Π ΠΎΠ»Ρ ΠΏΠΎΡΡΡΡΠ°Π½ΡΠ»ΡΡΠΈΠΎΠ½Π½ΡΡ ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΠΉ Π² ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠ΅ΠΉ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ ΠΏΡΠΈ Π³Π΅Π½ΠΎΡΠΎΠΊΡΠΈΡΠ΅ΡΠΊΠΎΠΌ ΡΡΡΠ΅ΡΡΠ΅ Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ Π562
ΠΡΡΠ³ΠΈΠΌ Π²Π°ΠΆΠ½Π΅ΠΉΡΠΈΠΌ ΡΠΏΠΎΡΠΎΠ±ΠΎΠΌ ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠ΅ΠΉ Π±Π΅Π»ΠΊΠΎΠ² ΡΠ²Π»ΡΡΡΡΡ ΡΠ°Π·Π»ΠΈΡΠ½ΡΠ΅ ΠΏΠΎΡΡΡΡΠ°Π½ΡΠ»ΡΡΠΈΠΎΠ½Π½ΡΠ΅ ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΠΈ. ΠΠΎΠ»ΡΡΠΎΠ΅ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²ΠΎ ΠΏΡΠΎΡΠ΅ΠΎΠΌΠ½ΡΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ ΠΏΡΠΈΠ²Π΅Π»ΠΎ ΠΊ Π²ΡΡΠ²Π»Π΅Π½ΠΈΡ ΠΌΠ½ΠΎΠΆΠ΅ΡΡΠ²Π° ΡΠ°ΠΉΡΠΎΠ² ΡΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡ 20S ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ ΠΈ 19S ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΠ½ΡΡ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠΎΠ² (Claverol et al., 2002; Beausoleil et al., 2004; Rush et al., 2005; Wang et al., 2007). ΠΡΠΎΠΌΠ΅ ΡΠΎΠ³ΠΎ, Π±ΡΠ»ΠΈ ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½Ρ ΡΠ°ΠΊΠΈΠ΅… Π§ΠΈΡΠ°ΡΡ Π΅ΡΡ >
- Π‘ΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΠ΅
- ΠΡΠ΄Π΅ΡΠΆΠΊΠ°
- ΠΠΈΡΠ΅ΡΠ°ΡΡΡΠ°
- ΠΡΡΠ³ΠΈΠ΅ ΡΠ°Π±ΠΎΡΡ
- ΠΠΎΠΌΠΎΡΡ Π² Π½Π°ΠΏΠΈΡΠ°Π½ΠΈΠΈ
Π‘ΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΠ΅
- 1. ΠΠ²Π΅Π΄Π΅Π½ΠΈΠ΅
- 1. 1. ΠΠΊΡΡΠ°Π»ΡΠ½ΠΎΡΡΡ ΠΏΡΠΎΠ±Π»Π΅ΠΌΡ
- 1. 2. Π¦Π΅Π»ΠΈ ΠΈ Π·Π°Π΄Π°ΡΠΈ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ
- 1. 3. ΠΡΠ½ΠΎΠ²Π½ΡΠ΅ ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ΠΈΡ, Π²ΡΠ½ΠΎΡΠΈΠΌΡΠ΅ Π½Π° Π·Π°ΡΠΈΡΡ
- 1. 4. ΠΠ°ΡΡΠ½Π°Ρ Π½ΠΎΠ²ΠΈΠ·Π½Π° ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΡΡ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠΎΠ²
- 1. 5. Π’Π΅ΠΎΡΠ΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ΅ ΠΈ ΠΏΡΠ°ΠΊΡΠΈΡΠ΅ΡΠΊΠΎΠ΅ Π·Π½Π°ΡΠ΅Π½ΠΈΠ΅ ΡΠ°Π±ΠΎΡΡ
- 1. 6. ΠΡΠ±Π»ΠΈΠΊΠ°ΡΠΈΠΈ
- 1. 7. ΠΠΏΡΠΎΠ±Π°ΡΠΈΡ ΡΠ°Π±ΠΎΡΡ
- 1. 8. Π€ΠΈΠ½Π°Π½ΡΠΎΠ²Π°Ρ ΠΏΠΎΠ΄Π΄Π΅ΡΠΆΠΊΠ° ΡΠ°Π±ΠΎΡΡ
- 1. 9. Π‘ΡΡΡΠΊΡΡΡΠ° ΠΈ ΠΎΠ±ΡΠ΅ΠΌ ΡΠ°Π±ΠΎΡΡ
- 2. ΠΠ±Π·ΠΎΡ Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΡ
- 2. 1. ΠΡΠΎΡΠ΅Π°ΡΠΎΠΌΠ°
- 2. 2. 26Π ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌΠ°
- 2. 3. 20Π ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌΠ°
- 2. 3. 1. ΠΠ΅ΡΠ΅ΡΠΎΠ³Π΅Π½Π½ΠΎΡΡΡ ΠΏΠΎΠΏΡΠ»ΡΡΠΈΠΈ 20Π ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ
- 2. 4. Π Π΅Π³ΡΠ»ΡΡΠΎΡΠ½ΡΠ΅ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΡ
- 2. 4. 1. 19Π ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΠ½Π°Ρ ΡΠ°ΡΡΠΈΡΠ° (Π Π700)
- 2. 4. 2. 118 ΡΠ΅Π³ΡΠ»ΡΡΠΎΡ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ (Π Π28)
- 2. 4. 3. Π Π΅Π³ΡΠ»ΡΡΠΎΡ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ Π Π200 (Π1Ρ10)
- 2. 4. 4. Π Π΅Π³ΡΠ»ΡΡΠΎΡ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ Π
- 2. 5. ΠΠΎΠΊΠ°Π»ΠΈΠ·Π°ΡΠΈΡ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ Π² ΠΊΠ»Π΅ΡΠΊΠ΅
- 2. 5. 1. ΠΡΠΎΡΠ΅Π°ΡΠΎΠΌΡ Π² ΡΠ΄ΡΠ΅
- 2. 6. ΠΡΠΎΡΠ΅ΠΎΠ»ΠΈΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ
- 2. 7. Π£Π±ΠΈΠΊΠ²ΠΈΡΠΈΠ½-Π·Π°Π²ΠΈΡΠΈΠΌΡΠΉ ΠΏΡΠΎΡΠ΅ΠΎΠ»ΠΈΠ·
- 2. 8. Π£Π±ΠΈΠΊΠ²ΠΈΡΠΈΠ½-Π½Π΅Π·Π°Π²ΠΈΡΠΈΠΌΡΠΉ ΠΏΡΠΎΡΠ΅ΠΎΠ»ΠΈΠ·
- 2. 9. ΠΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΡ ΠΏΡΠΎΡΠ΅ΠΎΠ»ΠΈΡΠΈΡΠ΅ΡΠΊΠΈΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠ΅ΠΉ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ
- 2. 10. ΠΠ½Π΄ΠΎΡΠΈΠ±ΠΎΠ½ΡΠΊΠ»Π΅Π°Π·Π½Π°Ρ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ
- 2. 11. ΠΠΎΡΡΡΡΠ°Π½ΡΠ»ΡΡΠΈΠΎΠ½Π½ΡΠ΅ ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΠΈ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ
- 2. 11. 1. Π€ΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅
- 2. 11. 2. ΠΡΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅
- 2. 11. 3. Π-Π³Π»ΠΈΠΊΠΎΠ·ΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅
- 2. 11. 4. ΠΠΊΠΈΡΠ»Π΅Π½ΠΈΠ΅ ΡΠ΅ΡΠΎΡΠΎΠ΄Π΅ΡΠΆΠ°ΡΠΈΡ Π°ΠΌΠΈΠ½ΠΎΠΊΠΈΡΠ»ΠΎΡ
- 2. 11. 5. ΠΠΎΠ½ΠΎΡΠ±ΠΈΠΊΠ²ΠΈΡΠΈΠ½ΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅
- 2. 11. 6. ΠΡΡΠ³ΠΈΠ΅ ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΠΈ ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ
- 2. 12. ΠΠ»ΠΈΡΠ½ΠΈΠ΅ ΡΠΈΠ·ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΠΎΡΡΠΎΡΠ½ΠΈΡ ΠΊΠ»Π΅ΡΠΊΠΈ Π½Π° ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡΠ½ΡΠΉ ΡΠΎΡΡΠ°Π² ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ
- 3. ΠΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ ΠΈ ΠΌΠ΅ΡΠΎΠ΄Ρ
- 3. 1. ΠΡΠ»ΡΡΠΈΠ²ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΠΊΠ»Π΅ΡΠΎΠΊ Π
- 3. 2. ΠΡΠ΄Π΅Π»Π΅Π½ΠΈΠ΅ ΡΠΈΡΠΎΠΏΠ»Π°Π·ΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΡ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ
- 3. 3. ΠΡΠ΄Π΅Π»Π΅Π½ΠΈΠ΅ ΡΠ΄Π΅ΡΠ½ΡΡ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ
- 3. 4. ΠΠ²ΡΠΌΠ΅ΡΠ½ΡΠΉ ΡΠ»Π΅ΠΊΡΡΠΎΡΠΎΡΠ΅Π· Π±Π΅Π»ΠΊΠΎΠ²
- 3. 4. 1. ΠΠ·ΠΎΡΠ»Π΅ΠΊΡΡΠΈΡΠ΅ΡΠΊΠΎΠ΅ ΡΠΎΠΊΡΡΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ (ΠΠΠ€)
- 3. 4. 2. ΠΠ»Π΅ΠΊΡΡΠΎΡΠΎΡΠ΅ΡΠΈΡΠ΅ΡΠΊΠΎΠ΅ ΡΠ°Π·Π΄Π΅Π»Π΅Π½ΠΈΠ΅ Π±Π΅Π»ΠΊΠΎΠ² ΠΏΠΎ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΡΠΌ ΠΌΠ°ΡΡΠ°ΠΌ Π² Π΄Π΅Π½Π°ΡΡΡΠΈΡΡΡΡΠΈΡ ΡΡΠ»ΠΎΠ²ΠΈΡΡ
- 3. 5. ΠΠ΅ΡΡΠ΅ΡΠ½-Π±Π»ΠΎΡΡΠΈΠ½Π³
- 3. 5. 1. ΠΠ΅ΡΠ΅Π½ΠΎΡ Π±Π΅Π»ΠΊΠΎΠ² ΠΈΠ· Π³Π΅Π»Ρ Π½Π° ΠΌΠ΅ΠΌΠ±ΡΠ°Π½Ρ PVDF
- 3. 5. 2. ΠΠΌΠΌΡΠ½ΠΎΠ±Π»ΠΎΡΡΠΈΠ½Π³ Ρ Π°Π½ΡΠΈΡΠ΅Π»Π°ΠΌΠΈ ΠΊ ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡΠ°ΠΌ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ
- 3. 5. 3. ΠΡΠΌΡΠ²ΠΊΠ° ΠΌΠ΅ΠΌΠ±ΡΠ°Π½ ΠΎΡ Π°Π½ΡΠΈΡΠ΅Π» Π΄Π»Ρ ΠΏΠΎΠ²ΡΠΎΡΠ½ΠΎΠ³ΠΎ ΠΎΠΊΡΠ°ΡΠΈΠ²Π°Π½ΠΈΡ
- 3. 6. ΠΠ°ΡΡ-ΡΠΏΠ΅ΠΊΡΡΠΎΠΌΠ΅ΡΡΠΈΡΠ΅ΡΠΊΠΈΠΉ Π°Π½Π°Π»ΠΈΠ· Π±Π΅Π»ΠΊΠΎΠ²
- 3. 7. Π£Π±ΠΈΠΊΠ²ΠΈΡΠΈΠ½ΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π±Π΅Π»ΠΊΠΎΠ² in vitro
- 3. 8. ΠΠ·ΠΌΠ΅ΡΠ΅Π½ΠΈΠ΅ ΠΏΠ΅ΠΏΡΠΈΠ΄Π°Π·Π½ΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠ΅ΠΉ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ
- 3. 9. ΠΡΠΈΠ³ΠΎΡΠΎΠ²Π»Π΅Π½ΠΈΠ΅ ΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ ΡΠΊΡΡΡΠ°ΠΊΡΠ°
- 4. Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ
- 4. 1. ΠΠ½Π΄ΡΠΊΡΠΈΡ ΠΏΠΎΠ²ΡΠ΅ΠΆΠ΄Π΅Π½ΠΈΡ ΠΠΠ Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ Π562 Π΄ΠΎΠΊΡΠΎΡΡΠ±ΠΈΡΠΈΠ½ΠΎΠΌ ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ ΠΏΠΎΠ²ΡΡΠ΅Π½ΠΈΡ Ρ ΠΈΠΌΠΎΡΡΠΈΠΏΡΠΈΠ½ΠΎΠΏΠΎΠ΄ΠΎΠ±Π½ΠΎΠΉ ΠΈ ΠΊΠ°ΡΠΏΠ°Π·ΠΎΠΏΠΎΠ΄ΠΎΠ±Π½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠ΅ΠΉ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ
- 4. 2. ΠΠ½Π΄ΡΠΊΡΠΈΡ ΠΏΠΎΠ²ΡΠ΅ΠΆΠ΄Π΅Π½ΠΈΡ ΠΠΠ Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ Π562 Π΄ΠΎΠΊΡΠΎΡΡΠ±ΠΈΡΠΈΠ½ΠΎΠΌ ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡ ΡΠΏΠ΅ΠΊΡΡΠ° ΠΏΠΎΡΡΡΡΠ°Π½ΡΠ»ΡΡΠΈΠΎΠ½Π½ΡΡ ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΠΉ ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ
- 4. 3. Π ΠΊΠ»Π΅ΡΠΊΠ°Ρ Π562 ΠΏΡΠΈΡΡΡΡΡΠ²ΡΡΡ ΡΡΡΠΆΠ΅Π»ΡΠ½Π½ΡΠ΅ ΠΈΠ·ΠΎΡΠΎΡΠΌΡ ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡ Π°5, Π°Π± ΠΈ Π°
- 4. 4. Π£Π±ΠΈΠΊΠ²ΠΈΡΠΈΠ½ΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ in vitro ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ ΠΏΠΎΠ΄Π°Π²Π»Π΅Π½ΠΈΡ ΠΈΡ ΠΏΠ΅ΠΏΡΠΈΠ΄Π°Π·Π½ΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠ΅ΠΉ
- 5. ΠΠ±ΡΡΠ·Π²Π΄Π΅Π½ΠΈΠ΅
- 5. 1. ΠΠΊΡΠΈΠ²Π°ΡΠΈΡ ΠΏΠ΅ΠΏΡΠΈΠ΄Π°Π·Π½ΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠ΅ΠΉ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ ΠΏΡΠΈ ΠΈΠ½Π΄ΡΠΊΡΠΈΠΈ ΠΏΠΎΠ²ΡΠ΅ΠΆΠ΄Π΅Π½ΠΈΠΉ ΠΠΠ Π΄ΠΎΠΊΡΠΎΡΡΠ±ΠΈΡΠΈΠ½ΠΎΠΌ
- 5. 2. ΠΠΎΡΡΡΡΠ°Π½ΡΠ»ΡΡΠΈΠΎΠ½Π½ΡΠ΅ ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΠΈ ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ ΠΏΡΠΈ ΠΈΠ½Π΄ΡΠΊΡΠΈΠΈ ΠΏΠΎΠ²ΡΠ΅ΠΆΠ΄Π΅Π½ΠΈΠΉ ΠΠΠ Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ
Π562 Π΄ΠΎΠΊΡΠΎΡΡΠ±ΠΈΡΠΈΠ½ΠΎΠΌ
- 5. 2. 1. Π€ΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅
- 5. 2. 2. Π£Π±ΠΈΠΊΠ²ΠΈΡΠΈΠ½ΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅
- 5. 3. Π‘ΡΠ±ΠΏΠΎΠΏΡΠ»ΡΡΠΈΠΈ ΡΠ΄Π΅ΡΠ½ΡΡ ΠΈ ΡΠΈΡΠΎΠΏΠ»Π°Π·ΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΡ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ ΠΎΡΠ»ΠΈΡΠ°ΡΡΡΡ Π½Π°Π±ΠΎΡΠΎΠΌ ΠΏΠΎΡΡΡΡΠ°Π½ΡΠ»ΡΡΠΈΠΎΠ½Π½ΡΡ ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΠΉ
- 5. 4. Π Π΅Π³ΡΠ»ΡΡΠΈΡ ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΠΈ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ ΠΊ ΡΠ°ΡΡΠ΅ΠΏΠ»Π΅Π½ΠΈΡ Π±Π΅Π»ΠΊΠΎΠ² ΡΠ±ΠΈΠΊΠ²ΠΈΡΠΈΠ½ΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ
- 6. ΠΡΠ²ΠΎΠ΄Ρ
- Π‘ΠΏΠΈΡΠΎΠΊ ΡΠΎΠΊΡΠ°ΡΠ΅Π½ΠΈΠΉ
Π ΠΎΠ»Ρ ΠΏΠΎΡΡΡΡΠ°Π½ΡΠ»ΡΡΠΈΠΎΠ½Π½ΡΡ ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΠΉ Π² ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠ΅ΠΉ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ ΠΏΡΠΈ Π³Π΅Π½ΠΎΡΠΎΠΊΡΠΈΡΠ΅ΡΠΊΠΎΠΌ ΡΡΡΠ΅ΡΡΠ΅ Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ Π562 (ΡΠ΅ΡΠ΅ΡΠ°Ρ, ΠΊΡΡΡΠΎΠ²Π°Ρ, Π΄ΠΈΠΏΠ»ΠΎΠΌ, ΠΊΠΎΠ½ΡΡΠΎΠ»ΡΠ½Π°Ρ)
1.1. ΠΠΊΡΡΠ°Π»ΡΠ½ΠΎΡΡΡ ΠΏΡΠΎΠ±Π»Π΅ΠΌΡ.
Π Π΅Π³ΡΠ»ΡΡΠΎΡΡ ΠΏΡΠΎΡΠ΅ΠΎΠ»ΠΈΡΠΈΡΠ΅ΡΠΊΠΈΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠ΅ΠΉ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ ΠΏΠΎΠ»ΡΡΠΈΠ»ΠΈ ΡΠΈΡΠΎΠΊΠΎΠ΅ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ Π² ΠΌΠ΅Π΄ΠΈΡΠΈΠ½Π΅ Π² ΠΊΠ°ΡΠ΅ΡΡΠ²Π΅ ΠΏΡΠΎΡΠΈΠ²ΠΎΠΎΠΏΡΡ ΠΎΠ»Π΅Π²ΡΡ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠ². ΠΠ»Ρ Π»Π΅ΡΠ΅Π½ΠΈΡ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΡΡΡΡ ΡΠ°Π·Π»ΠΈΡΠ½ΡΠ΅ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΡΡ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ: Π±ΠΎΡΡΠ΅Π·ΠΎΠΌΠΈΠ±, ΡΠΏΠΎΠΊΡΠΈΠΌΠΈΡΠΈΠ½, Π»Π°ΠΊΡΠ°ΡΠΈΡΡΠΈΠ½, ΡΠ°Π»ΠΈΠ½ΠΎΡΠΏΠΎΡΠ°ΠΌΠΈΠ΄Ρ, ΡΠΈΡΠΈΠ½Π³ΠΎΠ»ΠΈΠ½ ΠΈ Π΄ΡΡΠ³ΠΈΠ΅ (Moore et al., 2008). ΠΠ°Π½Π½ΡΠ΅ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΡ ΡΠΏΠΎΡΠΎΠ±Π½Ρ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΈ ΠΏΠΎΠ΄Π°Π²Π»ΡΡΡ ΠΎΠ΄Π½Ρ ΠΈΠ»ΠΈ Π½Π΅ΡΠΊΠΎΠ»ΡΠΊΠΎ ΠΏΠ΅ΠΏΡΠΈΠ΄Π°Π·Π½ΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠ΅ΠΉ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ, ΠΈΠ·ΠΌΠ΅Π½ΡΡ ΡΠΏΠ΅ΠΊΡΡ ΡΠ°ΡΡΠ΅ΠΏΠ»ΡΠ΅ΠΌΡΡ ΠΈΠΌΠΈ Π±Π΅Π»ΠΊΠΎΠ²ΡΡ ΡΡΠ±ΡΡΡΠ°ΡΠΎΠ². ΠΠ΄Π½Π°ΠΊΠΎ Π² ΠΏΡΠΈΡΠΎΠ΄Π΅ ΠΏΡΠΎΡΠ΅ΠΎΠ»ΠΈΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ ΡΠ°ΠΊΠΆΠ΅ ΠΏΠΎΠ΄Π²Π΅ΡΠ³Π°ΡΡΡΡ ΡΠΎΠ½ΠΊΠΎΠΌΡ ΡΠ΅Π³ΡΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΏΡΠΈ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡΡ ΡΠΈΠ·ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΠΎΡΡΠΎΡΠ½ΠΈΡ ΠΊΠ»Π΅ΡΠΊΠΈ ΠΈΠ»ΠΈ ΡΡΡΠ΅ΡΡΠΎΠ²ΡΡ Π²ΠΎΠ·Π΄Π΅ΠΉΡΡΠ²ΠΈΡΡ . Π ΡΡΠΈΡ ΡΠ»ΡΡΠ°ΡΡ ΠΈΠ·ΠΌΠ΅Π½ΡΠ΅ΡΡΡ ΠΊΠ°ΠΊ ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡΠ½ΡΠΉ ΡΠΎΡΡΠ°Π² ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ, ΡΠ°ΠΊ ΠΈ ΡΠΏΠ΅ΠΊΡΡ ΠΈΡ ΠΏΠΎΡΡΡΡΠ°Π½ΡΠ»ΡΡΠΈΠΎΠ½Π½ΡΡ ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΠΉ.
ΠΠ°ΠΈΠ±ΠΎΠ»Π΅Π΅ ΠΈΠ·Π²Π΅ΡΡΠ½ΡΠΌ ΠΏΡΠΈΠΌΠ΅ΡΠΎΠΌ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌΡ Ρ ΠΈΠ·ΠΌΠ΅Π½ΡΠ½Π½ΡΠΌ ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡΠ½ΡΠΌ ΡΠΎΡΡΠ°Π²ΠΎΠΌ ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΈΠΌΠΌΡΠ½ΠΎΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌΠ°, Π² ΠΊΠΎΡΠΎΡΠΎΠΉ ΠΊΠ°ΡΠ°Π»ΠΈΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡΡ? l, ?2 ΠΈ ?5 Π·Π°ΠΌΠ΅Π½Π΅Π½Ρ ΠΈΡ ΠΈΠ½Π΄ΡΡΠΈΠ±Π΅Π»ΡΠ½ΡΠΌΠΈ Π°Π½Π°Π»ΠΎΠ³Π°ΠΌΠΈ? li, ?2i ΠΈ ?5i, ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²Π΅Π½Π½ΠΎ. Π‘ΠΎΠ΄Π΅ΡΠΆΠ°Π½ΠΈΠ΅ Π² ΠΊΠ»Π΅ΡΠΊΠ΅ ΡΠ°ΠΊΠΈΡ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ ΡΠ²Π΅Π»ΠΈΡΠΈΠ²Π°Π΅ΡΡΡ ΠΏΠΎΠ΄ Π²ΠΎΠ·Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ Π³Π°ΠΌΠΌΠ°-ΠΈΠ½ΡΠ΅ΡΡΠ΅ΡΠΎΠ½Π°. ΠΠ΅ΠΏΡΠΈΠ΄Π°Π·Π½ΡΠ΅ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΈΠΌΠΌΡΠ½ΠΎΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌΡ ΡΡΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎ ΠΎΡΠ»ΠΈΡΠ°ΡΡΡΡ ΠΎΡ ΡΠ°ΠΊΠΎΠ²ΡΡ Π΄Π»Ρ ΠΎΠ±ΡΡΠ½ΠΎΠΉ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌΡ, ΡΡΠΎ ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ Π±ΠΎΠ»Π΅Π΅ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΠΌΡ ΠΎΠ±ΡΠ°Π·ΠΎΠ²Π°Π½ΠΈΡ ΠΏΠ΅ΠΏΡΠΈΠ΄ΠΎΠ² Π΄Π»Ρ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½ΠΈΡ Π½Π° ΠΌΠΎΠ»Π΅ΠΊΡΠ»Π°Ρ Π³Π»Π°Π²Π½ΠΎΠ³ΠΎ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠ° Π³ΠΈΡΡΠΎΡΠΎΠ²ΠΌΠ΅ΡΡΠΈΠΌΠΎΡΡΠΈ ΠΊΠ»Π°ΡΡΠ° 1 (Tanaka and Kasahara, 1998). ΠΡΠΎΠΌΠ΅ ΡΠΎΠ³ΠΎ, Π½Π΅Π΄Π°Π²Π½ΠΎ ΠΏΠΎΡΠ²ΠΈΠ»ΠΈΡΡ Π΄Π°Π½Π½ΡΠ΅ ΠΎ ΡΡΡΠ΅ΡΡΠ²ΠΎΠ²Π°Π½ΠΈΠΈ ΡΠΊΠ°Π½Π΅ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ½ΠΎΠΉ ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡΡ ?5t, ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡΡΡΡΠ΅ΠΉΡΡ ΠΈΡΠΊΠ»ΡΡΠΈΡΠ΅Π»ΡΠ½ΠΎ Π² ΡΠΈΠΌΠΎΡΠΈΡΠ°Ρ . ΠΡΠΈ Π²ΠΊΠ»ΡΡΠ΅Π½ΠΈΠΈ ΡΠ°ΠΊΠΎΠ³ΠΎ Π±Π΅Π»ΠΊΠ° Π²ΠΌΠ΅ΡΡΠΎ ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡΡ ?5 ΡΡΠΈΠΏΡΠΈΠ½ΠΎΠΏΠΎΠ΄ΠΎΠ±Π½Π°Ρ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ ΡΡΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎ ΡΠ½ΠΈΠΆΠ°Π΅ΡΡΡ, ΡΡΠΎ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΠ΅Ρ Π³ΠΎΠ²ΠΎΡΠΈΡΡ ΠΎ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ ΠΏΠ΅ΠΏΡΠΈΠ΄Π°Π·Π½ΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠ΅ΠΉ ΡΠ΅ΡΠ΅Π· ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡΠ½ΠΎΠ³ΠΎ ΡΠΎΡΡΠ°Π²Π° ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ (Murata et al., 2008).
ΠΡΡΠ³ΠΈΠΌ Π²Π°ΠΆΠ½Π΅ΠΉΡΠΈΠΌ ΡΠΏΠΎΡΠΎΠ±ΠΎΠΌ ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠ΅ΠΉ Π±Π΅Π»ΠΊΠΎΠ² ΡΠ²Π»ΡΡΡΡΡ ΡΠ°Π·Π»ΠΈΡΠ½ΡΠ΅ ΠΏΠΎΡΡΡΡΠ°Π½ΡΠ»ΡΡΠΈΠΎΠ½Π½ΡΠ΅ ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΠΈ. ΠΠΎΠ»ΡΡΠΎΠ΅ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²ΠΎ ΠΏΡΠΎΡΠ΅ΠΎΠΌΠ½ΡΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ ΠΏΡΠΈΠ²Π΅Π»ΠΎ ΠΊ Π²ΡΡΠ²Π»Π΅Π½ΠΈΡ ΠΌΠ½ΠΎΠΆΠ΅ΡΡΠ²Π° ΡΠ°ΠΉΡΠΎΠ² ΡΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡ 20S ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ ΠΈ 19S ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΠ½ΡΡ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠΎΠ² (Claverol et al., 2002; Beausoleil et al., 2004; Rush et al., 2005; Wang et al., 2007). ΠΡΠΎΠΌΠ΅ ΡΠΎΠ³ΠΎ, Π±ΡΠ»ΠΈ ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½Ρ ΡΠ°ΠΊΠΈΠ΅ ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΠΈ ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½ΡΠΎΠ² ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ ΠΊΠ°ΠΊ Π°ΡΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡ ΠΏΠΎ Π»ΠΈΠ·ΠΈΠ½Π°ΠΌ (Choudhary et al., 2009) ΠΈ N-ΠΊΠΎΠ½ΡΠ°ΠΌ (Claverol et al., 2002), Π³Π»ΠΈΠΊΠΎΠ·ΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ (Zachara and Hart, 2004), 4-Π³ΠΈΠ΄ΡΠΎΠΊΡΠΈ-2-Π½ΠΎΠ½Π΅Π½ΠΈΠ»-Π°Π»ΠΊΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ (Bulteau et al., 2001), ΠΌΠΈΡΠΈΡΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ (Kimura et al., 2003) ΠΈ ΠΎΠΊΠΈΡΠ»Π΅Π½ΠΈΠ΅ ΡΠ΅ΡΠΎΡΠΎΠ΄Π΅ΡΠΆΠ°ΡΠΈΡ Π°ΠΌΠΈΠ½ΠΎΠΊΠΈΡΠ»ΠΎΡ (Schmidt et al., 2006). Π‘ΠΏΠ΅ΠΊΡΡ ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΠΉ ΠΈΠ·ΠΌΠ΅Π½ΡΠ»ΡΡ ΠΏΡΠΈ Π½Π΅ΠΉΡΠΎΠ΄Π΅Π³Π΅Π½Π΅ΡΠ°ΡΠΈΠ²Π½ΡΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡΡ (Diaz-Hernandez et al., 2003; Gillardon et al., 2007), Π·Π°ΠΊΡΠΏΠΎΡΠΊΠ΅/ΡΠ΅ΠΏΠ΅ΡΡΡΠ·ΠΈΠΈ ΠΊΠΎΡΠΎΠ½Π°ΡΠ½ΡΡ ΡΠΎΡΡΠ΄ΠΎΠ² y ΠΊΡΡΡ (Bulteau et al., 2001), Π²ΠΎΠ·ΡΠ°ΡΡΠ½ΠΎΠΉ Π°ΡΡΠΎΡΠΈΠΈ ΠΌΡΡΡ (Husom et al., 2004) ΠΈ ΡΡΠ°ΡΠ΅Π½ΠΈΠΈ ΡΠ΅ΡΡΠ°ΡΠΊΠΈ Ρ ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ° (Ethen et al., 2007), ΡΡΠΎ ΠΌΠΎΠΆΠ΅Ρ Π³ΠΎΠ²ΠΎΡΠΈΡΡ ΠΎ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ ΡΡΠ½ΠΊΡΠΈΠΉ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ Ρ ΠΏΠΎΠΌΠΎΡΡΡ ΠΏΠΎΡΡΡΡΠ°Π½ΡΠ»ΡΡΠΈΠΎΠ½Π½ΡΡ ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΠΉ. ΠΡΠΎΠΌΠ΅ ΡΠΎΠ³ΠΎ, Π΄Π΅ΡΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ Π°Π ΠΈ Π°7 ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΠ»ΠΎ ΠΊ ΡΠ½ΠΈΠΆΠ΅Π½ΠΈΡ Π΄Π²ΡΡ ΠΏΠ΅ΠΏΡΠΈΠ΄Π°Π·Π½ΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠ΅ΠΉ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ (Mason et al., 1996), Π° ΡΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ 20S ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ ΠΈΠ· ΠΊΠ°ΡΠ΄ΠΈΠΎΠΌΠΈΠΎΡΠΈΡΠΎΠ² Π³ΡΡΠ·ΡΠ½ΠΎΠ² ΠΊΠΈΠ½Π°Π·ΠΎΠΉ Π ΠΠ ΠΈΠ»ΠΈ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠΎΡΡΠ°ΡΠ°Π·Ρ Π Π 2Π ΡΡΠΈΠ»ΠΈΠ²Π°Π»ΠΎ ΠΈΡ ΠΏΡΠΎΡΠ΅ΠΎΠ»ΠΈΡΠΈΡΠ΅ΡΠΊΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ, ΠΏΡΠΈΡΡΠΌ ΠΌΠΈΡΠ΅Π½ΡΠΌΠΈ Π΄Π°Π½Π½ΡΡ ΡΠ΅ΡΠΌΠ΅Π½ΡΠΎΠ² ΠΎΠΊΠ°Π·ΡΠ²Π°Π»ΠΈΡΡ ΠΊΠ°ΠΊ Π°-, ΡΠ°ΠΊ ΠΈ Π -ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡΡ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ (Zong et al., 2006; Lu et al., 2008), ΡΡΠΎ ΡΠΎΠΆΠ΅ ΡΠ²ΠΈΠ΄Π΅ΡΠ΅Π»ΡΡΡΠ²ΡΠ΅Ρ Π² ΠΏΠΎΠ»ΡΠ·Ρ Π³ΠΈΠΏΠΎΡΠ΅Π·Ρ ΠΎΠ± ΡΡΠ°ΡΡΠΈΠΈ ΡΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π² ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ ΠΊΠ°ΡΠ°Π»ΠΈΡΠΈΡΠ΅ΡΠΊΠΈΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠ΅ΠΉ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ. ΠΠ»ΠΈΡΠ½ΠΈΠ΅ Π°ΡΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ Π½Π° ΠΈΡ ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΡ ΠΊ ΡΠ°ΡΡΠ΅ΠΏΠ»Π΅Π½ΠΈΡ Π±Π΅Π»ΠΊΠΎΠ² Π±ΡΠ»ΠΎ ΠΊΠΎΡΠ²Π΅Π½Π½ΠΎ ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΎ ΠΏΡΠΈ ΠΈΠ·ΡΡΠ΅Π½ΠΈΠΈ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ ΠΈΠ· ΡΡΠ°ΠΌΠΌΠ° Π΄ΡΠΎΠΆΠΆΠ΅ΠΉ, Π΄Π΅Π»Π΅ΡΠΈΠΎΠ½Π½ΠΎΠ³ΠΎ ΠΏΠΎ Π³Π΅Π½Ρ ΠΎΠ΄Π½ΠΎΠΉ ΠΈΠ· N-Π°ΡΠ΅ΡΠΈΠ»ΡΡΠ°Π½ΡΡΠ΅ΡΠ°Π·. Π’Π°ΠΊΠΈΠ΅ ΠΏΡΠΎΡΠ΅ΠΎΠ»ΠΈΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΡ ΠΎΠ±Π»Π°Π΄Π°Π»ΠΈ ΠΏΠΎΠ½ΠΈΠΆΠ΅Π½Π½ΠΎΠΉ Ρ ΠΈΠΌΠΎΡΡΠΈΠΏΡΠΈΠ½ΠΎΠΏΠΎΠ΄ΠΎΠ±Π½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡΡ, ΡΡΠΎ ΠΌΠΎΠΆΠ΅Ρ Π³ΠΎΠ²ΠΎΡΠΈΡΡ ΠΎ Π½Π΅ΠΎΠ±Ρ ΠΎΠ΄ΠΈΠΌΠΎΡΡΠΈ Π°ΡΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡ Π΄Π»Ρ ΠΏΡΠ°Π²ΠΈΠ»ΡΠ½ΠΎΠ³ΠΎ ΡΡΠ½ΠΊΡΠΈΠΎΠ½ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ (Kimura et al.,.
2000). ΠΠ΄Π½Π°ΠΊΠΎ N-Π°ΡΠ΅ΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π½Π΅ Π²Π»ΠΈΡΠ»ΠΎ Π½Π° ΠΏΡΠΎΡΠ΅ΠΎΠ»ΠΈΡΠΈΡΠ΅ΡΠΊΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΡ 26 S ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ Π΄ΡΠΎΠΆΠΆΠ΅ΠΉ Π² ΠΏΡΠΈΡΡΡΡΡΠ²ΠΈΠΈ ΠΠ’Π€ (Kimura et al., 2003), ΡΡΠΎ ΠΏΠΎΠ·Π²ΠΎΠ»ΠΈΠ»ΠΎ ΠΏΡΠ΅Π΄ΠΏΠΎΠ»ΠΎΠΆΠΈΡΡ Π²Π»ΠΈΡΠ½ΠΈΠ΅ Π΄Π°Π½Π½ΠΎΠΉ ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΠΈ Π½Π° ΠΏΡΠΈΡΠΎΠ΅Π΄ΠΈΠ½Π΅Π½ΠΈΠ΅ ΡΠ΅Π³ΡΠ»ΡΡΠΎΡΠ½ΡΡ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠΎΠ² ΠΊ 20S ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌΠ΅.
ΠΡΠΎΠΌΠ΅ ΠΏΠ΅ΡΠ΅ΡΠΈΡΠ»Π΅Π½Π½ΡΡ Π²ΡΡΠ΅ ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΠΉ, ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡΡ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ ΡΠ°ΠΊΠΆΠ΅ ΠΌΠΎΠ³ΡΡ ΠΏΠΎΠ΄Π²Π΅ΡΠ³Π°ΡΡΡΡ ΡΠ±ΠΈΠΊΠ²ΠΈΡΠΈΠ½ΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ. Π‘ΡΡΠ΅ΡΡΠ²ΡΠ΅Ρ ΡΠΎΠ»ΡΠΊΠΎ Π΄Π²Π΅ ΠΏΡΠ±Π»ΠΈΠΊΠ°ΡΠΈΠΈ ΠΎ Π½Π°Π»ΠΈΡΠΈΠΈ Π½Π° ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌΠ½ΡΡ ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡΠ°Ρ ΡΠ°ΠΉΡΠΎΠ² ΡΠ±ΠΈΠΊΠ²ΠΈΡΠΈΠ½ΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ (Denis et al., 2007; Meierhofer et al., 2008). ΠΠ°Π½Π½ΡΠ΅ ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΠΈ Π±ΡΠ»ΠΈ ΠΎΠ±Π½Π°ΡΡΠΆΠ΅Π½Ρ Π² ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ΅ ΡΠΊΡΠΈΠ½ΠΈΠ½Π³Π° ΡΠΈΡΠΎΠΊΠΎΠ³ΠΎ ΡΠΏΠ΅ΠΊΡΡΠ° ΡΠ±ΠΈΠΊΠ²ΠΈΡΠΈΠ½ΠΈΠ»ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ Π±Π΅Π»ΠΊΠΎΠ², ΠΈ ΠΈΡ ΡΡΠ½ΠΊΡΠΈΠΈ ΡΠΎΠ²Π΅ΡΡΠ΅Π½Π½ΠΎ Π½Π΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½Ρ. ΠΠ΅ΠΆΠ΄Ρ ΡΠ΅ΠΌ, ΡΠ±ΠΈΠΊΠ²ΠΈΡΠΈΠ½ΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠΏΠΎΡΠΎΠ±Π½ΠΎ Π½Π΅ ΡΠΎΠ»ΡΠΊΠΎ Π½Π°ΠΏΡΠ°Π²Π»ΡΡΡ Π±Π΅Π»ΠΊΠΈ Π½Π° ΡΠ°ΡΡΠ΅ΠΏΠ»Π΅Π½ΠΈΠ΅ ΠΏΠΎ ΡΠ±ΠΈΠΊΠ²ΠΈΡΠΈΠ½-Π·Π°Π²ΠΈΡΠΈΠΌΠΎΠΌΡ ΠΌΠ΅Ρ Π°Π½ΠΈΠ·ΠΌΡ (Glickman and Ciechanover, 2002), Π½ΠΎ ΠΈ ΡΠ΅Π³ΡΠ»ΠΈΡΠΎΠ²Π°ΡΡ ΠΊΠ°ΡΠ°Π»ΠΈΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ Π½Π΅ΠΊΠΎΡΠΎΡΡΡ Π±Π΅Π»ΠΊΠΎΠ² (Bienko et al., 2010), Π° ΡΠ°ΠΊΠΆΠ΅ ΠΈΡ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΡΡ Π»ΠΎΠΊΠ°Π»ΠΈΠ·Π°ΡΠΈΡ (Chen and Mallampalli, 2009) ΠΈ Π±Π΅Π»ΠΎΠΊ-Π±Π΅Π»ΠΊΠΎΠ²ΡΠ΅ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΡ (Mosesson and Yarden, 2006). ΠΠΎΠ½ΠΎΡΠ±ΠΈΠΊΠ²ΠΈΡΠΈΠ½ΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΠΈΠ³ΡΠ°Π΅Ρ ΠΊΠ»ΡΡΠ΅Π²ΡΡ ΡΠΎΠ»Ρ Π² ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ ΡΠ°ΠΊΠΈΡ ΠΏΡΠΎΡΠ΅ΡΡΠΎΠ² ΠΊΠ°ΠΊ ΡΠ½Π΄ΠΎΡΠΈΡΠΎΠ·, ΡΠ΅ΠΏΠ°ΡΠ°ΡΠΈΡ, ΠΏΠ΅ΡΠ΅Π΄Π°ΡΠ° ΡΠΈΠ³Π½Π°Π»Π° ΠΈ Π΄ΡΡΠ³ΠΈΠ΅. ΠΠ΅ ΠΈΡΠΊΠ»ΡΡΠ΅Π½ΠΎ, ΡΡΠΎ ΠΏΠΎΠ΄ΠΎΠ±Π½ΡΠ΅ ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΠΈ ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ ΠΌΠΎΠ³ΡΡ ΠΈΠΌΠ΅ΡΡ Π²Π°ΠΆΠ½ΠΎΠ΅ ΡΠΈΠ·ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΎΠ΅ Π·Π½Π°ΡΠ΅Π½ΠΈΠ΅ Π΄Π»Ρ ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠ³ΠΎ ΠΏΡΠΎΡΠ΅ΠΎΠ»ΠΈΠ·Π°, ΠΏΠΎΡΡΠΎΠΌΡ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»ΡΠ΅ΡΡΡ Π½Π΅ΠΎΠ±Ρ ΠΎΠ΄ΠΈΠΌΡΠΌ ΡΡΠ°ΡΠ΅Π»ΡΠ½ΠΎΠ΅ ΠΈΠ·ΡΡΠ΅Π½ΠΈΠ΅ ΡΠΎΠ»ΠΈ ΡΠ±ΠΈΠΊΠ²ΠΈΡΠΈΠ½ΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ Π² ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ ΠΈΡ ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΠΈ ΠΊ ΡΠ°ΡΡΠ΅ΠΏΠ»Π΅Π½ΠΈΡ Π±Π΅Π»ΠΊΠΎΠ²ΡΡ ΡΡΠ±ΡΡΡΠ°ΡΠΎΠ² ΠΈ Π΄ΡΡΠ³ΠΈΡ ΡΡΠ½ΠΊΡΠΈΠΉ Π² ΠΊΠ»Π΅ΡΠΊΠ΅.
ΠΠΠ-ΠΏΠΎΠ²ΡΠ΅ΠΆΠ΄Π°ΡΡΠΈΠΉ Π°Π³Π΅Π½Ρ Π΄ΠΎΠΊΡΠΎΡΡΠ±ΠΈΡΠΈΠ½ ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΏΡΠΎΡΠΈΠ²ΠΎΡΠ°ΠΊΠΎΠ²ΡΠΌ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠΎΠΌ Π°Π½ΡΡΠ°ΡΠΈΠΊΠ»ΠΈΠ½ΠΎΠ²ΠΎΠΉ Π³ΡΡΠΏΠΏΡ, ΡΠΈΡΠΎΠΊΠΎ ΠΏΡΠΈΠΌΠ΅Π½ΡΠ΅ΠΌΡΠΌ ΠΏΡΠΈ Π»Π΅ΡΠ΅Π½ΠΈΠΈ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ ΠΎΠ½ΠΊΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ. ΠΠ»Π°Π²Π½ΡΠΌ Π½Π΅Π΄ΠΎΡΡΠ°ΡΠΊΠΎΠΌ Π΄ΠΎΠΊΡΠΎΡΡΠ±ΠΈΡΠΈΠ½Π° ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΊΠ°ΡΠ΄ΠΈΠΎΡΠΎΠΊΡΠΈΡΠ½ΠΎΡΡΡ, ΠΌΠ΅Ρ Π°Π½ΠΈΠ·ΠΌ ΠΊΠΎΡΠΎΡΠΎΠΉ Π΄ΠΎ ΠΊΠΎΠ½ΡΠ° Π½Π΅ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ (Minotti et al., 2004). ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΡ ΠΏΠΎΠΊΠ°Π·Π°Π»ΠΈ, ΡΡΠΎ ΠΈΠ½Π³ΠΈΠ±ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΈ ΠΏΠΎΠ΄Π°Π²Π»ΡΠ΅Ρ ΡΠΈΠ³Π½Π°Π» ΠΎ ΠΏΠΎΠ²ΡΠ΅ΠΆΠ΄Π΅Π½ΠΈΡΡ ΠΠΠ Π² ΠΊΠ°ΡΠ΄ΠΈΠΎΠΌΠΈΠΎΡΠΈΡΠ°Ρ (Lyu et al., 2007), ΡΡΠΎ Π³ΠΎΠ²ΠΎΡΠΈΡ ΠΎ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΠΌ ΡΡΠ°ΡΡΠΈΠΈ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ Π² ΠΏΡΠΎΡΠ²Π»Π΅Π½ΠΈΠΈ ΠΊΠ°ΡΠ΄ΠΈΠΎΡΠΎΠΊΡΠΈΡΠ½ΠΎΡΡΠΈ Π΄ΠΎΠΊΡΠΎΡΡΠ±ΠΈΡΠΈΠ½Π°. Π ΡΠ²ΡΠ·ΠΈ Ρ ΡΡΠΈΠΌ ΠΈΠ·ΡΡΠ΅Π½ΠΈΠ΅ Π²ΠΎΠ·Π΄Π΅ΠΉΡΡΠ²ΠΈΡ Π΄ΠΎΠΊΡΠΎΡΡΠ±ΠΈΡΠΈΠ½Π° Π½Π° Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΈ ΠΏΠΎΡΡΡΡΠ°Π½ΡΠ»ΡΡΠΈΠΎΠ½Π½ΡΠ΅ ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΠΈ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»ΡΠ΅Ρ ΠΏΡΠ°ΠΊΡΠΈΡΠ΅ΡΠΊΡΡ ΡΠ΅Π½Π½ΠΎΡΡΡ Π΄Π»Ρ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΠ³ΠΎ ΠΏΡΠ΅Π΄ΠΎΡΠ²ΡΠ°ΡΠ΅Π½ΠΈΡ Π΄Π°Π½Π½ΠΎΠ³ΠΎ ΠΏΠΎΠ±ΠΎΡΠ½ΠΎΠ³ΠΎ Π΄Π΅ΠΉΡΡΠ²ΠΈΡ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ°.
ΠΠ·Π²Π΅ΡΡΠ½ΠΎ, ΡΡΠΎ ΠΏΠΎΠ΄ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ Π΄ΠΎΠΊΡΠΎΡΡΠ±ΠΈΡΠΈΠ½Π° ΠΏΡΠΎΠΈΡΡ ΠΎΠ΄ΠΈΡ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΡ ΡΠ±ΠΈΠΊΠ²ΠΈΡΠΈΠ½-ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌΠ½ΠΎΠΉ ΡΠΈΡΡΠ΅ΠΌΡ ΡΠ°ΡΡΠ΅ΠΏΠ»Π΅Π½ΠΈΡ Π±Π΅Π»ΠΊΠΎΠ² Π½Π° Π½Π΅ΡΠΊΠΎΠ»ΡΠΊΠΈΡ ΡΡΠΎΠ²Π½ΡΡ (Liu et al., 2008). Π ΡΠ°ΡΡΠ½ΠΎΡΡΠΈ, ΠΏΠΎΠ²ΡΡΠ°ΡΡΡΡ ΠΏΠ΅ΠΏΡΠΈΠ΄Π°Π·Π½ΡΠ΅ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠΈ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ. ΠΠ΄Π½Π°ΠΊΠΎ ΠΌΠ΅Ρ Π°Π½ΠΈΠ·ΠΌ ΡΠ΅Π³ΡΠ»ΡΡΠΈΠΈ Π΄Π°Π½Π½ΡΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠ΅ΠΉ ΠΏΡΠΈ Π΄Π΅ΠΉΡΡΠ²ΠΈΠΈ Π½Π° ΠΊΠ»Π΅ΡΠΊΠΈ Π΄ΠΎΠΊΡΠΎΡΡΠ±ΠΈΡΠΈΠ½Π° ΠΎΡΡΠ°ΡΡΡΡ Π½Π΅ΠΈΠ·ΡΡΠ΅Π½Π½ΡΠΌ. ΠΡΡ ΠΎΠ΄Ρ ΠΈΠ· ΡΡΠΎΠ³ΠΎ, ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»ΡΠ΅Ρ ΠΈΠ½ΡΠ΅ΡΠ΅Ρ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡ ΡΠΏΠ΅ΠΊΡΡΠ° ΠΏΠΎΡΡΡΡΠ°Π½ΡΠ»ΡΡΠΈΠΎΠ½Π½ΡΡ ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΠΉ ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ ΠΏΡΠΈ ΠΏΠΎΠ²ΡΠ΅ΠΆΠ΄Π΅Π½ΠΈΠΈ ΠΠΠ Π΄ΠΎΠΊΡΠΎΡΡΠ±ΠΈΡΠΈΠ½ΠΎΠΌ ΠΈ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΠΉ ΡΠ²ΡΠ·ΠΈ ΡΡΠΎΠ³ΠΎ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡ Ρ ΡΠ΅Π³ΡΠ»ΡΡΠΈΠ΅ΠΉ ΠΊΠ°ΡΠ°Π»ΠΈΡΠΈΡΠ΅ΡΠΊΠΈΡ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠ΅ΠΉ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ.
6. ΠΡΠ²ΠΎΠ΄Ρ:
1. Π‘ΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡΡ Π°5, Π°Π± ΠΈ Π°7 ΠΏΠΎΠ΄Π²Π΅ΡΠ³Π°ΡΡΡΡ ΡΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΈ ΡΠ±ΠΈΠΊΠ²ΠΈΡΠΈΠ½ΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ Π562, Π° ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡΠ° pi ΡΠ±ΠΈΠΊΠ²ΠΈΡΠΈΠ½ΠΈΠ»ΠΈΡΡΠ΅ΡΡΡ. Π‘ΠΏΠ΅ΠΊΡΡ ΡΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΈ ΡΠ±ΠΈΠΊΠ²ΠΈΡΠΈΠ½ΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ ΡΠ°Π·Π»ΠΈΡΠ°Π΅ΡΡΡ Π² ΡΠ΄ΡΠ΅ ΠΈ ΡΠΈΡΠΎΠΏΠ»Π°Π·ΠΌΠ΅.
2. ΠΡΠΈ ΠΈΠ½Π΄ΡΠΊΡΠΈΠΈ Π³Π΅Π½ΠΎΡΠΎΠΊΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΡΡΠ΅ΡΡΠ° Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ Π562 Π·Π° ΡΡΡΡ ΠΎΠ±ΡΠ°Π±ΠΎΡΠΊΠΈ Π΄ΠΎΠΊΡΠΎΡΡΠ±ΠΈΡΠΈΠ½ΠΎΠΌ ΡΠΏΠ΅ΠΊΡΡ ΡΠΎΡΡΠΎΡΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΠΈ ΡΠ±ΠΈΠΊΠ²ΠΈΡΠΈΠ½ΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ ΡΡΠ±ΡΠ΅Π΄ΠΈΠ½ΠΈΡ 20S ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ ΡΡΡΠ΅ΡΡΠ²Π΅Π½Π½ΠΎ ΠΈΠ·ΠΌΠ΅Π½ΡΠ΅ΡΡΡ.
3. ΠΠ½Π΄ΡΠΊΡΠΈΡ Π³Π΅Π½ΠΎΡΠΎΠΊΡΠΈΡΠ΅ΡΠΊΠΎΠ³ΠΎ ΡΡΡΠ΅ΡΡΠ° Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ Π562 ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ Π°ΠΊΡΠΈΠ²Π°ΡΠΈΠΈ Ρ ΠΈΠΌΠΎΡΡΠΈΠΏΡΠΈΠ½ΠΎΠΏΠΎΠ΄ΠΎΠ±Π½ΠΎΠΉ ΠΈ ΠΊΠ°ΡΠΏΠ°Π·ΠΎΠΏΠΎΠ΄ΠΎΠ±Π½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠ΅ΠΉ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ.
4. Π£Π±ΠΈΠΊΠ²ΠΈΡΠΈΠ½ΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ in vitro ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡ ΠΊ ΠΏΠΎΠ΄Π°Π²Π»Π΅Π½ΠΈΡ Ρ ΠΈΠΌΠΎΡΡΠΈΠΏΡΠΈΠ½ΠΎΠΏΠΎΠ΄ΠΎΠ±Π½ΠΎΠΉ ΠΈ ΠΊΠ°ΡΠΏΠ°Π·ΠΎΠΏΠΎΠ΄ΠΎΠ±Π½ΠΎΠΉ Π°ΠΊΡΠΈΠ²Π½ΠΎΡΡΠ΅ΠΉ ΠΏΡΠΎΡΠ΅Π°ΡΠΎΠΌ.
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