ΠΠΎΠ»ΡΡΠ΅Π½ΠΈΠ΅ ΠΈ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠ²ΠΎΠΉΡΡΠ² ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² Π°Π½ΡΠΈΡΠ΅Π»Π°, ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ½ΠΎΠ³ΠΎ ΠΊ ΡΠ΅ΡΠ΄Π΅ΡΠ½ΠΎΠΉ ΠΈΠ·ΠΎΡΠΎΡΠΌΠ΅ ΡΡΠΎΠΏΠΎΠ½ΠΈΠ½Π° I
![ΠΠΈΡΡΠ΅ΡΡΠ°ΡΠΈΡ: ΠΠΎΠ»ΡΡΠ΅Π½ΠΈΠ΅ ΠΈ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠ²ΠΎΠΉΡΡΠ² ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ
ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² Π°Π½ΡΠΈΡΠ΅Π»Π°, ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ½ΠΎΠ³ΠΎ ΠΊ ΡΠ΅ΡΠ΄Π΅ΡΠ½ΠΎΠΉ ΠΈΠ·ΠΎΡΠΎΡΠΌΠ΅ ΡΡΠΎΠΏΠΎΠ½ΠΈΠ½Π° I](https://niscu.ru/work/2967236/cover.png)
Π Π΄Π°Π½Π½ΠΎΠΉ ΡΠ°Π±ΠΎΡΠ΅ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΎ ΡΡΠ°Π²Π½Π΅Π½ΠΈΠ΅ ΡΠ²ΠΎΠΉΡΡΠ² ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘7 ΡΠΎ ΡΠ²ΠΎΠΉΡΡΠ²Π°ΠΌΠΈ ΠΈΡΡ ΠΎΠ΄Π½ΠΎΠ³ΠΎ ΠΏΠΎΠ»Π½ΠΎΡΠ°Π·ΠΌΠ΅ΡΠ½ΠΎΠ³ΠΎ Π°Π½ΡΠΈΡΠ΅Π»Π°. Π’Π°ΠΊΠΆΠ΅, Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² Π±ΡΠ»ΠΈ ΡΠΎΠ·Π΄Π°Π½Ρ ΡΠ°Π·Π»ΠΈΡΠ½ΡΠ΅ ΠΌΡΡΠ°Π½ΡΠ½ΡΠ΅ ΡΠΎΡΠΌΡ Ρ ΡΠ΅Π»ΡΡ ΡΠ²Π΅Π»ΠΈΡΠ΅Π½ΠΈΡ Π°ΡΡΠΈΠ½Π½ΠΎΡΡΠΈ ΠΈΡ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΡ Ρ Π°Π½ΡΠΈΠ³Π΅Π½ΠΎΠΌ. ΠΠ»Ρ Π°Π½Π°Π»ΠΈΠ·Π° Π²Π»ΠΈΡΠ½ΠΈΡ ΠΎΡΠ΄Π΅Π»ΡΠ½ΡΡ ΠΌΡΡΠ°ΡΠΈΠΉ Π½Π° Π°ΡΡΠΈΠ½Π½ΠΎΡΡΡ ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ Π°Π½ΡΠΈΡΠ΅Π» Π±ΡΠ» ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ ΡΡΠ°Π²Π½ΠΈΡΠ΅Π»ΡΠ½ΡΠΉ Π°Π½Π°Π»ΠΈΠ· ΠΈΠΌΠΌΡΠ½ΠΎΡ ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΡ … 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΅
- Π‘ΠΏΠΈΡΠΎΠΊ ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΠ΅ΠΌΡΡ ΡΠΎΠΊΡΠ°ΡΠ΅Π½ΠΈΠΉ
- ΠΠ±Π·ΠΎΡ Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΡ
- 1. ΠΠΡ 19Π‘7 ΠΊΠ°ΠΊ Π²Π°ΠΆΠ½ΡΠΉ ΠΈΠ½ΡΡΡΡΠΌΠ΅Π½Ρ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ ΡΡΠΎΠΏΠΎΠ½ΠΈΠ½Π° I Π² ΠΊΡΠΎΠ²ΠΈ
- 2. ΠΠ½ΡΠΈΡΠ΅Π»Π°: ΡΡΡΠΎΠ΅Π½ΠΈΠ΅, ΡΡΠ½ΠΊΡΠΈΠΈ, Π°ΡΡΠΈΠ½Π½ΠΎΠ΅ ΡΠΎΠ·ΡΠ΅Π²Π°Π½ΠΈΠ΅ Π² ΠΎΡΠ³Π°Π½ΠΈΠ·ΠΌΠ΅, ΠΏΡΠ°ΠΊΡΠΈΡΠ΅ΡΠΊΠΎΠ΅ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅
- 2. 1. Π‘ΡΡΠΎΠ΅Π½ΠΈΠ΅ ΠΈΠΌΠΌΡΠ½ΠΎΠ³Π»ΠΎΠ±ΡΠ»ΠΈΠ½ΠΎΠ²
- 2. 2. Π€ΡΠ½ΠΊΡΠΈΠΈ ΠΈΠΌΠΌΡΠ½ΠΎΠ³Π»ΠΎΠ±ΡΠ»ΠΈΠ½ΠΎΠ²
- 2. 3. ΠΡΡΠΈΠ½Π½ΠΎΠ΅ ΡΠΎΠ·ΡΠ΅Π²Π°Π½ΠΈΠ΅ Π°Π½ΡΠΈΡΠ΅Π» Π² ΠΎΡΠ³Π°Π½ΠΈΠ·ΠΌΠ΅
- 2. 4. Π‘ΠΏΠΎΡΠΎΠ±Ρ ΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΡ ΠΈ ΠΏΡΠ°ΠΊΡΠΈΡΠ΅ΡΠΊΠΎΠ΅ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ Π°Π½ΡΠΈΡΠ΅Π»
- 3. Π Π΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΠ΅ Π°Π½ΡΠΈΡΠ΅Π»Π°: ΠΏΡΠΎΠΈΠ·Π²ΠΎΠ΄Π½ΡΠ΅ ΠΈ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΡ, ΠΌΠ΅ΡΠΎΠ΄Ρ ΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΡ, ΠΏΡΠ°ΠΊΡΠΈΡΠ΅ΡΠΊΠΎΠ΅ Π·Π½Π°ΡΠ΅Π½ΠΈΠ΅
- 3. 1. Π’ΠΈΠΏΡ ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² Π°Π½ΡΠΈΡΠ΅Π»
- 3. 2. Π‘ΠΏΠΎΡΠΎΠ±Ρ ΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΡ ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ
Π°Π½ΡΠΈΡΠ΅Π» ΠΈ ΠΈΡ
ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ²
- 3. 2. 1. Π‘ΠΎΠ·Π΄Π°Π½ΠΈΠ΅ ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ Π°Π½Π°Π»ΠΎΠ³ΠΎΠ² Π°Π½ΡΠΈΡΠ΅Π»
- 3. 2. 2. Π‘ΠΎΠ·Π΄Π°Π½ΠΈΠ΅ ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ Π°Π½ΡΠΈΡΠ΅Π» ΠΈ ΠΈΡ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² de novo
- 3. 2. 3. ΠΠΊΡΠΏΡΠ΅ΡΡΠΈΡ ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ Π°Π½ΡΠΈΡΠ΅Π»
- 3. 3. ΠΡΠ°ΠΊΡΠΈΡΠ΅ΡΠΊΠΎΠ΅ ΠΏΡΠΈΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ Π°Π½ΡΠΈΡΠ΅Π»
- 4. Π£Π²Π΅Π»ΠΈΡΠ΅Π½ΠΈΠ΅ Π°ΡΡΠΈΠ½Π½ΠΎΡΡΠΈ Π°Π½ΡΠΈΡΠ΅Π»
- 4. 1. ΠΠ΅ΡΠΎΠ΄Ρ ΡΠ»ΡΡΠ°ΠΉΠ½ΠΎΠ³ΠΎ ΠΌΡΡΠ°Π³Π΅Π½Π΅Π·Π°
- 4. 1. 1. ΠΠ΅Π½Π°ΠΏΡΠ°Π²Π»Π΅Π½Π½ΡΠΉ ΠΌΡΡΠ°Π³Π΅Π½Π΅Π·
- 4. 1. 2. Π£Π²Π΅Π»ΠΈΡΠ΅Π½ΠΈΠ΅ Π°ΡΡΠΈΠ½Π½ΠΎΡΡΠΈ Π°Π½ΡΠΈΡΠ΅Π»Π° ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°ΡΠΈΠΈ
- 4. 2. ΠΠ°ΠΏΡΠ°Π²Π»Π΅Π½Π½ΡΠΉ ΠΌΡΡΠ°Π³Π΅Π½Π΅Π·
- 4. 2. 1. ΠΠΎΠ΄Ρ ΠΎΠ΄Ρ Π΄Π»Ρ Π²ΡΠ±ΠΎΡΠ° Π±ΡΠ΄ΡΡΠΈΡ ΠΌΠΈΡΠ΅Π½Π΅ΠΉ ΠΌΡΡΠ°Π³Π΅Π½Π΅Π·Π°
- 4. 2. 2. ΠΠ΅ΡΠΎΠ΄Ρ Π½Π°ΠΏΡΠ°Π²Π»Π΅Π½Π½ΠΎΠ³ΠΎ ΠΌΡΡΠ°Π³Π΅Π½Π΅Π·Π°
- 4. 1. ΠΠ΅ΡΠΎΠ΄Ρ ΡΠ»ΡΡΠ°ΠΉΠ½ΠΎΠ³ΠΎ ΠΌΡΡΠ°Π³Π΅Π½Π΅Π·Π°
- 5. 1. Π Π΅Π°ΠΊΡΠΈΠ²Ρ ΠΈ ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ Π΄Π»Ρ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ ΡΠ°Π±ΠΎΡ
- 5. 2. Π Π΅Π°ΠΊΡΠΈΠ²Ρ ΠΈ ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ Π΄Π»Ρ Π±ΠΈΠΎΡ ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΡ ΡΠ°Π±ΠΎΡ
- 5. 3. Π Π΅Π°ΠΊΡΠΈΠ²Ρ ΠΈ ΠΌΠ°ΡΠ΅ΡΠΈΠ°Π»Ρ Π΄Π»Ρ ΠΊΡΠ»ΡΡΡΡΠ°Π»ΡΠ½ΠΎ-Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ
- 6. 1. ΠΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΌΠ΅ΡΠΎΠ΄Ρ
- 6. 1. 1. ΠΡΠ΄Π΅Π»Π΅Π½ΠΈΠ΅ ΡΠΎΡΠ°Π»ΡΠ½ΠΎΠΉ Π ΠΠ ΠΈΠ· ΠΊΠ»Π΅ΡΠΎΠΊ Π³ΠΈΠ±ΡΠΈΠ΄ΠΎΠΌΡ, ΠΏΡΠΎΠ΄ΡΡΠΈΡΡΡΡΠΈΡ ΠΠΡ 19Π‘
- 6. 1. 2. ΠΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ Π ΠΠ ΠΈ ΠΠΠ
- 6. 1. 3. ΠΠ±ΡΠ°ΡΠ½Π°Ρ ΡΡΠ°Π½ΡΠΊΡΠΈΠΏΡΠΈΡ
- 6. 1. 4. ΠΠΎΠ»ΠΈΠΌΠ΅ΡΠ°Π·Π½Π°Ρ ΡΠ΅ΠΏΠ½Π°Ρ ΡΠ΅Π°ΠΊΡΠΈΡ
- 6. 1. 5. Π Π΅Π°ΠΊΡΠΈΡ ΡΠ΅ΡΡΡΠΈΠΊΡΠΈΠΈ
- 6. 1. 6. ΠΡΡΠ΅ΠΏΠ»Π΅Π½ΠΈΠ΅ Π½ΡΠΊΠ»Π΅ΠΎΡΠΈΠ΄ΠΎΠ² Ρ Π²ΡΡΡΡΠΏΠ°ΡΡΠΈΡ ΠΎΠ΄Π½ΠΎΠ½ΠΈΡΠ΅Π²ΡΡ ΠΊΠΎΠ½ΡΠΎΠ² ΠΠΠ («Π·Π°ΡΡΠΏΠ»Π΅Π½ΠΈΠ΅ Π»ΠΈΠΏΠΊΠΈΡ ΠΊΠΎΠ½ΡΠΎΠ²»)
- 6. 1. 7. Π Π΅Π°ΠΊΡΠΈΡ Π»ΠΈΠ³ΠΈΡΠΎΠ²Π°Π½ΠΈΡ
- 6. 1. 8. Π’ΡΠ°Π½ΡΡΠΎΡΠΌΠ°ΡΠΈΡ ΠΊΠ»Π΅ΡΠΎΠΊ ΠΈ Π²ΡΡΠ°ΡΠΈΠ²Π°Π½ΠΈΠ΅ Π½ΠΎΡΠ½ΡΡ ΠΊΡΠ»ΡΡΡΡ
- 6. 1. 9. ΠΡΠ΄Π΅Π»Π΅Π½ΠΈΠ΅ ΠΏΠ»Π°Π·ΠΌΠΈΠ΄Π½ΠΎΠΉ ΠΠΠ ΠΈΠ· Π½ΠΎΡΠ½ΠΎΠΉ ΠΊΡΠ»ΡΡΡΡΡ
- 6. 1. 10. ΠΠΊΡΠΏΡΠ΅ΡΡΠΈΡ ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ Fab ΠΈ scFv-ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘7 Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ Π. col
- 6. 2. ΠΠΈΠΎΡ
ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΈ ΠΊΡΠ»ΡΡΡΡΠ°Π»ΡΠ½ΠΎ-Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΌΠ΅ΡΠΎΠ΄Ρ
- 6. 2. 1. ΠΡΠΈΠ³ΠΎΡΠΎΠ²Π»Π΅Π½ΠΈΠ΅ ΠΎΠ±ΡΠ°Π·ΡΠΎΠ² Π΄Π»Ρ ΠΠ‘Π ΡΠ»Π΅ΠΊΡΡΠΎΡΠΎΡΠ΅Π·Π°
- 6. 2. 2. ΠΠ‘Π ΡΠ»Π΅ΠΊΡΡΠΎΡΠΎΡΠ΅Π· Π² ΠΏΠΎΠ»ΠΈΠ°ΠΊΡΠΈΠ»Π°ΠΌΠΈΠ΄Π½ΠΎΠΌ Π³Π΅Π»Π΅
- 6. 2. 3. Π‘ΠΏΠ΅ΠΊΡΡΠΎΡΠΎΡΠΎΠΌΠ΅ΡΡΠΈΡΠ΅ΡΠΊΠΎΠ΅ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ Π±Π΅Π»ΠΊΠ° (OD280)
- 6. 2. 4. ΠΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ Π±Π΅Π»ΠΊΠ° ΠΏΠΎ ΠΌΠ΅ΡΠΎΠ΄Ρ ΠΠΎΡΡΠΈ
- 6. 2. 5. ΠΡΠ»ΡΡΠΈΠ²ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΠΊΠ»Π΅ΡΠΎΠΊ Π³ΠΈΠ±ΡΠΈΠ΄ΠΎΠΌΡ, ΠΏΡΠΎΠ΄ΡΡΠΈΡΡΡΡΠΈΡ ΠΠΡ 19Π‘
- 6. 2. 6. ΠΡΠ΄Π΅Π»Π΅Π½ΠΈΠ΅ ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘
- 6. 2. 7. Π Π΅Π½Π°ΡΡΡΠ°ΡΠΈΡ ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘
- 6. 2. 8. ΠΡΡΠΈΠ½Π½Π°Ρ ΠΎΡΠΈΡΡΠΊΠ° ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘
- 6. 2. 9. ΠΠ΅Π»ΡΡΠΈΠ»ΡΡΡΠ°ΡΠΈΠΎΠ½Π½Π°Ρ Ρ ΡΠΎΠΌΠ°ΡΠΎΠ³ΡΠ°ΡΠΈΡ
- 6. 2. 10. ΠΠΎΠ½ΡΠ΅Π½ΡΡΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ ΠΏΡΠΎΠ± ΠΠΡ 19Π‘7 ΠΈ Π΅Π³ΠΎ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ²
- 6. 2. 11. ΠΠΎΠ½ΡΡΠ³ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π½ΠΎΡΠΈΡΠ΅Π»Ρ Sulfolink Ρ ΠΏΠ΅ΠΏΡΠΈΠ΄ΠΎΠΌ Tn
- 6. 3. ΠΠΌΠΌΡΠ½ΠΎΡ
ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΌΠ΅ΡΠΎΠ΄Ρ
- 6. 3. 1. ΠΠΌΠΌΡΠ½ΠΎΠ±Π»ΠΎΡΡΠΈΠ½Π³
- 6. 3. 2. ΠΠΌΠΌΡΠ½ΠΎΡΠ΅ΡΠΌΠ΅Π½ΡΠ½ΡΠΉ Π°Π½Π°Π»ΠΈΠ· (ΠΠ€Π)
- 6. 3. 2. Π€Π»ΡΠΎΡΠΎΠΈΠΌΠΌΡΠ½Π½ΡΠΉ Π°Π½Π°Π»ΠΈΠ· (Π€ΠΠ) «ΡΡΠ½Π΄Π²ΠΈΡ"-ΡΠΈΠΏΠ°
- 6. 3. 3. ΠΠΈΠΎΡΠΈΠ½ΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π°Π½ΡΠΈΡΠ΅Π», ΠΈΡ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΈ Π°Π½ΡΠΈΠ³Π΅Π½Π°
- 6. 3. 4. ΠΠΎΠ»ΡΡΠ΅Π½ΠΈΠ΅ Fab-ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΈΠ· ΠΏΠΎΠ»Π½ΠΎΡΠ°Π·ΠΌΠ΅ΡΠ½ΠΎΠ³ΠΎ ΠΠΡ 19Π‘7 ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΏΡΠΎΡΠ΅ΠΎΠ»ΠΈΠ·Π° ΠΏΠΎΠ΄ Π΄Π΅ΠΉΡΡΠ²ΠΈΠ΅ΠΌ ΠΏΠ°ΠΏΠ°ΠΈΠ½Π°
- 6. 3. 5. ΠΠ·ΠΌΠ΅ΡΠ΅Π½ΠΈΠ΅ ΠΏΠ°ΡΠ°ΠΌΠ΅ΡΡΠΎΠ² ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΡ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΈ ΠΏΠΎΠ»Π½ΠΎΡΠ°Π·ΠΌΠ΅ΡΠ½ΠΎΠ³ΠΎ ΠΠΡ 19Π‘7 Ρ ΡΡΠΎΠΏΠΎΠ½ΠΈΠ½ΠΎΠ²ΡΠΌ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠΎΠΌ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΏΠΎΠ²Π΅ΡΡ Π½ΠΎΡΡΠ½ΠΎΠ³ΠΎ ΠΏΠ»Π°Π·ΠΌΠΎΠ½Π½ΠΎΠ³ΠΎ ΡΠ΅Π·ΠΎΠ½Π°Π½ΡΠ° (SPR)
- 6. 3. 6. ΠΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ ΡΡΠ°Π±ΠΈΠ»ΡΠ½ΠΎΡΡΠΈ rFab, eFab ΠΈ ΠΏΠΎΠ»Π½ΠΎΡΠ°Π·ΠΌΠ΅ΡΠ½ΠΎΠ³ΠΎ ΠΠΡ 19Π‘
- 6. 4. ΠΠΎΠ΄Π΅Π»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ in silico ΠΌΡΡΠ°Π³Π΅Π½Π΅Π·Π° Fv-ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘
- 6. 5. Π€Π°Π³ΠΎΠ²ΡΠΉ Π΄ΠΈΡΠΏΠ»Π΅ΠΉ
- 6. 5. 1. ΠΠ°ΡΠ°ΡΠΈΠ²Π°Π½ΠΈΠ΅ ΠΈ Π²ΡΠ΄Π΅Π»Π΅Π½ΠΈΠ΅ ΡΠ°Π³ΠΎΠ²ΡΡ ΡΠ°ΡΡΠΈΡ
- 6. 5. 2. ΠΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ ΡΠ°Π³ΠΎΠ²ΡΡ ΡΠ°ΡΡΠΈΡ
- 6. 5. 3. Π Π°Π·Π»ΠΈΡΠ½ΡΠ΅ ΡΠΏΠΎΡΠΎΠ±Ρ ΠΎΡΠ±ΠΎΡΠ° ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΡΠ°Π³ΠΎΠ²ΠΎΠ³ΠΎ Π΄ΠΈΡΠΏΠ»Π΅Ρ
- 7. 1. ΠΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ Π½ΡΠΊΠ»Π΅ΠΎΡΠΈΠ΄Π½ΠΎΠΉ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΠΈ, ΡΠΎΠΎΡΠ²Π΅ΡΡΡΠ²ΡΡΡΠ΅ΠΉ ΠΠ¦ ΠΈ ΡΠ’Π¦ ΠΠΡ 19Π‘
- 7. 2. ΠΠΎΠ»ΡΡΠ΅Π½ΠΈΠ΅ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΉ Π΄Π»Ρ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ ΠΠ¦ ΠΈ ΡΠ’Π¦ ΠΠΡ 19Π‘
- 7. 3. ΠΠΊΡΠΏΡΠ΅ΡΡΠΈΡ ΠΈ Π»ΠΎΠΊΠ°Π»ΠΈΠ·Π°ΡΠΈΡ ΠΠ¦ ΠΈ ΡΠ’Π¦ ΠΠΡ 19Π‘7 Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ
Π. coli ΡΡΠ°ΠΌΠΌΠ° BL21pLysS
- 7. 3. 1. ΠΠΊΡΠΏΡΠ΅ΡΡΠΈΡ ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ ΠΠ¦ ΠΈ ΡΠ’Π¦ ΠΠΡ 19Π‘7 Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ Π. coli ΡΡΠ°ΠΌΠΌΠ° BL21pLysS
- 7. 3. 2. ΠΠ·ΡΡΠ΅Π½ΠΈΠ΅ Π²Π½ΡΡΡΠΈΠΊΠ»Π΅ΡΠΎΡΠ½ΠΎΠΉ Π»ΠΎΠΊΠ°Π»ΠΈΠ·Π°ΡΠΈΠΈ ΠΠ¦ ΠΈ ΡΠ’Π¦ ΠΠΡ 19Π‘
- 7. 4. ΠΠΎΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΈΠ΅ Π³Π΅ΡΠ΅ΡΠΎΠ΄ΠΈΠΌΠ΅ΡΠ½ΠΎΠΉ ΡΡΡΡΠΊΡΡΡΡ rFab-ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘7 ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΡΠ΅Π½Π°ΡΡΡΠ°ΡΠΈΠΈ
- 7. 4. 1. ΠΠ΅Π½Π°ΡΡΡΠ°ΡΠΈΡ ΠΠ¦ ΠΈ ΡΠ’Π¦ ΠΈ ΡΠ΅Π½Π°ΡΡΡΠ°ΡΠΈΡ rFab-ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘
- 7. 4. 2. ΠΠΏΡΠΈΠΌΠΈΠ·Π°ΡΠΈΡ ΡΡΠ»ΠΎΠ²ΠΈΠΉ ΡΠ΅Π½Π°ΡΡΡΠ°ΡΠΈΠΈ rFab-ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘
- 7. 4. 3. ΠΡΠΈΡΡΠΊΠ° rFab-ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘7 ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ Π°ΡΠΈΠ½Π½ΠΎΠΉ Ρ ΡΠΎΠΌΠ°ΡΠΎΠ³ΡΠ°ΡΠΈΠΈ ΠΈ Ρ Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠ° ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΠΎΠ³ΠΎ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ°
- 8. 1. ΠΠΎΠ»ΡΡΠ΅Π½ΠΈΠ΅ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΈ Π΄Π»Ρ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ rFab-ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘7 Π² ΠΏΠ΅ΡΠΈΠΏΠ»Π°Π·ΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠΌ ΠΏΡΠΎΡΡΡΠ°Π½ΡΡΠ²Π΅ ΠΊΠ»Π΅ΡΠΎΠΊ Π. col
- 8. 2. ΠΠΏΡΠΈΠΌΠΈΠ·Π°ΡΠΈΡ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π° ΡΡΠ½ΠΊΡΠΈΠΎΠ½Π°Π»ΡΠ½ΠΎ-Π°ΠΊΡΠΈΠ²Π½ΡΡ rFab-ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘7, ΠΏΠΎΠ»ΡΡΠ°Π΅ΠΌΠΎΠ³ΠΎ ΠΏΡΠΈ ΠΏΠ΅ΡΠΈΠΏΠ»Π°Π·ΠΌΠ°ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ
- 8. 3. ΠΡΠΈΡΡΠΊΠ° rFab-ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘7 ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ Π°ΡΡΠΈΠ½Π½ΠΎΠΉ Ρ ΡΠΎΠΌΠ°ΡΠΎΠ³ΡΠ°ΡΠΈΠΈ ΠΈ Ρ Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΡΡΠΈΠΊΠ° ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΠ°
- 9. 1. ΠΠΎΠ»ΡΡΠ΅Π½ΠΈΠ΅ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΡ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΉ Π΄Π»Ρ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ scFv-ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘
- 9. 2. ΠΠΊΡΠΏΡΠ΅ΡΡΠΈΡ ΠΈ Π»ΠΎΠΊΠ°Π»ΠΈΠ·Π°ΡΠΈΡ scFv-ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘7 Π² ΠΊΠ»Π΅ΡΠΊΠ°Ρ Π. col
- 9. 3. ΠΠΎΡΡΡΠ°Π½ΠΎΠ²Π»Π΅Π½ΠΈΠ΅ ΡΡΡΡΠΊΡΡΡΡ scFv-ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘7 ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΡΠ΅Π½Π°ΡΡΡΠ°ΡΠΈΠΈ ΠΈ ΠΈΡ ΠΎΡΠΈΡΡΠΊΠ° ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ Π°ΡΠΈΠ½Π½ΠΎΠΉ Ρ ΡΠΎΠΌΠ°ΡΠΎΠ³ΡΠ°ΡΠΈΠΈ
- 10. 1. ΠΠ½Π°Π»ΠΈΠ· ΡΠ»Π΅ΠΊΡΡΠΎΡΠΎΡΠ΅ΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΏΠΎΠ΄Π²ΠΈΠΆΠ½ΠΎΡΡΠΈ ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘
- 10. 2. ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΠΈΠΌΠΌΡΠ½ΠΎΡ ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΡ ΡΠ²ΠΎΠΉΡΡΠ² ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘7 ΠΌΠ΅ΡΠΎΠ΄Π°ΠΌΠΈ Π€ΠΠ ΠΈ ΠΠ€Π
- 10. 3. ΠΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΠΊΠΈΠ½Π΅ΡΠΈΠΊΠΈ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΡ rFab-ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘7 ΠΈ hcTnl ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΏΠΎΠ²Π΅ΡΡ Π½ΠΎΡΡΠ½ΠΎΠ³ΠΎ ΠΏΠ»Π°Π·ΠΌΠΎΠ½Π½ΠΎΠ³ΠΎ ΡΠ΅Π·ΠΎΠ½Π°Π½ΡΠ°
- 10. 4. Π‘ΡΠ°Π²Π½Π΅Π½ΠΈΠ΅ ΡΡΠ°Π±ΠΈΠ»ΡΠ½ΠΎΡΡΠΈ ΠΏΠΎΠ»Π½ΠΎΡΠ°Π·ΠΌΠ΅ΡΠ½ΡΡ ΠΠΡ 19Π‘7 ΠΈ ΠΈΡ ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ²
- 10. 5. ΠΠ·ΡΡΠ΅Π½ΠΈΠ΅ ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΠΈ ΠΊ ΡΠΎΡΠ±ΡΠΈΠΈ Π½Π° ΠΏΠΎΠ²Π΅ΡΡ Π½ΠΎΡΡΠΈ ΠΏΠ»Π°Π½ΡΠ΅ΡΠ° ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘7 Π² ΡΡΠ°Π²Π½Π΅Π½ΠΈΠΈ Ρ ΠΏΠΎΠ»Π½ΠΎΡΠ°Π·ΠΌΠ΅ΡΠ½ΡΠΌΠΈ ΠΠΡ 19Π‘7 ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ Π€ΠΠ
- 11. 1. ΠΠΎΠ΄Π±ΠΎΡ ΡΡΠ»ΠΎΠ²ΠΈΠΉ Π΄Π»Ρ ΡΡΡΠ΅ΠΊΡΠΈΠ²Π½ΠΎΠ³ΠΎ Π±ΠΈΠΎΡΠΈΠ½ΠΈΠ»ΠΈΡΠΎΠ²Π°Π½ΠΈΡ rFab-ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘
- 11. 2. Π‘ΡΠ°Π²Π½Π΅Π½ΠΈΠ΅ ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΠΈ ΠΊ ΡΠΎΡΠ±ΡΠΈΠΈ Π½Π° ΠΏΠΎΠ²Π΅ΡΡ Π½ΠΎΡΡΠΈ ΠΏΠ»Π°Π½ΡΠ΅ΡΠ° Π±ΠΈΠΎΡΠΈΠ½ΠΈΠ»ΠΈΡΠΎΠ²Π°Π½Π½ΡΡ ΠΠΡ 19Π‘7 ΠΈ ΠΈΡ ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ²
- 12. 1. ΠΡΠ±ΠΎΡ in silico ΠΌΡΡΠ°Π½ΡΠ½ΡΡ scFv-ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘
- 12. 2. ΠΡΠ±ΠΎΡ ΠΌΡΡΠ°Π½ΡΠ½ΡΡ
scFv-ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘7 ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΡΠ°Π³ΠΎΠ²ΠΎΠ³ΠΎ Π΄ΠΈΡΠΏΠ»Π΅Ρ
- 12. 2. 1. ΠΠ»ΠΎΠ½ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π±ΠΈΠ±Π»ΠΈΠΎΡΠ΅ΠΊΠΈ ΠΌΡΡΠΈΡΠΎΠ²Π°Π½Π½ΡΡ Π³Π΅Π½ΠΎΠ² scFv-ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘7, ΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΠ΅ ΡΠ°Π³ΠΎΠ²ΡΡ ΡΠ°ΡΡΠΈΡ
- 12. 2. 2. ΠΠΎΠ΄Π±ΠΎΡ ΡΡΠ»ΠΎΠ²ΠΈΠΉ ΠΈ ΠΎΡΡΡΠ΅ΡΡΠ²Π»Π΅Π½ΠΈΠ΅ ΠΎΡΠ±ΠΎΡΠ° ΠΌΡΡΠ°Π½ΡΠ½ΡΡ scFv-ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘7 ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΡΠ°Π³ΠΎΠ²ΠΎΠ³ΠΎ Π΄ΠΈΡΠΏΠ»Π΅Ρ
- 12. 3. Π₯Π°ΡΠ°ΠΊΡΠ΅ΡΠΈΠ·Π°ΡΠΈΡ ΠΊΠ»ΠΎΠ½ΠΎΠ² ΠΌΡΡΠ°Π½ΡΠ½ΡΡ
scFv-ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘
- 12. 3. 1. Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ Π°ΡΡΠΈΠ½Π½ΠΎΡΡΠΈ ΠΌΡΡΠ°Π½ΡΠ½ΡΡ Π²Π°ΡΠΈΠ°Π½ΡΠΎΠ² scFv-ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘7, ΠΏΡΠ΅Π΄ΡΠΊΠ°Π·Π°Π½Π½ΡΡ in silico
- 12. 3. 2. Π Π΅Π·ΡΠ»ΡΡΠ°ΡΡ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ Π°ΡΡΠΈΠ½Π½ΠΎΡΡΠΈ ΠΌΡΡΠ°Π½ΡΠ½ΡΡ scFv-ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘7, ΠΎΡΠΎΠ±ΡΠ°Π½Π½ΡΡ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΡΠ°Π³ΠΎΠ²ΠΎΠ³ΠΎ Π΄ΠΈΡΠΏΠ»Π΅Ρ
ΠΠΎΠ»ΡΡΠ΅Π½ΠΈΠ΅ ΠΈ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠ²ΠΎΠΉΡΡΠ² ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² Π°Π½ΡΠΈΡΠ΅Π»Π°, ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ½ΠΎΠ³ΠΎ ΠΊ ΡΠ΅ΡΠ΄Π΅ΡΠ½ΠΎΠΉ ΠΈΠ·ΠΎΡΠΎΡΠΌΠ΅ ΡΡΠΎΠΏΠΎΠ½ΠΈΠ½Π° I (ΡΠ΅ΡΠ΅ΡΠ°Ρ, ΠΊΡΡΡΠΎΠ²Π°Ρ, Π΄ΠΈΠΏΠ»ΠΎΠΌ, ΠΊΠΎΠ½ΡΡΠΎΠ»ΡΠ½Π°Ρ)
Π‘Π΅ΡΠ΄Π΅ΡΠ½ΠΎ-ΡΠΎΡΡΠ΄ΠΈΡΡΡΠ΅ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ ΠΎΡΡΠ°ΡΡΡΡ Π³Π»Π°Π²Π½ΠΎΠΉ ΠΏΡΠΈΡΠΈΠ½ΠΎΠΉ Π²ΡΡΠΎΠΊΠΎΠΉ ΡΠΌΠ΅ΡΡΠ½ΠΎΡΡΠΈ Π² Π ΠΎΡΡΠΈΠΈ ΠΈ Π΄ΡΡΠ³ΠΈΡ ΠΈΠ½Π΄ΡΡΡΡΠΈΠ°Π»ΡΠ½ΠΎ-ΡΠ°Π·Π²ΠΈΡΡΡ ΡΡΡΠ°Π½Π°Ρ . ΠΠ½ΠΈ ΡΠ²Π»ΡΡΡΡΡ ΠΎΠ΄Π½ΠΈΠΌΠΈ ΠΈΠ· Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ ΡΠ°ΡΠΏΡΠΎΡΡΡΠ°Π½Π΅Π½Π½ΡΡ ΠΈ Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ ΠΎΠΏΠ°ΡΠ½ΡΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ Π² ΠΌΠΈΡΠ΅. ΠΠΎ Π΄Π°Π½Π½ΡΠΌ ΠΡΠ΅ΠΌΠΈΡΠ½ΠΎΠΉ ΠΡΠ³Π°Π½ΠΈΠ·Π°ΡΠΈΠΈ ΠΠ΄ΡΠ°Π²ΠΎΠΎΡ ΡΠ°Π½Π΅Π½ΠΈΡ Π² 2008 Π³ΠΎΠ΄Ρ ΡΠ΅ΡΠ΄Π΅ΡΠ½ΠΎ-ΡΠΎΡΡΠ΄ΠΈΡΡΡΠ΅ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ ΠΏΡΠΈΠ²Π΅Π»ΠΈ ΠΊ ΡΠΌΠ΅ΡΡΠΈ 17.3 ΠΌΠΈΠ»Π»ΠΈΠΎΠ½ΠΎΠ² ΡΠ΅Π»ΠΎΠ²Π΅ΠΊ, ΡΡΠΎ ΡΠΎΡΡΠ°Π²ΠΈΠ»ΠΎ 30% Π²ΡΠ΅Ρ ΡΠ»ΡΡΠ°Π΅Π² ΡΠΌΠ΅ΡΡΠΈ Π² ΠΌΠΈΡΠ΅. ΠΠ· Π½ΠΈΡ 6.2 ΠΌΠΈΠ»Π»ΠΈΠΎΠ½Π° ΡΠ΅Π»ΠΎΠ²Π΅ΠΊ ΡΠΌΠ΅ΡΠ»ΠΈ ΠΎΡ ΠΈΠ½ΡΠ°ΡΠΊΡΠ° ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π°. ΠΡΠ½ΠΎΠ²Π½ΡΠΌΠΈ ΠΌΠ΅ΡΠΎΠ΄Π°ΠΌΠΈ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ ΡΠ΅ΡΠ΄ΡΠ° ΡΠ²Π»ΡΡΡΡΡ ΡΠΈΠ·ΠΈΡΠ΅ΡΠΊΠΎΠ΅ ΠΎΠ±ΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠ΅, ΡΠ»Π΅ΠΊΡΡΠΎΠΊΠ°ΡΠ΄ΠΈΠΎΠ³ΡΠ°ΡΠΈΡ ΠΈ ΠΈΠ·ΡΡΠ΅Π½ΠΈΠ΅ Π±ΠΈΠΎΡ ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΡ ΠΌΠ°ΡΠΊΠ΅ΡΠΎΠ² ΠΏΠΎΠ²ΡΠ΅ΠΆΠ΄Π΅Π½ΠΈΡ ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π°.
ΠΠΌΠΌΡΠ½ΠΎΡ ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΌΠ΅ΡΠΎΠ΄Ρ ΡΠ²Π»ΡΡΡΡΡ Π²Π°ΠΆΠ½ΡΠΌ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΡΠ΅ΡΠΊΠΈΠΌ ΠΈΠ½ΡΡΡΡΠΌΠ΅Π½ΡΠΎΠΌ ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΡ Π±Π΅Π»ΠΊΠΎΠ²ΡΡ ΠΌΠ°ΡΠΊΠ΅ΡΠΎΠ² ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ. ΠΡΠΊΡΡΡΠΈΠ΅ ΠΌΠ΅ΡΠΎΠ΄Π° ΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΡ ΠΌΠΎΠ½ΠΎΠΊΠ»ΠΎΠ½Π°Π»ΡΠ½ΡΡ Π°Π½ΡΠΈΡΠ΅Π» Ρ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ Π³ΠΈΠ±ΡΠΈΠ΄ΠΎΠΌΠ½ΠΎΠΉ ΡΠ΅Ρ Π½ΠΎΠ»ΠΎΠ³ΠΈΠΈ ΠΠ΅Π»Π»Π΅ΡΠΎΠΌ ΠΈ ΠΠΈΠ»ΡΡΡΠ΅ΠΉΠ½ΠΎΠΌ Π² 1975 Π³ΠΎΠ΄Ρ ΠΎΠΊΠ°Π·Π°Π»ΠΎ ΠΎΠ³ΡΠΎΠΌΠ½ΠΎΠ΅ Π²Π»ΠΈΡΠ½ΠΈΠ΅ Π½Π° ΡΠ°Π·Π²ΠΈΡΠΈΠ΅ ΡΡΠ½Π΄Π°ΠΌΠ΅Π½ΡΠ°Π»ΡΠ½ΠΎΠΉ Π½Π°ΡΠΊΠΈ ΠΈ ΠΊΠ»ΠΈΠ½ΠΈΡΠ΅ΡΠΊΠΎΠΉ ΠΏΡΠ°ΠΊΡΠΈΠΊΠΈ. ΠΠ»Π°Π³ΠΎΠ΄Π°ΡΡ ΡΠ½ΠΈΠΊΠ°Π»ΡΠ½ΠΎΠΌΡ ΡΠ²ΠΎΠΉΡΡΠ²Ρ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ½ΠΎ ΠΈ Ρ Π²ΡΡΠΎΠΊΠΈΠΌ ΡΡΠΎΠ΄ΡΡΠ²ΠΎΠΌ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΎΠ²Π°ΡΡ Ρ Π°Π½ΡΠΈΠ³Π΅Π½Π°ΠΌΠΈ, ΠΌΠΎΠ½ΠΎΠΊΠ»ΠΎΠ½Π°Π»ΡΠ½ΡΠ΅ Π°Π½ΡΠΈΡΠ΅Π»Π° Π½Π°ΡΠ°Π»ΠΈ Π°ΠΊΡΠΈΠ²Π½ΠΎ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°ΡΡ Π΄Π»Ρ Π½Π°ΡΡΠ½ΡΡ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°Π½ΠΈΠΉ ΠΈ ΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ. ΠΠ° ΡΠ΅Π³ΠΎΠ΄Π½ΡΡΠ½ΠΈΠΉ Π΄Π΅Π½Ρ, Π°Π½ΡΠΈΡΠ΅Π»Π° ΡΠΎΡΡΠ°Π²Π»ΡΡΡ ΠΏΡΠΈΠ±Π»ΠΈΠ·ΠΈΡΠ΅Π»ΡΠ½ΠΎ ΠΎΠ΄Π½Ρ ΡΡΠ΅ΡΡ ΠΎΡ ΠΎΠ±ΡΠ΅Π³ΠΎ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π° Π±Π΅Π»ΠΊΠΎΠ², ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΠ΅ΠΌΡΡ Π² ΡΠ΅ΡΠ°ΠΏΠΈΠΈ ΡΠ°Π·Π»ΠΈΡΠ½ΡΡ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΠΉ Π² ΡΠ°Π·Π²ΠΈΡΡΡ ΡΡΡΠ°Π½Π°Ρ [1].
ΠΠ·ΠΎΡΠΎΡΠΌΠ° ΡΡΠΎΠΏΠΎΠ½ΠΈΠ½Π° I ΠΈΠ· ΡΠ΅ΡΠ΄ΡΠ° ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ° (hcTnl) ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»ΡΠ΅Ρ ΡΠΎΠ±ΠΎΠΉ ΡΠ°Π½Π½ΠΈΠΉ ΠΈ Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ ΡΠΏΠ΅ΡΠΈΡΠΈΡΠ΅ΡΠΊΠΈΠΉ ΠΌΠ°ΡΠΊΠ΅Ρ ΠΏΠΎΠ²ΡΠ΅ΠΆΠ΄Π΅Π½ΠΈΡ ΠΊΠ°ΡΠ΄ΠΈΠΎΠΌΠΈΠΎΡΠΈΡΠΎΠ², ΡΠΎΠΏΡΠΎΠ²ΠΎΠΆΠ΄Π°ΡΡΠ΅Π³ΠΎ ΡΠ°ΠΊΠΈΠ΅ ΡΠ΅ΡΡΠ΅Π·Π½ΡΠ΅ ΡΠ΅ΡΠ΄Π΅ΡΠ½ΠΎ-ΡΠΎΡΡΠ΄ΠΈΡΡΡΠ΅ Π·Π°Π±ΠΎΠ»Π΅Π²Π°Π½ΠΈΡ, ΠΊΠ°ΠΊ ΠΈΠ½ΡΠ°ΡΠΊΡ ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π° ΠΈ Π½Π΅ΡΡΠ°Π±ΠΈΠ»ΡΠ½Π°Ρ ΡΡΠ΅Π½ΠΎΠΊΠ°ΡΠ΄ΠΈΡ. ΠΡΠΎΠΌΠ΅ ΡΠΎΠ³ΠΎ, ΠΏΠΎΠ²ΡΡΠ΅Π½ΠΈΠ΅ ΡΡΠΎΠ²Π½Ρ ΡΡΠΎΠΏΠΎΠ½ΠΈΠ½Π° I Π² ΠΊΡΠΎΠ²ΠΈ ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΠ΅ΡΡΡ Π΄Π»Ρ ΠΎΡΠ΅Π½ΠΊΠΈ ΡΠΈΡΠΊΠ° ΠΎΡΠ»ΠΎΠΆΠ½Π΅Π½ΠΈΠΉ Ρ ΠΎΡΡΡΡΠΌ ΠΊΠΎΡΠΎΠ½Π°ΡΠ½ΡΠΌ ΡΠΈΠ½Π΄ΡΠΎΠΌΠΎΠΌ ΠΈ ΠΎΠΏΡΠΈΠΌΠΈΠ·Π°ΡΠΈΠΈ Π»Π΅ΡΠ΅Π±Π½ΡΡ ΠΌΠ΅ΡΠΎΠΏΡΠΈΡΡΠΈΠΉ. Π‘ΠΎΠ·Π΄Π°Π½ΠΈΠ΅ Π½ΠΎΠ²ΡΡ ΠΈ ΡΡΠΎΠ²Π΅ΡΡΠ΅Π½ΡΡΠ²ΠΎΠ²Π°Π½ΠΈΠ΅ ΡΠΆΠ΅ ΡΡΡΠ΅ΡΡΠ²ΡΡΡΠΈΡ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΡΠ΅ΡΠΊΠΈΡ ΡΠΈΡΡΠ΅ΠΌ, ΠΎΡΠ½ΠΎΠ²Π°Π½Π½ΡΡ Π½Π° ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠΈ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ hcTnl Π² ΠΊΡΠΎΠ²ΠΈ, ΡΠ²Π»ΡΠ΅ΡΡΡ ΠΎΠ΄Π½ΠΎΠΉ ΠΈΠ· Π°ΠΊΡΡΠ°Π»ΡΠ½ΡΡ Π·Π°Π΄Π°Ρ Π±ΠΈΠΎΠΌΠ΅Π΄ΠΈΡΠΈΠ½ΡΠΊΠΎΠΉ Ρ ΠΈΠΌΠΈΠΈ.
ΠΠΎΠ½ΠΎΠΊΠ»ΠΎΠ½Π°Π»ΡΠ½ΠΎΠ΅ Π°Π½ΡΠΈΡΠ΅Π»ΠΎ 19Π‘7 (ΠΠΡ 19Π‘7) Ρ Π²ΡΡΠΎΠΊΠΎΠΉ Π°ΡΡΠΈΠ½Π½ΠΎΡΡΡΡ ΡΠ°ΡΠΏΠΎΠ·Π½Π°Π΅Ρ hcTnl ΠΈ ΠΌΠΎΠΆΠ΅Ρ Π±ΡΡΡ ΠΈΡΠΏΠΎΠ»ΡΠ·ΠΎΠ²Π°Π½ΠΎ Π΄Π»Ρ ΡΠΎΠ·Π΄Π°Π½ΠΈΡ ΠΌΠ½ΠΎΠ³ΠΈΡ ΡΠΈΡΡΠ΅ΠΌ Π΄ΠΈΠ°Π³Π½ΠΎΡΡΠΈΠΊΠΈ ΠΈΠ½ΡΠ°ΡΠΊΡΠ° ΠΌΠΈΠΎΠΊΠ°ΡΠ΄Π°, ΠΎΡΠ½ΠΎΠ²Π°Π½Π½ΡΡ Π½Π° ΠΎΠΏΡΠ΅Π΄Π΅Π»Π΅Π½ΠΈΠΈ ΠΊΠΎΠ½ΡΠ΅Π½ΡΡΠ°ΡΠΈΠΈ hcTnl Π² ΠΊΡΠΎΠ²ΠΈ. ΠΠ΄Π½Π°ΠΊΠΎ Π°Π½ΡΠΈΡΠ΅Π»Π°, ΠΏΠΎΠ»ΡΡΠ°Π΅ΠΌΡΠ΅ Π³ΠΈΠ±ΡΠΈΠ΄ΠΎΠΌΠ½ΡΠΌ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΈ ΠΎΡΠΈΡΠ°Π΅ΠΌΡΠ΅ ΠΎΠ±ΡΡΠ½ΠΎ Π½Π° Ρ ΡΠΎΠΌΠ°ΡΠΎΠ³ΡΠ°ΡΠΈΡΠ΅ΡΠΊΠΈΡ Π½ΠΎΡΠΈΡΠ΅Π»ΡΡ Ρ ΠΈΠΌΠΌΠΎΠ±ΠΈΠ»ΠΈΠ·ΠΎΠ²Π°Π½Π½ΡΠΌ Π±Π΅Π»ΠΊΠΎΠΌ, Π ΠΈΠ· Staphylococcus aureus, ΡΠΎΠ΄Π΅ΡΠΆΠ°Ρ ΠΏΡΠΈΠΌΠ΅ΡΠΈ ΠΈΠΌΠΌΡΠ½ΠΎΠ³Π»ΠΎΠ±ΡΠ»ΠΈΠ½ΠΎΠ² ΠΌΡΡΠΈ, ΠΊΠΎΡΠΎΡΡΠ΅ ΠΌΠΎΠ³ΡΡ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΎΠ²Π°ΡΡ Ρ Π΄ΡΡΠ³ΠΈΠΌΠΈ Π°Π½ΡΠΈΠ³Π΅Π½Π°ΠΌΠΈ Π² Π°Π½Π°Π»ΠΈΠ·ΠΈΡΡΠ΅ΠΌΡΡ ΠΆΠΈΠ΄ΠΊΠΎΡΡΡΡ , ΡΡΠΎ ΠΌΠΎΠΆΠ΅Ρ ΠΏΡΠΈΠ²ΠΎΠ΄ΠΈΡΡ ΠΊ Π»ΠΎΠΆΠ½ΠΎΠΏΠΎΠ»ΠΎΠΆΠΈΡΠ΅Π»ΡΠ½ΡΠΌ ΡΠ΅Π·ΡΠ»ΡΡΠ°ΡΠ°ΠΌ Π΄Π΅ΡΠ΅ΠΊΡΠΈΠΈ ΠΈΡΡΠ»Π΅Π΄ΡΠ΅ΠΌΠΎΠ³ΠΎ Π°Π½ΡΠΈΠ³Π΅Π½Π°.
ΠΠ»ΡΡΠ΅ΡΠ½Π°ΡΠΈΠ²Π½ΡΠΌ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΠΏΠΎΠ»ΡΡΠ΅Π½ΠΈΡ Π°Π½ΡΠΈΡΠ΅Π» ΡΠ²Π»ΡΠ΅ΡΡΡ ΡΠΎΠ·Π΄Π°Π½ΠΈΠ΅ ΠΈΡ ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ Π°Π½Π°Π»ΠΎΠ³ΠΎΠ². ΠΡΠΎΡ ΠΏΠΎΠ΄Ρ ΠΎΠ΄ ΠΏΠΎΠ·Π²ΠΎΠ»ΡΠ΅Ρ ΠΏΠΎΠ»ΡΡΠ°ΡΡ Π²ΡΡΠΎΠΊΠΎΠΎΡΠΈΡΠ΅Π½Π½ΡΠ΅ ΠΏΡΠ΅ΠΏΠ°ΡΠ°ΡΡ ΠΈΠΌΠΌΡΠ½ΠΎΠ³Π»ΠΎΠ±ΡΠ»ΠΈΠ½ΠΎΠ², Π»ΠΈΡΠ΅Π½Π½ΡΠ΅ ΠΏΡΠΈΠΌΠ΅ΡΠ΅ΠΉ. ΠΡΠΎΠΌΠ΅ ΡΠΎΠ³ΠΎ, ΡΠ²ΠΎΠΉΡΡΠ²Π° ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ Π°Π½ΡΠΈΡΠ΅Π» ΠΈ ΠΈΡ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΌΠΎΠ³ΡΡ Π±ΡΡΡ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½Ρ Ρ ΠΏΠΎΠΌΠΎΡΡΡ Π³Π΅Π½Π½ΠΎ-ΠΈΠ½ΠΆΠ΅Π½Π΅ΡΠ½ΡΡ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠ². ΠΠ»Ρ ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΡ ΡΠ²ΠΎΠΉΡΡΠ² ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ Π°Π½ΡΠΈΡΠ΅Π» ΠΈΡΠΏΠΎΠ»ΡΠ·ΡΡΡ ΡΠ°Π·Π»ΠΈΡΠ½ΡΠ΅ Π²ΠΈΠ΄Ρ ΠΌΡΡΠ°Π³Π΅Π½Π΅Π·Π°, ΡΠ°ΠΊΠΈΠ΅ ΠΊΠ°ΠΊ ΡΠΎΠ·Π΄Π°Π½ΠΈΠ΅ ΠΎΠ³ΡΠ°Π½ΠΈΡΠ΅Π½Π½ΠΎΠ³ΠΎ ΠΊΠΎΠ»ΠΈΡΠ΅ΡΡΠ²Π° ΠΌΡΡΠ°Π½ΡΠ½ΡΡ ΡΠΎΡΠΌ Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ Π°Π½Π°Π»ΠΈΠ·Π° ΡΡΡΡΠΊΡΡΡΡ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΊΡΠ° Π°Π½ΡΠΈΡΠ΅Π»ΠΎ: Π°Π½ΡΠΈΠ³Π΅Π½, Π»ΠΈΠ±ΠΎ ΡΠΎΠ·Π΄Π°Π½ΠΈΠ΅ Π±ΠΎΠ»ΡΡΠΈΡ Π±ΠΈΠ±Π»ΠΈΠΎΡΠ΅ΠΊ ΠΌΡΡΠ°Π½ΡΠ½ΡΡ ΡΠΎΡΠΌ, ΠΈΠ· ΠΊΠΎΡΠΎΡΡΡ Π² Ρ ΠΎΠ΄Π΅ Π΄Π°Π»ΡΠ½Π΅ΠΉΡΠ΅ΠΉ ΡΠ°Π±ΠΎΡΡ ΠΎΡΠ±ΠΈΡΠ°ΡΡ Π²Π°ΡΠΈΠ°Π½ΡΡ Ρ ΡΠ»ΡΡΡΠ΅Π½Π½ΡΠΌΠΈ ΡΠ²ΠΎΠΉΡΡΠ²Π°ΠΌΠΈ. Π ΡΠ°ΠΊΠΈΠΌ ΠΌΠΎΠ΄ΠΈΡΠΈΠΊΠ°ΡΠΈΡΠΌ ΠΌΠΎΠΆΠ½ΠΎ ΠΎΡΠ½Π΅ΡΡΠΈ ΠΏΠΎΠ²ΡΡΠ΅Π½ΠΈΠ΅ Π°ΡΡΠΈΠ½Π½ΠΎΡΡΠΈ, ΡΠ²Π΅Π»ΠΈΡΠ΅Π½ΠΈΠ΅ ΡΠΈΡΠ»Π° Π°Π½ΡΠΈΠ³Π΅Π½-ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΠΈΡ ΡΡΠ°ΡΡΠΊΠΎΠ², ΠΈΠ·ΠΌΠ΅Π½Π΅Π½ΠΈΠ΅ ΡΠΎΡΡΠ°Π²Π° Π΄ΠΎΠΌΠ΅Π½ΠΎΠ², ΠΏΡΠΎΡΡΡΠ°Π½ΡΡΠ²Π΅Π½Π½ΠΎΠΉ ΠΎΡΠΈΠ΅Π½ΡΠ°ΡΠΈΠΈ ΡΡΠ°ΡΡΠΊΠΎΠ² ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΡ Ρ Π°Π½ΡΠΈΠ³Π΅Π½ΠΎΠΌ, ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎΠ³ΠΎ Π²Π΅ΡΠ°, ΠΈΠ·ΠΎΡΠ»Π΅ΠΊΡΡΠΈΡΠ΅ΡΠΊΠΎΠΉ ΡΠΎΡΠΊΠΈ ΠΈ ΠΏΠΎΡΠ΅Π½ΡΠΈΠ°Π»ΡΠ½ΠΎΠΉ ΠΈΠΌΠΌΡΠ½ΠΎΠ³Π΅Π½Π½ΠΎΡΡΠΈ. ΠΡΠ΅ ΠΎΠ΄Π½ΠΈΠΌ ΠΏΡΠ΅ΠΈΠΌΡΡΠ΅ΡΡΠ²ΠΎΠΌ Π³Π΅Π½Π½ΠΎ-ΠΈΠ½ΠΆΠ΅Π½Π΅ΡΠ½ΡΡ ΡΠ΅Ρ Π½ΠΎΠ»ΠΎΠ³ΠΈΠΉ ΡΠ²Π»ΡΠ΅ΡΡΡ Π²ΠΎΠ·ΠΌΠΎΠΆΠ½ΠΎΡΡΡ ΡΠΎΠ·Π΄Π°Π½ΠΈΡ ΡΠ°Π·Π½ΠΎΠΎΠ±ΡΠ°Π·Π½ΡΡ ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² Π°Π½ΡΠΈΡΠ΅Π», ΠΊΠΎΡΠΎΡΡΠ΅ ΠΌΠ΅Π½Π΅Π΅ ΠΈΠΌΠΌΡΠ½ΠΎΠ³Π΅Π½Π½Ρ ΠΈ ΠΌΠΎΠ³ΡΡ Π»Π΅Π³ΡΠ΅ ΠΏΡΠΎΠ½ΠΈΠΊΠ°ΡΡ Π² ΡΠΊΠ°Π½ΠΈ, ΡΠ΅ΠΌ ΠΏΠΎΠ»Π½ΠΎΡΠ°Π·ΠΌΠ΅ΡΠ½ΡΠ΅ ΠΌΠΎΠ»Π΅ΠΊΡΠ»Ρ ΠΈΠΌΠΌΡΠ½ΠΎΠ³Π»ΠΎΠ±ΡΠ»ΠΈΠ½ΠΎΠ². ΠΡΠΈ ΠΏΡΠ΅ΠΈΠΌΡΡΠ΅ΡΡΠ²Π° ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎ Π²Π°ΠΆΠ½Ρ Π΄Π»Ρ ΡΠΎΠ·Π΄Π°Π½ΠΈΡ ΡΠ΅ΡΠ°ΠΏΠ΅Π²ΡΠΈΡΠ΅ΡΠΊΠΈΡ Π°Π½ΡΠΈΡΠ΅Π» ΠΈ ΠΈΡ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ².
Π Π΄Π°Π½Π½ΠΎΠΉ ΡΠ°Π±ΠΎΡΠ΅ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΎ ΡΡΠ°Π²Π½Π΅Π½ΠΈΠ΅ ΡΠ²ΠΎΠΉΡΡΠ² ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘7 ΡΠΎ ΡΠ²ΠΎΠΉΡΡΠ²Π°ΠΌΠΈ ΠΈΡΡ ΠΎΠ΄Π½ΠΎΠ³ΠΎ ΠΏΠΎΠ»Π½ΠΎΡΠ°Π·ΠΌΠ΅ΡΠ½ΠΎΠ³ΠΎ Π°Π½ΡΠΈΡΠ΅Π»Π°. Π’Π°ΠΊΠΆΠ΅, Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² Π±ΡΠ»ΠΈ ΡΠΎΠ·Π΄Π°Π½Ρ ΡΠ°Π·Π»ΠΈΡΠ½ΡΠ΅ ΠΌΡΡΠ°Π½ΡΠ½ΡΠ΅ ΡΠΎΡΠΌΡ Ρ ΡΠ΅Π»ΡΡ ΡΠ²Π΅Π»ΠΈΡΠ΅Π½ΠΈΡ Π°ΡΡΠΈΠ½Π½ΠΎΡΡΠΈ ΠΈΡ Π²Π·Π°ΠΈΠΌΠΎΠ΄Π΅ΠΉΡΡΠ²ΠΈΡ Ρ Π°Π½ΡΠΈΠ³Π΅Π½ΠΎΠΌ. ΠΠ»Ρ Π°Π½Π°Π»ΠΈΠ·Π° Π²Π»ΠΈΡΠ½ΠΈΡ ΠΎΡΠ΄Π΅Π»ΡΠ½ΡΡ ΠΌΡΡΠ°ΡΠΈΠΉ Π½Π° Π°ΡΡΠΈΠ½Π½ΠΎΡΡΡ ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ Π°Π½ΡΠΈΡΠ΅Π» Π±ΡΠ» ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ ΡΡΠ°Π²Π½ΠΈΡΠ΅Π»ΡΠ½ΡΠΉ Π°Π½Π°Π»ΠΈΠ· ΠΈΠΌΠΌΡΠ½ΠΎΡ ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΡ ΡΠ²ΠΎΠΉΡΡΠ² ΠΏΠΎΠ»ΡΡΠ΅Π½Π½ΡΡ ΠΌΡΡΠ°Π½ΡΠ½ΡΡ ΡΠΎΡΠΌ.
ΠΠ±Π·ΠΎΡ Π»ΠΈΡΠ΅ΡΠ°ΡΡΡΡ.
ΠΡΠ²ΠΎΠ΄Ρ.
1. ΠΠΏΡΠ΅Π΄Π΅Π»Π΅Π½Π° Π½ΡΠΊΠ»Π΅ΠΎΡΠΈΠ΄Π½Π°Ρ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΡ ΠΠΡ 19Π‘7, ΠΊΠΎΠ΄ΠΈΡΡΡΡΠ°Ρ ΠΠ¦ ΠΈ ΡΠ’Π¦. ΠΡΠ»ΠΈ ΡΠΎΠ·Π΄Π°Π½Ρ ΠΌΠΎΠ»Π΅ΠΊΡΠ»ΡΡΠ½ΠΎ-Π³Π΅Π½Π΅ΡΠΈΡΠ΅ΡΠΊΠΈΠ΅ ΠΊΠΎΠ½ΡΡΡΡΠΊΡΠΈΠΈ Π΄Π»Ρ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ scFv ΠΈ Fab-ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² Π°Π½ΡΠΈΡΠ΅Π»Π°, ΠΏΠΎΠ΄ΠΎΠ±ΡΠ°Π½Ρ ΡΡΠ»ΠΎΠ²ΠΈΡ Π΄Π»Ρ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΠΈ ΠΈ ΠΎΡΠΈΡΡΠΊΠΈ ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΡ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ².
2. ΠΠΎΠΊΠ°Π·Π°Π½ΠΎ, ΡΡΠΎ ΡΠ΅ΠΊΠΎΠΌΠ±ΠΈΠ½Π°Π½ΡΠ½ΡΠ΅ ΡΡΠ°Π³ΠΌΠ΅Π½ΡΡ ΠΠΡ 19Π‘7 ΠΈ ΠΈΡΡ ΠΎΠ΄Π½ΠΎΠ΅ Π°Π½ΡΠΈΡΠ΅Π»ΠΎ ΠΎΠ±Π»Π°Π΄Π°ΡΡ Π°Π½Π°Π»ΠΎΠ³ΠΈΡΠ½ΡΠΌΠΈ ΠΈΠΌΠΌΡΠ½ΠΎΡ ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈΠΌΠΈ ΡΠ²ΠΎΠΉΡΡΠ²Π°ΠΌΠΈ ΠΈ ΠΏΠ°ΡΠ°ΠΌΠ΅ΡΡΠ°ΠΌΠΈ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΡ ΠΊΠ°ΠΊ Ρ ΠΎΡΠΈΡΠ΅Π½Π½ΡΠΌ hcTnl, ΡΠ°ΠΊ ΠΈ Ρ hcTnl Π² ΠΊΡΠΎΠ²ΠΈ ΡΠ΅Π»ΠΎΠ²Π΅ΠΊΠ°.
3. ΠΡΠΎΠ²Π΅Π΄Π΅Π½ΠΎ in silico ΠΌΠΎΠ΄Π΅Π»ΠΈΡΠΎΠ²Π°Π½ΠΈΠ΅ Π²ΡΠ΅Ρ Π²ΠΈΠ΄ΠΎΠ² ΠΌΡΡΠ°Π½ΡΠ½ΡΡ scFv-ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘7 Ρ ΠΎΠ΄ΠΈΠ½ΠΎΡΠ½ΡΠΌΠΈ ΠΈ ΠΈΠ·Π±ΡΠ°Π½Π½ΡΠΌΠΈ Π΄Π²ΠΎΠΉΠ½ΡΠΌΠΈ ΠΌΡΡΠ°ΡΠΈΡΠΌΠΈ Π² Π°Π½ΡΠΈΠ³Π΅Π½-ΡΠ²ΡΠ·ΡΠ²Π°ΡΡΠΈΡ ΡΡΠ°ΡΡΠΊΠ°Ρ , ΠΈ Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ ΠΌΠΎΠ΄Π΅Π»Π΅ΠΉ ΡΠ°ΡΡΡΠΈΡΠ°Π½Π° ΡΠ½Π΅ΡΠ³ΠΈΡ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΡ ΡΡΠΈΡ ΠΌΡΡΠ°Π½ΡΠ½ΡΡ ΡΠΎΡΠΌ Ρ Π°Π½ΡΠΈΠ³Π΅Π½ΠΎΠΌ.
4. ΠΠ· Π΄Π΅ΡΡΡΠΈ ΠΌΡΡΠ°Π½ΡΠ½ΡΡ ΡΠΎΡΠΌ scFv-ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘7, Π΄Π»Ρ ΠΊΠΎΡΠΎΡΡΡ Π±ΡΠ»Π° ΠΏΡΠ΅Π΄ΡΠΊΠ°Π·Π°Π½Π° in silico ΡΠ²Π΅Π»ΠΈΡΠ΅Π½Π½Π°Ρ Π°ΡΡΠΈΠ½Π½ΠΎΡΡΡ, ΡΠ΄Π°Π»ΠΎΡΡ ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡΠΎΠ²Π°ΡΡ ΡΠ΅ΡΡΡΠ΅ ΠΈΠΌΠΌΡΠ½ΠΎΡ ΠΈΠΌΠΈΡΠ΅ΡΠΊΠΈ Π°ΠΊΡΠΈΠ²Π½ΡΠ΅ ΡΠΎΡΠΌΡ. ΠΠΈ ΠΎΠ΄Π½Π° ΠΈΠ· ΡΡΠΈΡ ΠΌΡΡΠ°Π½ΡΠ½ΡΡ ΡΠΎΡΠΌ Π½Π΅ ΠΈΠΌΠ΅Π»Π° Π°ΡΡΠΈΠ½Π½ΠΎΡΡΡ Π²ΡΡΠ΅, ΡΠ΅ΠΌ Ρ Π΄ΠΈΠΊΠΎΠ³ΠΎ ΡΠΈΠΏΠ°.
5. Π‘ΠΎΠ·Π΄Π°Π½Π° Π±ΠΈΠ±Π»ΠΈΠΎΡΠ΅ΠΊΠ° ΡΠ°Π³ΠΎΠ²ΡΡ ΡΠ°ΡΡΠΈΡ, Π½Π΅ΡΡΡΠΈΡ Π½Π° ΡΠ²ΠΎΠ΅ΠΉ ΠΏΠΎΠ²Π΅ΡΡ Π½ΠΎΡΡΠΈ scFv-ΡΡΠ°Π³ΠΌΠ΅Π½ΡΡ, ΡΠΎΠ΄Π΅ΡΠΆΠ°ΡΠΈΠ΅ ΠΌΡΡΠ°ΡΠΈΠΈ Π² ΠΎΠ±Π»Π°ΡΡΠΈ CDR-H3, ΠΈ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ ΠΎΡΠ±ΠΎΡ ΡΠ°Π³ΠΎΠ²ΡΡ ΡΠ°ΡΡΠΈΡ Π½Π° ΠΎΡΠ½ΠΎΠ²Π΅ ΠΈΡ ΡΠΏΠΎΡΠΎΠ±Π½ΠΎΡΡΠΈ ΠΊ ΡΠ²ΡΠ·ΡΠ²Π°Π½ΠΈΡ Π°Π½ΡΠΈΠ³Π΅Π½Π°. ΠΠ°ΠΉΠ΄Π΅Π½Ρ Π°ΠΌΠΈΠ½ΠΎΠΊΠΈΡΠ»ΠΎΡΠ½ΡΠ΅ ΠΏΠΎΠ·ΠΈΡΠΈΠΈ Π² CDR-H3 ΠΠΡ 19Π‘7 (Π97, Π102, Π100, Π101, Π98) ΠΈ ΠΊΠΎΠ½ΠΊΡΠ΅ΡΠ½ΡΠ΅ ΠΌΡΡΠ°ΡΠΈΠΈ (YH97 °F, YH97Q, AH100N, YH102V, YH102D), ΠΊΠΎΡΠΎΡΡΠ΅ Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ ΠΏΡΠ΅Π΄ΡΡΠ°Π²Π»Π΅Π½Ρ ΡΡΠ΅Π΄ΠΈ ΠΎΡΠΎΠ±ΡΠ°Π½Π½ΡΡ Π²Π°ΡΠΈΠ°Π½ΡΠΎΠ².
6. ΠΡΠ»Π° ΠΎΡΡΡΠ΅ΡΡΠ²Π»Π΅Π½Π° ΡΠΊΡΠΏΡΠ΅ΡΡΠΈΡ Π²ΠΎΡΡΠΌΠΈ ΠΌΡΡΠ°Π½ΡΠ½ΡΡ Π²Π°ΡΠΈΠ°Π½ΡΠΎΠ² scFv-ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠΎΠ² ΠΠΡ 19Π‘7, ΠΎΡΠΎΠ±ΡΠ°Π½Π½ΡΡ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΡΠ°Π³ΠΎΠ²ΠΎΠ³ΠΎ Π΄ΠΈΡΠΏΠ»Π΅Ρ. ΠΠ²Π° ΠΈΠ· Π½ΠΈΡ (YH97 °F ΠΈ AH100N+YH97F) ΠΎΠ±Π»Π°Π΄Π°Π»ΠΈ ΡΠ²Π΅Π»ΠΈΡΠ΅Π½Π½ΠΎΠΉ Π°ΡΡΠΈΠ½Π½ΠΎΡΡΡΡ ΠΏΠΎ ΡΡΠ°Π²Π½Π΅Π½ΠΈΡ Ρ scFv-ΡΡΠ°Π³ΠΌΠ΅Π½ΡΠ°ΠΌΠΈ Π΄ΠΈΠΊΠΎΠ³ΠΎ ΡΠΈΠΏΠ°.
ΠΠ»Π°Π³ΠΎΠ΄Π°ΡΠ½ΠΎΡΡΠΈ.
ΠΠ²ΡΠΎΡ Π²ΡΡΠ°ΠΆΠ°Π΅Ρ Π³Π»ΡΠ±ΠΎΠΊΡΡ ΠΏΡΠΈΠ·Π½Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΡ ΡΠ²ΠΎΠ΅ΠΌΡ Π½Π°ΡΡΠ½ΠΎΠΌΡ ΡΡΠΊΠΎΠ²ΠΎΠ΄ΠΈΡΠ΅Π»Ρ, Π΄ΠΎΠΊΡΠΎΡΡ Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡΠ΅ΡΠΊΠΈΡ Π½Π°ΡΠΊ, ΠΠ°ΡΡΡΡ Π΅ Π. Π. Π·Π° ΡΡΡΠΊΠΎΠ΅ ΡΡΠΊΠΎΠ²ΠΎΠ΄ΡΡΠ²ΠΎ, ΠΊΠΎΠ»Π»Π΅ΠΊΡΠΈΠ²Ρ Π»Π°Π±ΠΎΡΠ°ΡΠΎΡΠΈΠΈ ΠΈ ΠΊΠ°ΡΠ΅Π΄ΡΡ Π·Π° Π½Π΅ΠΎΡΠ΅Π½ΠΈΠΌΡΡ ΠΏΠΎΠΌΠΎΡΡ Π² Π²ΡΠΏΠΎΠ»Π½Π΅Π½ΠΈΠΈ Π΄Π°Π½Π½ΠΎΠΉ ΠΈΡΡΠ»Π΅Π΄ΠΎΠ²Π°ΡΠ΅Π»ΡΡΠΊΠΎΠΉ ΡΠ°Π±ΠΎΡΡ ΠΈ, Π² ΠΎΡΠΎΠ±Π΅Π½Π½ΠΎΡΡΠΈ, Π‘Π΅ΡΠ΅Π±ΡΡΠ½ΠΎΠΉ Π. Π. ΠΈ ΠΠΎΡΡΠ½ΠΈΠΊΠΎΠ²Ρ Π. Π. Π·Π° ΠΏΠΎΠΌΠΎΡΡ ΠΈ ΡΡΠ°ΡΡΠΈΠ΅ Π² ΡΠ°Π±ΠΎΡΠ΅ Π½Π° Π²ΡΠ΅Ρ Π΅Π΅ ΡΡΠ°ΠΏΠ°Ρ .
Π’Π°ΠΊΠΆΠ΅ Π°Π²ΡΠΎΡ Π²ΡΡΠ°ΠΆΠ°Π΅Ρ ΡΠ²ΠΎΡ ΠΏΡΠΈΠ·Π½Π°ΡΠ΅Π»ΡΠ½ΠΎΡΡΡ ΠΠ°ΠΌΠ°Π½Ρ Π. Π. ΠΈ ΠΠΎΠΌΠ°ΠΊΠΈΠ½Ρ Π―. Π. Π·Π° ΠΌΠ½ΠΎΠ³ΠΎΡΠΈΡΠ»Π΅Π½Π½ΡΠ΅ ΠΊΠΎΠ½ΡΡΠ»ΡΡΠ°ΡΠΈΠΈ ΠΏΠΎ ΠΎΡΠ±ΠΎΡΡ ΠΌΠ΅ΡΠΎΠ΄ΠΎΠΌ ΡΠ°Π³ΠΎΠ²ΠΎΠ³ΠΎ Π΄ΠΈΡΠΏΠ»Π΅Ρ ΠΈ ΠΠ°Π·ΡΠΊΠΈΠ½Ρ Π. Π. Π·Π° ΠΏΠΎΠΌΠΎΡΡ ΠΏΡΠΈ ΠΏΡΠΎΠ²Π΅Π΄Π΅Π½ΠΈΠΈ Ρ 5/7/ΡΠΎ ΠΌΡΡΠ°Π³Π΅Π½Π΅Π·Π°.
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