠΎΠ³Π΅Π½Π΅Π·Π΅ ΡΠ°Π½Π½Π΅Π³ΠΎ ΠΏΠΎΡΡΠΈΠ½ΡΠ°ΡΠΊΡΠ½ΠΎΠ³ΠΎ ΡΠ΅ΠΌΠΎΠ΄Π΅Π»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π°. ΠΡΠΈ ΠΈΠ·ΡΡΠ΅Π½ΠΈΠΈ Π²Π»ΠΈΡΠ½ΠΈΡ Π²Π½ΠΎΠ²Ρ ΡΠΈΠ½ΡΠ΅Π·ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ
ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠΉ Π½Π° ΡΡΠΎΠ²Π΅Π½Ρ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ ΠΌΠ΅ΡΠ°Π»Π»ΠΎΠΏΡΠΎΡΠ΅ΠΈΠ½Π°Π·Ρ-9 Π² ΠΊΡΠΎΠ²ΠΈ ΠΊΡΡΡ Ρ ΠΎΡΡΡΡΠΌ ΠΈΠ½ΡΠ°ΡΠΊΡΠΎΠΌ ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π° Π±ΡΠ»ΠΎ ΠΎΡΠΎΠ±ΡΠ°Π½ΠΎ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠ΅-Π»ΠΈΠ΄Π΅Ρ - 1-({4-[(4-Ρ
Π»ΠΎΡΠ±Π΅Π½Π·ΠΎΠΈΠ») Π°ΠΌΠΈΠ½ΠΎ]ΡΠ΅Π½ΠΈΠ»}ΡΡΠ»ΡΡΠΎΠ½ΠΈΠ»-1_-ΠΏΡΠΎΠ»ΠΈΠ½, - ΠΊΠΎΡΠΎΡΠΎΠ΅ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎ Π±Π»ΠΎΠΊΠΈΡΡΠ΅Ρ ΠΏΠΎΠ²ΡΡΠ΅Π½ΠΈΡ ΡΡΠΎΠ²Π½Ρ ΡΡΠΎΠ³ΠΎ ΡΠ΅ΡΠΌΠ΅Π½ΡΠ° Π² ΠΊΡΠΎΠ²ΠΈ. ΠΡΠΈ ΠΏΠΎΠΌΠΎΡΠΈ ΡΡ
ΠΎΠΊΠ°ΡΠ΄ΠΈΠΎΠ³ΡΠ°ΡΠΈΠΈ ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ ΠΎΡΠΎΠ±ΡΠ°Π½Π½ΠΎΠ΅ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠ΅-Π»ΠΈΠ΄Π΅Ρ ΠΏΠΎ ΡΠ²ΠΎΠ΅ΠΉ ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΠΈ ΠΏΡΠ΅ΠΏΡΡΡΡΠ²ΠΎΠ²Π°ΡΡ ΡΠ°Π·Π²ΠΈΡΠΈΡ ΡΠ΅ΠΌΠΎΠ΄Π΅Π»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π° Π² ΠΎΡΡΡΠ΅ΠΉΡΡΡ ΡΠ°Π·Ρ ΡΠΊΡΠΏΠ΅ΡΠΈΠΌΠ΅Π½ΡΠ°Π»ΡΠ½ΠΎΠ³ΠΎ ΠΈΠ½ΡΠ°ΡΠΊΡΠ° ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π°, ΠΊΠ°ΠΊ ΠΌΠΈΠ½ΠΈΠΌΡΠΌ, Π½Π΅ ΡΡΡΡΠΏΠ°Π΅Ρ ΡΡΠ°Π»ΠΎΠ½Π½ΠΎΠΌΡ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΡ ΠΌΠ΅ΡΠ°Π»Π»ΠΎΠΏΡΠΎΡΠ΅ΠΈΠ½Π°Π· - Π΄ΠΎΠΊΡΠΈΡΠΈΠΊΠ»ΠΈΠ½Ρ
ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΠΊΠ°ΡΠ΄ΠΈΠΎΡΡΠΎΠΏΠ½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΎΡΡΠΎ-Π°Π»ΠΊΠΎΠΊΡΠΈ Π°Π½Π°Π»ΠΎΠ³ΠΎΠ² ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ ΠΠΠ-802
New ortho-alkoxy analogs of the compound ALM-802 1a (N1-(2-methoxybenzyl)-N2-[2-((2-methoxybenzyl)amino)ethyl]ethane-1,2-diamine trihydrochloride) and 1b (N1-(2-ethoxybenzyl)-N2-[2-((2-ethoxybenzyl)amino)ethyl]ethane-1,2-diamine trihydrochloride), which differ from it by the presence of alkoxy groups in the phenyl rings only in the ortho positions. It was established that these structural changes lead to the disappearance of anti-ischemic activity. At the same time, antiarrhythmic activity was revealed in compound 1b on the models of aconitine and calcium chloride arrhythmias in rats (1 mg / kg, intravenously), which was absent in 1a.Π‘ΠΈΠ½ΡΠ΅Π·ΠΈΡΠΎΠ²Π°Π½Ρ Π½ΠΎΠ²ΡΠ΅ ΠΎΡΡΠΎ-Π°Π»ΠΊΠΎΠΊΡΠΈ Π°Π½Π°Π»ΠΎΠ³ΠΈ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ ΠΠΠ-802 β 1a (N1-(2-ΠΌΠ΅ΡΠΎΠΊΡΠΈΠ±Π΅Π½Π·ΠΈΠ»)-N2-[2-((2-ΠΌΠ΅ΡΠΎΠΊΡΠΈΠ±Π΅Π½Π·ΠΈΠ»)Π°ΠΌΠΈΠ½ΠΎ)ΡΡΠΈΠ»] ΡΡΠ°Π½-1,2-Π΄ΠΈΠ°ΠΌΠΈΠ½ ΡΡΠΈΠ³ΠΈΠ΄ΡΠΎΡ
Π»ΠΎΡΠΈΠ΄) ΠΈ 1b (N1-(2-ΡΡΠΎΠΊΡΠΈΠ±Π΅Π½Π·ΠΈΠ»)-N2-[2-((2-ΡΡΠΎΠΊΡΠΈΠ±Π΅Π½Π·ΠΈΠ»)Π°ΠΌΠΈΠ½ΠΎ)ΡΡΠΈΠ»]ΡΡΠ°Π½-1,2-Π΄ΠΈΠ°ΠΌΠΈΠ½ ΡΡΠΈΠ³ΠΈΠ΄ΡΠΎΡ
Π»ΠΎΡΠΈΠ΄), ΠΎΡΠ»ΠΈΡΠ°ΡΡΠΈΠ΅ΡΡ ΠΎΡ Π½Π΅Π³ΠΎ Π½Π°Π»ΠΈΡΠΈΠ΅ΠΌ Π°Π»ΠΊΠΎΠΊΡΠΈ-Π³ΡΡΠΏΠΏ Π² ΡΠ΅Π½ΠΈΠ»ΡΠ½ΡΡ
ΠΊΠΎΠ»ΡΡΠ°Ρ
ΡΠΎΠ»ΡΠΊΠΎ Π² ΠΎΡΡΠΎ-ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ΠΈΡΡ
. Π£ΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΡΠΎ ΡΡΠΈ ΡΡΡΡΠΊΡΡΡΠ½ΡΠ΅ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡ ΠΏΡΠΈΠ²ΠΎΠ΄ΡΡ ΠΊ ΠΈΡΡΠ΅Π·Π½ΠΎΠ²Π΅Π½ΠΈΡ Π°Π½ΡΠΈΠΈΡΠ΅ΠΌΠΈΡΠ΅ΡΠΊΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ. Π ΡΠΎ ΠΆΠ΅ Π²ΡΠ΅ΠΌΡ Ρ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ 1b Π²ΡΡΠ²Π»Π΅Π½Π° Π°Π½ΡΠΈΠ°ΡΠΈΡΠΌΠΈΡΠ΅ΡΠΊΠ°Ρ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Π½Π° ΠΌΠΎΠ΄Π΅Π»ΡΡ
Π°ΠΊΠΎΠ½ΠΈΡΠΈΠ½ΠΎΠ²ΠΎΠΉ ΠΈ Ρ
Π»ΠΎΡΠΈΠ΄ΠΊΠ°Π»ΡΡΠΈΠ΅Π²ΠΎΠΉ Π°ΡΠΈΡΠΌΠΈΠΈ Ρ ΠΊΡΡΡ (1 ΠΌΠ³/ΠΊΠ³, Π²Π½ΡΡΡΠΈΠ²Π΅Π½Π½ΠΎ), ΠΊΠΎΡΠΎΡΠ°Ρ ΠΎΡΡΡΡΡΡΠ²ΠΎΠ²Π°Π»Π° Ρ 1a
ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ Π²Π»ΠΈΡΠ½ΠΈΡ ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ΠΈΡ ΠΌΠ΅ΡΠΎΠΊΡΠΈ-Π³ΡΡΠΏΠΏΡ Π½Π° ΠΊΠ°ΡΠ΄ΠΈΠΎΡΡΠΎΠΏΠ½ΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΡ ΠΠΠ-802
A new compound ALM-803 (trihydrochloride N1-(3,4,5-trimethoxybenzyl)-N2-{2-[(3,4,5-trimethoxybenzyl)amino]ethyl}-1,2-ethanediamine) was synthesized as analog of ALM 802, differing from it by the position of the methoxy groups in the phenyl rings. It is established that this structural change leads to the disappearance of anti-ischemic activity and antiarrhythmic activity on the model of aconitine arrhythmia in rats, but the antiarrhythmic activity on models of chloride-calcium arrhythmia and electrical fibrillation of the heart of rats remained (1 mg/kg, intravenously).Π‘ΠΈΠ½ΡΠ΅Π·ΠΈΡΠΎΠ²Π°Π½ΠΎ Π½ΠΎΠ²ΠΎΠ΅ ΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠ΅ ΠΠΠ-803 (ΡΡΠΈΠ³ΠΈΠ΄ΡΠΎΡ
Π»ΠΎΡΠΈΠ΄ β-(3,4,5-ΡΡΠΈΠΌΠ΅ΡΠΎΠΊΡΠΈΠ±Π΅Π½Π·ΠΈΠ»)-β-{2-[(3,4,5-ΡΡΠΈΠΌΠ΅ΡΠΎΠΊΡΠΈΠ±Π΅Π½Π·ΠΈΠ») Π°ΠΌΠΈΠ½ΠΎ]-ΡΡΠΈΠ»}-1,2-ΡΡΠ°Π½Π΄ΠΈΠ°ΠΌΠΈΠ½Π°) - Π°Π½Π°Π»ΠΎΠ³ ΠΠΠ-802, ΠΎΡΠ»ΠΈΡΠ°ΡΡΠΈΠΉΡΡ ΠΎΡ Π½Π΅Π³ΠΎ ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ΠΈΠ΅ΠΌ ΠΌΠ΅ΡΠΎΠΊΡΠΈ-Π³ΡΡΠΏΠΏ Π² ΡΠ΅Π½ΠΈΠ»ΡΠ½ΡΡ
ΠΊΠΎΠ»ΡΡΠ°Ρ
. Π£ΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΎ, ΡΡΠΎ ΡΡΠΎ ΡΡΡΡΠΊΡΡΡΠ½ΠΎΠ΅ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ ΠΈΡΡΠ΅Π·Π½ΠΎΠ²Π΅Π½ΠΈΡ Π°Π½ΡΠΈΠΈΡΠ΅ΠΌΠΈΡΠ΅ΡΠΊΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΈ Π°Π½ΡΠΈΠ°ΡΠΈΡΠΌΠΈΡΠ΅ΡΠΊΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π½Π° ΠΌΠΎΠ΄Π΅Π»ΠΈ Π°ΠΊΠΎΠ½ΠΈΡΠΈΠ½ΠΎΠ²ΠΎΠΉ Π°ΡΠΈΡΠΌΠΈΠΈ Ρ ΠΊΡΡΡ, Π½ΠΎ ΠΏΡΠΈ ΡΡΠΎΠΌ Π°Π½ΡΠΈΠ°ΡΠΈΡΠΌΠΈΡΠ΅ΡΠΊΠ°Ρ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ Π½Π° ΠΌΠΎΠ΄Π΅Π»ΡΡ
Ρ
Π»ΠΎΡΠΈΠ΄ΠΊΠ°Π»ΡΡΠΈΠ΅Π²ΠΎΠΉ Π°ΡΠΈΡΠΌΠΈΠΈ ΠΈ ΡΠ»Π΅ΠΊΡΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠΈΠ±ΡΠΈΠ»Π»ΡΡΠΈΠΈ ΠΆΠ΅Π»ΡΠ΄ΠΎΡΠΊΠΎΠ² ΡΠ΅ΡΠ΄ΡΠ° ΠΊΡΡΡ ΡΠΎΡ
ΡΠ°Π½ΡΠ΅ΡΡΡ (1 ΠΌΠ³/ΠΊΠ³, Π²Π½ΡΡΡΠΈΠ²Π΅Π½Π½ΠΎ)
- β¦