Π”ΠΈΠΏΠ»ΠΎΠΌΡ‹, курсовыС, Ρ€Π΅Ρ„Π΅Ρ€Π°Ρ‚Ρ‹, ΠΊΠΎΠ½Ρ‚Ρ€ΠΎΠ»ΡŒΠ½Ρ‹Π΅...
Брочная ΠΏΠΎΠΌΠΎΡ‰ΡŒ Π² ΡƒΡ‡Ρ‘Π±Π΅

Π‘Ρ‚Ρ€ΡƒΠΊΡ‚ΡƒΡ€Π½ΠΎ-Ρ„ΡƒΠ½ΠΊΡ†ΠΈΠΎΠ½Π°Π»ΡŒΠ½ΠΎΠ΅ исслСдованиС Ρ…ΠΈΠΌΠ°Π·ΠΎΠΏΠΎΠ΄ΠΎΠ±Π½ΠΎΠΉ ΠΏΡ€ΠΎΡ‚Π΅Π°Π·Ρ‹ β€” Π½ΠΎΠ²ΠΎΠ³ΠΎ Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚Π° ΠΈΠ· Π΄ΡƒΠΎΠ΄Π΅Π½ΡƒΠΌΠ° Π±Ρ‹ΠΊΠ°

Π”ΠΈΡΡΠ΅Ρ€Ρ‚Π°Ρ†ΠΈΡΠŸΠΎΠΌΠΎΡ‰ΡŒ Π² Π½Π°ΠΏΠΈΡΠ°Π½ΠΈΠΈΠ£Π·Π½Π°Ρ‚ΡŒ ΡΡ‚ΠΎΠΈΠΌΠΎΡΡ‚ΡŒΠΌΠΎΠ΅ΠΉ Ρ€Π°Π±ΠΎΡ‚Ρ‹

ИсслСдовано ΠΈΠ½Π³ΠΈΠ±ΠΈΡ€ΡƒΡŽΡ‰Π΅Π΅ дСйствиС Π½Π° ΠΈΠ·ΡƒΡ‡Π°Π΅ΠΌΡƒΡŽ ΠΏΡ€ΠΎΡ‚Π΅Π°Π·Ρƒ ряда синтСтичСских ΠΈ Π±Π΅Π»ΠΊΠΎΠ²Ρ‹Ρ… ΠΈΠ½Π³ΠΈΠ±ΠΈΡ‚ΠΎΡ€ΠΎΠ² сСриновых ΠΏΡ€ΠΎΡ‚Π΅Π°Π·. УстановлСно, Ρ‡Ρ‚ΠΎ, ΠΏΠΎΠ΄ΠΎΠ±Π½ΠΎ Ρ…ΠΈΠΌΠ°Π·Π°ΠΌ, Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚ Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ эффСктивно ингибируСтся Π±Π΅Π»ΠΊΠΎΠ²Ρ‹ΠΌΠΈ ΠΈΠ½Π³ΠΈΠ±ΠΈΡ‚ΠΎΡ€Π°ΠΌΠΈ Ρ‚ΠΈΠΏΠ° ΠšΡƒΠ½ΠΈΡ‚Ρ†Π° ΠΈ Π‘Π°ΡƒΠΌΠ°Π½Π°-Π‘ΠΈΡ€ΠΊ ΠΈΠ· Π±ΠΎΠ±ΠΎΠ²Ρ‹Ρ…, Π½ΠΎ ΠΏΡ€ΠΎΡΠ²Π»ΡΠ΅Ρ‚ ΡƒΡΡ‚ΠΎΠΉΡ‡ΠΈΠ²ΠΎΡΡ‚ΡŒ ΠΊ Π΄Π΅ΠΉΡΡ‚Π²ΠΈΡŽ панкрСатичСского трипсинового ΠΈΠ½Π³ΠΈΠ±ΠΈΡ‚ΠΎΡ€Π° BPTI. Из ΡΠ»ΠΈΠ·ΠΈΡΡ‚ΠΎΠΉ Π΄ΡƒΠΎΠ΄Π΅Π½ΡƒΠΌΠ° Π±Ρ‹ΠΊΠ° с ΠΈΡΠΏΠΎΠ»ΡŒΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ Π°Ρ„Ρ„ΠΈΠ½Π½ΠΎΠΉ… Π§ΠΈΡ‚Π°Ρ‚ΡŒ Π΅Ρ‰Ρ‘ >

Π‘ΠΎΠ΄Π΅Ρ€ΠΆΠ°Π½ΠΈΠ΅

  • I. Π‘Π ΠΠ’ΠΠ˜Π’Π•Π›Π¬ΠΠΠ― Π₯ΠΠ ΠΠšΠ’Π•Π Π˜Π‘Π’Π˜ΠšΠ Π”Π£ΠžΠ”Π•ΠΠΠ—Π« И Π₯Π˜ΠœΠΠ—, Π€Π•Π ΠœΠ•ΠΠ’ΠžΠ’, БВРУКВУРНО Π ΠžΠ”Π‘Π’Π’Π•ΠΠΠ«Π₯ Π₯Π˜ΠœΠΠ—ΠžΠŸΠžΠ”ΠžΠ‘ΠΠžΠ™ ΠŸΠ ΠžΠ’Π•ΠΠ—Π• (Π»ΠΈΡ‚Π΅Ρ€Π°Ρ‚ΡƒΡ€Π½Ρ‹ΠΉ ΠΎΠ±Π·ΠΎΡ€)
  • 1. Π”ΡƒΠΎΠ΄Π΅Π½Π°Π·Π°, сСриновая ΠΏΡ€ΠΎΡ‚Π΅Π°Π·Π° эпитСлиоцитов Π±Ρ€ΡƒΠ½Π½Π΅Ρ€ΠΎΠ²Ρ‹Ρ… ΠΆΠ΅Π»Π΅Π·
    • 1. 1. Локализация ΠΈ ΠΏΡ€Π΅Π΄ΠΏΠΎΠ»Π°Π³Π°Π΅ΠΌΠ°Ρ биологичСская Ρ€ΠΎΠ»ΡŒ Π΄ΡƒΠΎΠ΄Π΅Π½Π°Π·Ρ‹
    • 1. 2. ΠœΠΎΠ»Π΅ΠΊΡƒΠ»ΡΡ€Π½Ρ‹Π΅ свойства ΠΈ ΡΡ‚Ρ€ΡƒΠΊΡ‚ΡƒΡ€Π° Π΄ΡƒΠΎΠ΄Π΅Π½Π°Π·Ρ‹
    • 1. 3. ЭнзиматичСскиС свойства Π΄ΡƒΠΎΠ΄Π΅Π½Π°Π·Ρ‹
  • 2. Π₯ΠΈΠΌΠ°Π·Ρ‹ Ρ‚ΡƒΡ‡Π½Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΎΠΊ
    • 2. 1. Π“Π΅Ρ‚Π΅Ρ€ΠΎΠ³Π΅Π½Π½ΠΎΡΡ‚ΡŒ ΠΈ Π±ΠΈΠΎΠ»ΠΎΠ³ΠΈΡ‡Π΅ΡΠΊΠ°Ρ Π·Π½Π°Ρ‡ΠΈΠΌΠΎΡΡ‚ΡŒ Ρ‚ΡƒΡ‡Π½Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΎΠΊ
    • 2. 2. ВканСвая локализация ΠΈ ΠΌΠΎΠ»Π΅ΠΊΡƒΠ»ΡΡ€Π½Ρ‹Π΅ свойства Ρ…ΠΈΠΌΠ°Π·
    • 2. 3. Π‘Ρ‚Ρ€ΡƒΠΊΡ‚ΡƒΡ€Π½Ρ‹Π΅ особСнности Ρ…ΠΈΠΌΠ°Π·
    • 2. 4. Π£ΠΏΠ°ΠΊΠΎΠ²ΠΊΠ° ΠΈ Ρ…Ρ€Π°Π½Π΅Π½ΠΈΠ΅ Ρ…ΠΈΠΌΠ°Π· Π² ΡΠ΅ΠΊΡ€Π΅Ρ‚ΠΎΡ€Π½Ρ‹Ρ… Π³Ρ€Π°Π½ΡƒΠ»Π°Ρ…
    • 2. 5. Активация ΠΏΡ€Π΅Π΄ΡˆΠ΅ΡΡ‚Π²Π΅Π½Π½ΠΈΠΊΠΎΠ² Ρ…ΠΈΠΌΠ°Π·
    • 2. 6. Бубстратная ΡΠΏΠ΅Ρ†ΠΈΡ„ΠΈΡ‡Π½ΠΎΡΡ‚ΡŒ Ρ…ΠΈΠΌΠ°Π·
      • 2. 6. 1. БинтСтичСскиС субстраты
      • 2. 6. 2. ΠŸΠΎΠ»ΠΈΠΏΠ΅ΠΏΡ‚ΠΈΠ΄Π½Ρ‹Π΅ ΠΈ Π±Π΅Π»ΠΊΠΎΠ²Ρ‹Π΅ субстраты
    • 2. 7. Π˜Π½Π³ΠΈΠ±ΠΈΡ‚ΠΎΡ€Ρ‹ Ρ…ΠΈΠΌΠ°Π·
      • 2. 7. 1. БинтСтичСскиС ΠΈΠ½Π³ΠΈΠ±ΠΈΡ‚ΠΎΡ€Ρ‹
      • 2. 7. 2. ΠŸΡ€ΠΈΡ€ΠΎΠ΄Π½Ρ‹Π΅ ΠΈΠ½Π³ΠΈΠ±ΠΈΡ‚ΠΎΡ€Ρ‹ Ρ…ΠΈΠΌΠ°Π·
    • 2. 8. ЀизиологичСская Ρ€ΠΎΠ»ΡŒ Ρ…ΠΈΠΌΠ°Π·
  • II. РЕЗУЛЬВАВЫ И ΠžΠ‘Π‘Π£Π–Π”Π•ΠΠ˜Π•
  • 1. ΠžΡ‡ΠΈΡΡ‚ΠΊΠ° Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚Π°
  • 2. ΠšΡ€ΠΈΡ‚Π΅Ρ€ΠΈΠΈ чистоты ΠΈ ΠΌΠΎΠ»Π΅ΠΊΡƒΠ»ΡΡ€Π½Ρ‹Π΅ свойства Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚Π°
  • 3. Π‘Ρ‚Π°Π±ΠΈΠ»ΡŒΠ½ΠΎΡΡ‚ΡŒ Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚Π°
  • 4. N-концСвая ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°Ρ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚ΡŒ ChIP
  • 5. ВлияниС рН, Ρ‚Π΅ΠΌΠΏΠ΅Ρ€Π°Ρ‚ΡƒΡ€Ρ‹ ΠΈ ΠΈΠΎΠ½Π½ΠΎΠΉ силы Π½Π° Π°ΠΊΡ‚ΠΈΠ²Π½ΠΎΡΡ‚ΡŒ Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚Π°
  • 6. Бубстратная ΡΠΏΠ΅Ρ†ΠΈΡ„ΠΈΡ‡Π½ΠΎΡΡ‚ΡŒ ChIP
    • 6. 1. БинтСтичСскиС субстраты
    • 6. 2. ΠŸΡ€ΠΈΡ€ΠΎΠ΄Π½Ρ‹Π΅ ΠΏΠΎΠ»ΠΈΠΏΠ΅ΠΏΡ‚ΠΈΠ΄Π½Ρ‹Π΅ субстраты
  • 7. Π˜Π½Π³ΠΈΠ±ΠΈΡ‚ΠΎΡ€Π½Ρ‹ΠΉ Π°Π½Π°Π»ΠΈΠ·
  • 8. Π˜ΠΌΠΌΡƒΠ½Π½ΠΎΠ³ΠΈΡΡ‚ΠΎΡ…ΠΈΠΌΠΈΡ‡Π΅ΡΠΊΠ°Ρ локализация ChIP
  • III. Π­ΠšΠ‘ΠŸΠ•Π Π˜ΠœΠ•ΠΠ’ΠΠ›Π¬ΠΠΠ― ЧАБВ
  • 1. ΠœΠ°Ρ‚Π΅Ρ€ΠΈΠ°Π»Ρ‹
  • 2. ΠœΠ΅Ρ‚ΠΎΠ΄Ρ‹
    • 2. 1. ΠžΡ‡ΠΈΡΡ‚ΠΊΠ° Ρ…ΠΈΠΌΠ°Π·ΠΎΠΏΠΎΠ΄ΠΎΠ±Π½ΠΎΠΉ Π»Ρ€ΠΎΡ‚Π΅Π°Π·Ρ‹
    • 2. 2. ΠžΠΏΡ€Π΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ Π±Π΅Π»ΠΊΠ°
    • 2. 3. ΠžΠΏΡ€Π΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ активности
    • 2. 4. ΠžΠΏΡ€Π΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ ΠΊΠΎΠ½Ρ†Π΅Π½Ρ‚Ρ€Π°Ρ†ΠΈΠΈ Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚Π°
    • 2. 5. ΠžΠΏΡ€Π΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ кинСтичСских ΠΏΠ°Ρ€Π°ΠΌΠ΅Ρ‚Ρ€ΠΎΠ² Π³ΠΈΠ΄Ρ€ΠΎΠ»ΠΈΠ·Π° субстратов
    • 2. 6. Π“ΠΈΠ΄Ρ€ΠΎΠ»ΠΈΠ· Π±Π΅Π»ΠΊΠΎΠ² ΠΈ ΠΏΠ΅ΠΏΡ‚ΠΈΠ΄ΠΎΠ² ChIP
    • 2. 7. Масс-спСктромСтричСский Π°Π½Π°Π»ΠΈΠ·
    • 2. 8. Π“Π΅Π»ΡŒ-элСктрофорСз
    • 2. 9. АналитичСскиС ΠΌΠ΅Ρ‚ΠΎΠ΄Ρ‹ опрСдСлСния ChIP
    • 2. 10. ΠžΠΏΡ€Π΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ рН-зависимости ChIP
    • 2. 11. Π˜Π½Π³ΠΈΠ±ΠΈΡ€ΠΎΠ²Π°Π½ΠΈΠ΅ ChIP
    • 2. 12. ΠžΠΏΡ€Π΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ N-ΠΊΠΎΠ½Ρ†Π΅Π²ΠΎΠΉ ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°Ρ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚ΠΈ Π±Π΅Π»ΠΊΠ°
    • 2. 13. ΠŸΠΎΠ»ΡƒΡ‡Π΅Π½ΠΈΠ΅ Π°Π½Ρ‚ΠΈΡ‚Π΅Π» ΠΊ ChIP
    • 2. 14. Π˜ΠΌΠΌΡƒΠ½ΠΎΠ³ΠΈΡΡ‚ΠΎΡ…ΠΈΠΌΠΈΡ‡Π΅ΡΠΊΠΈΠΉ Π°Π½Π°Π»ΠΈΠ·
  • Π’Π«Π’ΠžΠ”Π«

Π‘Ρ‚Ρ€ΡƒΠΊΡ‚ΡƒΡ€Π½ΠΎ-Ρ„ΡƒΠ½ΠΊΡ†ΠΈΠΎΠ½Π°Π»ΡŒΠ½ΠΎΠ΅ исслСдованиС Ρ…ΠΈΠΌΠ°Π·ΠΎΠΏΠΎΠ΄ΠΎΠ±Π½ΠΎΠΉ ΠΏΡ€ΠΎΡ‚Π΅Π°Π·Ρ‹ β€” Π½ΠΎΠ²ΠΎΠ³ΠΎ Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚Π° ΠΈΠ· Π΄ΡƒΠΎΠ΄Π΅Π½ΡƒΠΌΠ° Π±Ρ‹ΠΊΠ° (Ρ€Π΅Ρ„Π΅Ρ€Π°Ρ‚, курсовая, Π΄ΠΈΠΏΠ»ΠΎΠΌ, ΠΊΠΎΠ½Ρ‚Ρ€ΠΎΠ»ΡŒΠ½Π°Ρ)

ΠŸΡ€ΠΎΡ‚Π΅ΠΎΠ»ΠΈΡ‚ΠΈΡ‡Π΅ΡΠΊΠΈΠ΅ Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚Ρ‹ (ΠΏΡ€ΠΎΡ‚Π΅Π°Π·Ρ‹), Π² Ρ‚ΠΎΠΌ числС сСриновыС ΠΏΡ€ΠΎΡ‚Π΅Π°Π·Ρ‹, ΠΈΠ³Ρ€Π°ΡŽΡ‚ Π²Π°ΠΆΠ½ΡƒΡŽ Ρ€ΠΎΠ»ΡŒ Π² Ρ€Π΅Π³ΡƒΠ»ΡΡ†ΠΈΠΈ ΠΌΠ½ΠΎΠ³ΠΎΠΎΠ±Ρ€Π°Π·Π½Ρ‹Ρ… биологичСских процСссов всСх ΠΆΠΈΠ²Ρ‹Ρ… ΠΎΡ€Π³Π°Π½ΠΈΠ·ΠΌΠΎΠ², осущСствляя ΠΌΠΎΠ΄ΠΈΡ„ΠΈΠΊΠ°Ρ†ΠΈΡŽ биологичСски Π°ΠΊΡ‚ΠΈΠ²Π½Ρ‹Ρ… Π±Π΅Π»ΠΊΠΎΠ² ΠΈ ΠΏΠ΅ΠΏΡ‚ΠΈΠ΄ΠΎΠ² ΠΈ Ρ‚Π΅ΠΌ самым опрСдСляя Π½Π°Ρ‡Π°Π»ΠΎ ΠΈΠ»ΠΈ ΠΏΡ€Π΅ΠΊΡ€Π°Ρ‰Π΅Π½ΠΈΠ΅ физиологичСских процСссов.

Π‘Π΅Ρ€ΠΈΠ½ΠΎΠ²Ρ‹Π΅ ΠΏΡ€ΠΎΡ‚Π΅Π°Π·Ρ‹ ΡˆΠΈΡ€ΠΎΠΊΠΎ распространСны Π² ΠΏΡ€ΠΈΡ€ΠΎΠ΄Π΅ ΠΈ ΠΏΡ€ΠΈΡΡƒΡ‚ΡΡ‚Π²ΡƒΡŽΡ‚ ΠΊΠ°ΠΊ Π² ΠΌΠΈΠΊΡ€ΠΎΠΎΡ€Π³Π°Π½ΠΈΠ·ΠΌΠ°Ρ…, Ρ‚Π°ΠΊ ΠΈ Π² Π²Ρ‹ΡΡˆΠΈΡ… растСниях ΠΈ ΠΆΠΈΠ²ΠΎΡ‚Π½Ρ‹Ρ…, Π²ΠΊΠ»ΡŽΡ‡Π°Ρ Ρ‡Π΅Π»ΠΎΠ²Π΅ΠΊΠ°.

ВсС сСриновыС ΠΏΡ€ΠΎΡ‚Π΅Π°Π·Ρ‹ Π½Π° ΠΎΡΠ½ΠΎΠ²Π°Π½ΠΈΠΈ Π΄Π°Π½Π½Ρ‹Ρ… ΠΎΠ± ΠΈΡ… ΠΏΡ€ΠΎΡΡ‚ранствСнном строСнии Ρ€Π°Π·Π΄Π΅Π»ΡΡŽΡ‚ Π½Π° Ρ‚Ρ€ΠΈ сСмСйства: химотрипсина, субтилизина ΠΈ ΠΊΠ°Ρ€Π±ΠΎΠΊΡΠΈΠΏΠ΅ΠΏΡ‚ΠΈΠ΄Π°Π·Ρ‹ II. ΠŸΡ€Π΅Π΄ΡΡ‚Π°Π²ΠΈΡ‚Π΅Π»ΠΈ этих сСмСйств Π±Π΅Ρ€ΡƒΡ‚ Π½Π°Ρ‡Π°Π»ΠΎ ΠΎΡ‚ Ρ€Π°Π·Π½Ρ‹Ρ… ΡΠ²ΠΎΠ»ΡŽΡ†ΠΈΠΎΠ½Π½Ρ‹Ρ… ΠΏΡ€Π΅Π΄ΡˆΠ΅ΡΡ‚Π²Π΅Π½Π½ΠΈΠΊΠΎΠ² ΠΈ ΠΎΡ‚Π»ΠΈΡ‡Π°ΡŽΡ‚ΡΡ Π΄Ρ€ΡƒΠ³ ΠΎΡ‚ Π΄Ρ€ΡƒΠ³Π° ΠΏΠΎ ΠΏΠ΅Ρ€Π²ΠΈΡ‡Π½ΠΎΠΉ структурС ΠΈ ΠΏΡ€ΠΎΡΡ‚ранствСнной ΡƒΠΊΠ»Π°Π΄ΠΊΠ΅ ΠΏΠΎΠ»ΠΈΠΏΠ΅ΠΏΡ‚ΠΈΠ΄Π½Ρ‹Ρ… Ρ†Π΅ΠΏΠ΅ΠΉ. Однако, всС сСриновыС ΠΏΡ€ΠΎΡ‚Π΅Π°Π·Ρ‹ Ρ€Π°Π·Π½Ρ‹ΠΌΠΈ ΡΠ²ΠΎΠ»ΡŽΡ†ΠΈΠΎΠ½Π½Ρ‹ΠΌΠΈ путями ΠΏΡ€ΠΈΡˆΠ»ΠΈ ΠΊ ΠΎΠ΄ΠΈΠ½Π°ΠΊΠΎΠ²ΠΎΠΌΡƒ каталитичСскому ΠΌΠ΅Ρ…Π°Π½ΠΈΠ·ΠΌΡƒ ΠΈ ΡΠΎΠ΄Π΅Ρ€ΠΆΠ°Ρ‚ Π² Π°ΠΊΡ‚ΠΈΠ²Π½ΠΎΠΌ Ρ†Π΅Π½Ρ‚Ρ€Π΅ ΠΌΠΎΠ»Π΅ΠΊΡƒΠ»Ρ‹ каталитичСски Π°ΠΊΡ‚ΠΈΠ²Π½Ρ‹Π΅ остатки His, Ser ΠΈ Asp Π² ΠΈΠ΄Π΅Π½Ρ‚ΠΈΡ‡Π½ΠΎΠΉ гСомСтричСской ΠΎΡ€ΠΈΠ΅Π½Ρ‚Π°Ρ†ΠΈΠΈ.

БСмСйство химотрипсина Π²ΠΊΠ»ΡŽΡ‡Π°Π΅Ρ‚ большоС число ΠΏΡ€ΠΎΡ‚Π΅Π°Π· ΠΈΠ· Π±Π°ΠΊΡ‚Π΅Ρ€ΠΈΠ°Π»ΡŒΠ½Ρ‹Ρ… ΠΈ Π²Ρ‹ΡΡˆΠΈΡ… ΠΎΡ€Π³Π°Π½ΠΈΠ·ΠΌΠΎΠ² ΠΈ ΠΏΡ€ΠΈΠ²Π»Π΅ΠΊΠ°Π΅Ρ‚ большой интСрСс исслСдоватСлСй. Π’ ΠΎΡ€Π³Π°Π½ΠΈΠ·ΠΌΠ΅ ΠΎΠ½ΠΈ Π²Ρ‹ΠΏΠΎΠ»Π½ΡΡŽΡ‚ ΠΊΠ°ΠΊ Π΄Π΅ΡΡ‚Ρ€ΡƒΠΊΡ‚ΠΈΠ²Π½ΡƒΡŽ, Ρ‚Π°ΠΊ ΠΈ Ρ€Π΅Π³ΡƒΠ»ΡΡ‚ΠΎΡ€Π½ΡƒΡŽ Ρ„ΡƒΠ½ΠΊΡ†ΠΈΠΈ: Π³ΠΈΠ΄Ρ€ΠΎΠ»ΠΈΠ· Π±Π΅Π»ΠΊΠΎΠ²Ρ‹Ρ… ΠΊΠΎΠΌΠΏΠΎΠ½Π΅Π½Ρ‚ΠΎΠ² ΠΏΠΈΡ‰ΠΈ (Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚Ρ‹ ΠΏΠΎΠ΄ΠΆΠ΅Π»ΡƒΠ΄ΠΎΡ‡Π½ΠΎΠΉ ΠΆΠ΅Π»Π΅Π·Ρ‹ трипсин, химотрипсин, эластаза,) — посттрансляционный процСссинг Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚ΠΎΠ², Π³ΠΎΡ€ΠΌΠΎΠ½ΠΎΠ², Ρ†ΠΈΡ‚ΠΎΠΊΠΈΠ½ΠΎΠ² (энтСропСптидаза, ΠΊΠ°Π»Π»ΠΈΠΊΡ€Π΅ΠΈΠ½, трипсин, Π³Ρ€Π°Π½Π·ΠΈΠΌ Π’) — участиС Π² ΠΊΠ°ΡΠΊΠ°Π΄Π½Ρ‹Ρ… рСакциях Π°ΠΊΡ‚ΠΈΠ²Π°Ρ†ΠΈΠΈ Π·ΠΈΠΌΠΎΠ³Π΅Π½ΠΎΠ² Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚ΠΎΠ², ΠΊΠΎΠ½Ρ‚Ρ€ΠΎΠ»ΠΈΡ€ΡƒΡŽΡ‰ΠΈΡ… процСсс свСртывания ΠΊΡ€ΠΎΠ²ΠΈ ΠΈ Ρ„ΠΈΠ±Ρ€ΠΈΠ½ΠΎΠ»ΠΈΠ·Π° (ΠΏΠ»Π°Π·ΠΌΠΈΠ½, Ρ‚Ρ€ΠΎΠΌΠ±ΠΈΠ½, Ρ„Π°ΠΊΡ‚ΠΎΡ€Ρ‹ Va, Vila, Villa, 1Π₯Π°, Π₯Π° ΠΈ Π΄Ρ€.) ΠΈ ΡΠΈΡΡ‚Π΅ΠΌΡ‹ ΠΊΠΎΠΌΠΏΠ»Π΅ΠΌΠ΅Π½Ρ‚Π° (Ρ„Π°ΠΊΡ‚ΠΎΡ€Ρ‹ Π‘1Π³, C1s, I, D). ΠšΡ€ΠΎΠΌΠ΅ Ρ‚ΠΎΠ³ΠΎ, сСриновыС ΠΏΡ€ΠΎΡ‚Π΅Π°Π·Ρ‹ этого сСмСйства ΠΈΠ³Ρ€Π°ΡŽΡ‚ ΡΡƒΡ‰Π΅ΡΡ‚Π²Π΅Π½Π½ΡƒΡŽ Ρ€ΠΎΠ»ΡŒ Π² ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠΉ Π΄ΠΈΡ„Ρ„Π΅Ρ€Π΅Π½Ρ†ΠΈΠ°Ρ†ΠΈΠΈ ΠΈ ΠΏΡ€ΠΎΠ»ΠΈΡ„Π΅Ρ€Π°Ρ†ΠΈΠΈ.

Для ΠΌΠ½ΠΎΠ³ΠΈΡ… Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚ΠΎΠ² ΠΊ Π½Π°ΡΡ‚оящСму Π²Ρ€Π΅ΠΌΠ΅Π½ΠΈ Ρ…ΠΎΡ€ΠΎΡˆΠΎ извСстны энзиматичСскиС свойства ΠΈ Π²Ρ‹ΡΠ²Π»Π΅Π½Ρ‹ ΠΈΡ… ΠΏΡ€ΠΈΡ€ΠΎΠ΄Π½Ρ‹Π΅ субстраты. Однако, сущСствуСт ряд сСриновых ΠΏΡ€ΠΎΡ‚Π΅Π°Π· сСмСйства химотрипсина, ΠΈΠ·ΡƒΡ‡Π΅Π½ΠΈΠ΅ ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Ρ… Π½Π°Ρ‡Π°Π»ΠΎΡΡŒ ΡΡ€Π°Π²Π½ΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎ Π½Π΅Π΄Π°Π²Π½ΠΎ. К Ρ‡ΠΈΡΠ»Ρƒ Ρ‚Π°ΠΊΠΈΡ… Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚ΠΎΠ² относятся ΠΏΡ€ΠΎΡ‚Π΅Π°Π·Ρ‹ сСкрСторных Π³Ρ€Π°Π½ΡƒΠ» гСмопоэтичСских ΠΊΠ»Π΅Ρ‚ΠΎΠΊ ΠΌΠ»Π΅ΠΊΠΎΠΏΠΈΡ‚Π°ΡŽΡ‰ΠΈΡ…, ΠΎΠ±ΡŠΠ΅Π΄ΠΈΠ½Π΅Π½Π½Ρ‹Ρ… Π² Π³Ρ€ΡƒΠΏΠΏΡƒ Ρ‚Π°ΠΊ Π½Π°Π·Ρ‹Π²Π°Π΅ΠΌΡ‹Ρ… Π³Ρ€Π°Π½Π·ΠΈΠΌΠΎΠΏΠΎΠ΄ΠΎΠ±Π½Ρ‹Ρ… ΠΏΡ€ΠΎΡ‚Π΅Π°Π· — Ρ…ΠΈΠΌΠ°Π·Ρ‹ Ρ‚ΡƒΡ‡Π½Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΎΠΊ, катСпсин G Π½Π΅ΠΉΡ‚Ρ€ΠΎΡ„ΠΈΠ»ΠΎΠ², Π³Ρ€Π°Π½Π·ΠΈΠΌΡ‹ цитотоксичСских Π’-Π»ΠΈΠΌΡ„ΠΎΡ†ΠΈΡ‚ΠΎΠ² ΠΈ Π½Π°Ρ‚ΡƒΡ€Π°Π»ΡŒΠ½Ρ‹Ρ… ΠΊΠΈΠ»Π»Π΅Ρ€ΠΎΠ². Π”ΠΎ ΡΠΈΡ… ΠΏΠΎΡ€ ΠΈΡ… Ρ‚очная биологичСская Ρ€ΠΎΠ»ΡŒ Π½Π΅ ΡƒΡΡ‚Π°Π½ΠΎΠ²Π»Π΅Π½Π°, Π½ΠΎ ΠΌΠ½ΠΎΠ³ΠΎΡ‡ΠΈΡΠ»Π΅Π½Π½Ρ‹Π΅ Π΄Π°Π½Π½Ρ‹Π΅ ΡΠ²ΠΈΠ΄Π΅Ρ‚Π΅Π»ΡŒΡΡ‚Π²ΡƒΡŽΡ‚ ΠΎ Ρ‚ΠΎΠΌ, Ρ‡Ρ‚ΠΎ ΠΎΠ½ΠΈ ΠΈΠ³Ρ€Π°ΡŽΡ‚ Π²Π°ΠΆΠ½ΡƒΡŽ Ρ€ΠΎΠ»ΡŒ Π² ΠΈΠΌΠΌΡƒΠ½Π½ΠΎΠΌ ΠΎΡ‚Π²Π΅Ρ‚Π΅ ΠΎΡ€Π³Π°Π½ΠΈΠ·ΠΌΠ°, ΠΏΠΎΠ΄Π΄Π΅Ρ€ΠΆΠ°Π½ΠΈΠΈ гомСостаза, Ρ€Π°Π·Π²ΠΈΡ‚ΠΈΠΈ ряда патофизиологичСских процСссов. Π’Π°ΠΊ, Π½Π°ΠΏΡ€ΠΈΠΌΠ΅Ρ€, для Π³Ρ€Π°Π½Π·ΠΈΠΌΠΎΠ², А ΠΈ Π’ ΠΈΠ· цитотоксичСских Π’-Π»ΠΈΠΌΡ„ΠΎΡ†ΠΈΡ‚ΠΎΠ² ΠΏΠΎΠΊΠ°Π·Π°Π½ΠΎ, Ρ‡Ρ‚ΠΎ ΠΎΠ½ΠΈ ΡƒΡ‡Π°ΡΡ‚Π²ΡƒΡŽΡ‚ Π² Π·Π°ΠΏΡƒΡΠΊΠ΅ апоптичСских процСссов ΠΊΠ»Π΅Ρ‚ΠΎΠΊ-мишСнСй, инициируя каскад Π°ΠΊΡ‚ΠΈΠ²Π°Ρ†ΠΈΠΈ каспаз, Π²Π°ΠΆΠ½Ρ‹Ρ… Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚ΠΎΠ² Π°ΠΏΠΎΠΏΡ‚ΠΎΠ·Π°. ΠΠΊΡ‚ΠΈΠ²Π½ΠΎΡΡ‚ΡŒ катСпсина G ΡΠ²ΡΠ·Π°Π½Π° с Ρ„Π°Π³ΠΎΡ†ΠΈΡ‚ΠΎΠ·ΠΎΠΌ — Ρ„ΡƒΠ½ΠΊΡ†ΠΈΠ΅ΠΉ Π°Π·ΡƒΡ€ΠΎΡ„ΠΈΠ»ΡŒΠ½Ρ‹Ρ… Π³Ρ€Π°Π½ΡƒΠ», Π² ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Ρ… хранится Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚, -. ΠšΡ€ΠΎΠΌΠ΅ Ρ‚ΠΎΠ³ΠΎ, ΠΎΠ½ ΡΠΏΠΎΡΠΎΠ±Π΅Π½ Ρ€Π΅Π³ΡƒΠ»ΠΈΡ€ΠΎΠ²Π°Ρ‚ΡŒ Π°ΠΊΡ‚ΠΈΠ²Π½ΡƒΡŽ ΠΊΠΎΠ½Ρ†Π΅Π½Ρ‚Ρ€Π°Ρ†ΠΈΡŽ Ρ†ΠΈΡ‚ΠΎΠΊΠΈΠ½ΠΎΠ².

Π˜Π½Ρ‚Π΅Ρ€Π΅Ρ ΠΊ ΠΈΠ·ΡƒΡ‡Π΅Π½ΠΈΡŽ Π³Ρ€Π°Π½Π·ΠΈΠΌΠΎΠΏΠΎΠ΄ΠΎΠ±Π½Ρ‹Ρ… ΠΏΡ€ΠΎΡ‚Π΅Π°Π· ΠΊΠ»Π΅Ρ‚ΠΎΠΊ гСмопоэза Π½Π΅ ΠΎΡΠ»Π°Π±Π΅Π²Π°Π΅Ρ‚, Ρ‡Ρ‚ΠΎ обуславливаСтся участиСм Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚ΠΎΠ² этой Π³Ρ€ΡƒΠΏΠΏΡ‹ Π² ΠΆΠΈΠ·Π½Π΅Π½Π½ΠΎ Π²Π°ΠΆΠ½Ρ‹Ρ… процСссах ΠΎΡ€Π³Π°Π½ΠΈΠ·ΠΌΠ°. Число Π³Ρ€Π°Π½Π·ΠΈΠΌΠΎΠΏΠΎΠ΄ΠΎΠ±Π½Ρ‹Ρ… ΠΏΡ€ΠΎΡ‚Π΅Π°Π· постоянно пополняСтся Π½ΠΎΠ²Ρ‹ΠΌΠΈ, нСизвСстными Ρ€Π°Π½Π΅Π΅ прСдставитСлями.

Π‘ΠΎΠ»Π΅Π΅ Ρ‚ΠΎΠ³ΠΎ, послСдниС Π΄Π°Π½Π½Ρ‹Π΅ ΡΠ²ΠΈΠ΄Π΅Ρ‚Π΅Π»ΡŒΡΡ‚Π²ΡƒΡŽΡ‚ ΠΎ Ρ‚ΠΎΠΌ, Ρ‡Ρ‚ΠΎ ΠΈΡ… ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠ΅ происхоТдСниС ΠΌΠΎΠΆΠ΅Ρ‚ Π±Ρ‹Ρ‚ΡŒ ΡˆΠΈΡ€Π΅ ΠΈ Π½Π΅ ΠΎΠ³Ρ€Π°Π½ΠΈΡ‡ΠΈΠ²Π°Ρ‚ΡŒΡΡ Ρ‚ΠΎΠ»ΡŒΠΊΠΎ ΠΊΠ»Π΅Ρ‚ΠΊΠ°ΠΌΠΈ ΠΈΠΌΠΌΡƒΠ½Π½ΠΎΠΉ систСмы, ΡΠ»Π΅Π΄ΠΎΠ²Π°Ρ‚Π΅Π»ΡŒΠ½ΠΎ, Ρ€Π°ΡΡˆΠΈΡ€ΡΠ΅Ρ‚ΡΡ ΠΈ ΡΠΏΠ΅ΠΊΡ‚Ρ€ ΠΈΡ… Π΄Π΅ΠΉΡΡ‚вия.

Настоящая Ρ€Π°Π±ΠΎΡ‚Π° посвящСна исслСдованию Π½ΠΎΠ²ΠΎΠΉ сСриновой ΠΏΡ€ΠΎΡ‚Π΅Π°Π·Ρ‹, структурно Π±Π»ΠΈΠ·ΠΊΠΎΠΉ Π³Ρ€Π°Π½Π·ΠΈΠΌΠΎΠΏΠΎΠ΄ΠΎΠ±Π½Ρ‹ΠΌ ΠΏΡ€ΠΎΡ‚Π΅Π°Π·Π°ΠΌ (Ρ…ΠΈΠΌΠ°Π·ΠΎΠΏΠΎΠ΄ΠΎΠ±Π½ΠΎΠΉ ΠΏΡ€ΠΎΡ‚Π΅Π°Π·Ρ‹), ΠΎΠ±Π½Π°Ρ€ΡƒΠΆΠ΅Π½Π½ΠΎΠΉ Π² ΡΠ»ΠΈΠ·ΠΈΡΡ‚ΠΎΠΉ Π΄ΡƒΠΎΠ΄Π΅Π½ΡƒΠΌΠ° ΠΊΡ€ΡƒΠΏΠ½ΠΎΠ³ΠΎ Ρ€ΠΎΠ³Π°Ρ‚ΠΎΠ³ΠΎ скота Π² ΠΏΡ€ΠΎΡ†Π΅ΡΡΠ΅ систСматичСского изучСния Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚ΠΎΠ² Ρ‚ΠΎΠ½ΠΊΠΎΠ³ΠΎ ΠΊΠΈΡˆΠ΅Ρ‡Π½ΠΈΠΊΠ° ΠΌΠ»Π΅ΠΊΠΎΠΏΠΈΡ‚Π°ΡŽΡ‰ΠΈΡ…, ΠΏΡ€ΠΎΠ²ΠΎΠ΄ΠΈΠΌΠΎΠ³ΠΎ Π² Π»Π°Π±ΠΎΡ€Π°Ρ‚ΠΎΡ€ΠΈΠΈ Ρ…ΠΈΠΌΠΈΠΈ протСолитичСских Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚ΠΎΠ² Π˜Π‘Π₯. ЦСль настоящСго исслСдованияполучСниС высокоочищСнного ΠΏΡ€Π΅ΠΏΠ°Ρ€Π°Ρ‚Π° Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚Π°, ΠΈΠ·ΡƒΡ‡Π΅Π½ΠΈΠ΅ Π΅Π³ΠΎ Ρ„ΠΈΠ·ΠΈΠΊΠΎ-химичСских ΠΈ ΡΠ½Π·ΠΈΠΌΠ°Ρ‚ичСских свойств, ΠΎΠΏΡ€Π΅Π΄Π΅Π»Π΅Π½ΠΈΠ΅ ΠΊΠ»Π΅Ρ‚ΠΎΡ‡Π½ΠΎΠΉ Π»ΠΎΠΊΠ°Π»ΠΈΠ·Π°Ρ†ΠΈΠΈ Π½ΠΎΠ²ΠΎΠ³ΠΎ Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚Π°.

I. Π‘Π ΠΠ’ΠΠ˜Π’Π•Π›Π¬ΠΠΠ― Π₯ΠΠ ΠΠšΠ’Π•Π Π˜Π‘Π’Π˜ΠšΠ Π”Π£ΠžΠ”Π•ΠΠΠ—Π« И Π₯Π˜ΠœΠΠ—,.

Π€Π•Π ΠœΠ•ΠΠ’ΠžΠ’, БВРУКВУРНО Π ΠžΠ”Π‘Π’Π’Π•ΠΠΠ«Π₯ Π₯Π˜ΠœΠΠ—ΠžΠŸΠžΠ”ΠžΠ‘ΠΠžΠ™ ΠŸΠ ΠžΠ’Π•ΠΠ—Π• (Π»ΠΈΡ‚Π΅Ρ€Π°Ρ‚ΡƒΡ€Π½Ρ‹ΠΉ ΠΎΠ±Π·ΠΎΡ€).

Настоящий Π»ΠΈΡ‚Π΅Ρ€Π°Ρ‚ΡƒΡ€Π½Ρ‹ΠΉ ΠΎΠ±Π·ΠΎΡ€ посвящСн свойствам Π΄ΡƒΠΎΠ΄Π΅Π½Π°Π·Ρ‹ ΠΈ Ρ…ΠΈΠΌΠ°Π· — сСриновым ΠΏΡ€ΠΎΡ‚Π΅Π°Π·Π°ΠΌ, структурно ΠΈ ΡΠ½Π·ΠΈΠΌΠ°Ρ‚ичСски родствСнным исслСдуСмому Π½Π°ΠΌΠΈ Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚Ρƒ Ρ…ΠΈΠΌΠ°Π·ΠΎΠΏΠΎΠ΄ΠΎΠ±Π½ΠΎΠΉ ΠΏΡ€ΠΎΡ‚Π΅Π°Π·Π΅ (ChIP). РассмотрСниС свойств Π΄ΡƒΠΎΠ΄Π΅Π½Π°Π·Ρ‹ (ΠΏΠ΅Ρ€Π²Ρ‹ΠΉ Ρ€Π°Π·Π΄Π΅Π») прСдставляСтся интСрСсным Π² ΡΠ²ΡΠ·ΠΈ с Ρ‚Π΅ΠΌ, Ρ‡Ρ‚ΠΎ ChIP ΠΈ Π΄ΡƒΠΎΠ΄Π΅Π½Π°Π·Π° Π±Ρ‹Π»ΠΈ Π²Ρ‹Π΄Π΅Π»Π΅Π½Ρ‹ ΠΈΠ· ΠΎΠ΄Π½ΠΎΠ³ΠΎ источника (слизистая Π΄ΡƒΠΎΠ΄Π΅Π½ΡƒΠΌΠ° Π±Ρ‹ΠΊΠ°) ΠΈ ΠΎΠ±Π»Π°Π΄Π°ΡŽΡ‚ Π±Π»ΠΈΠ·ΠΊΠΈΠΌΠΈ молСкулярными ΠΈ Π½Π΅ΠΊΠΎΡ‚ΠΎΡ€Ρ‹ΠΌΠΈ энзиматичСскими свойствами. ΠšΡ€ΠΎΠΌΠ΅ Ρ‚ΠΎΠ³ΠΎ, Π΄ΡƒΠΎΠ΄Π΅Π½Π°Π·Π° являСтся СдинствСнным ΠΊ Π½Π°ΡΡ‚оящСму Π²Ρ€Π΅ΠΌΠ΅Π½ΠΈ ΠΎΡ…Π°Ρ€Π°ΠΊΡ‚Π΅Ρ€ΠΈΠ·ΠΎΠ²Π°Π½Π½Ρ‹ΠΌ прСдставитСлСм Π³Ρ€ΡƒΠΏΠΏΡ‹ Π³Ρ€Π°Π½Π·ΠΈΠΌΠΎΠΏΠΎΠ΄ΠΎΠ±Π½Ρ‹Ρ… ΠΏΡ€ΠΎΡ‚Π΅Π°Π· ΠΊΡ€ΡƒΠΏΠ½ΠΎΠ³ΠΎ Ρ€ΠΎΠ³Π°Ρ‚ΠΎΠ³ΠΎ скота, ΠΊ ΠΊΠΎΡ‚ΠΎΡ€ΠΎΠΉ относится исслСдуСмая Π² Π΄Π°Π½Π½ΠΎΠΉ Ρ€Π°Π±ΠΎΡ‚Π΅ ΠΏΡ€ΠΎΡ‚Π΅Π°Π·Π°. Π’Ρ‚ΠΎΡ€ΠΎΠΉ Ρ€Π°Π·Π΄Π΅Π» Π»ΠΈΡ‚Π΅Ρ€Π°Ρ‚ΡƒΡ€Π½ΠΎΠ³ΠΎ ΠΎΠ±Π·ΠΎΡ€Π° посвящСн свойствам Ρ…ΠΈΠΌΠ°Π· Ρ‚ΡƒΡ‡Π½Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΎΠΊ, Π°Π½Π°Π»ΠΎΠ³ΠΎΠΌ ΠΊΠΎΡ‚ΠΎΡ€Ρ‹Ρ… являСтся ΠΈΠ·ΡƒΡ‡Π°Π΅ΠΌΡ‹ΠΉ Π½Π°ΠΌΠΈ Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚.

Π²Ρ‹Π²ΠΎΠ΄Ρ‹.

1. Из ΡΠ»ΠΈΠ·ΠΈΡΡ‚ΠΎΠΉ Π΄ΡƒΠΎΠ΄Π΅Π½ΡƒΠΌΠ° Π±Ρ‹ΠΊΠ° с ΠΈΡΠΏΠΎΠ»ΡŒΠ·ΠΎΠ²Π°Π½ΠΈΠ΅ΠΌ Π°Ρ„Ρ„ΠΈΠ½Π½ΠΎΠΉ Ρ…Ρ€ΠΎΠΌΠ°Ρ‚ΠΎΠ³Ρ€Π°Ρ„ΠΈΠΈ Π½Π° ΠΊΠΎΠ»ΠΎΠ½ΠΊΠ΅ с ΠΈΠΌΠΌΠΎΠ±ΠΈΠ»ΠΈΠ·ΠΎΠ²Π°Π½Π½Ρ‹ΠΌ соСвым трипсиновым ΠΈΠ½Π³ΠΈΠ±ΠΈΡ‚ΠΎΡ€ΠΎΠΌ Π²Ρ‹Π΄Π΅Π»Π΅Π½Π° новая сСриновая ΠΏΡ€ΠΎΡ‚Π΅Π°Π·Π°. ΠŸΠΎΠ»ΡƒΡ‡Π΅Π½Π½Ρ‹ΠΉ ΠΏΡ€Π΅ΠΏΠ°Ρ€Π°Ρ‚ Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚Π° являСтся Π³ΠΎΠΌΠΎΠ³Π΅Π½Π½Ρ‹ΠΌ ΠΏΠΎ Π΄Π°Π½Π½Ρ‹ΠΌ N-ΠΊΠΎΠ½Ρ†Π΅Π²ΠΎΠ³ΠΎ сСквСнирования, элСктрофорСза, ΠΎΠ±Ρ€Π°Ρ‰Π΅Π½Π½ΠΎ-Ρ„Π°Π·ΠΎΠ²ΠΎΠΉ Ρ…Ρ€ΠΎΠΌΠ°Ρ‚ΠΎΠ³Ρ€Π°Ρ„ΠΈΠΈ ΠΈ Π³Π΅Π»ΡŒ-Ρ„ΠΈΠ»ΡŒΡ‚Ρ€Π°Ρ†ΠΈΠΈ.

2. ΠœΠ΅Ρ‚ΠΎΠ΄ΠΎΠΌ масс-спСктромСтрии (MALDI-MS) установлСно, Ρ‡Ρ‚ΠΎ молСкулярная масса Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚Π° составляСт 24,97 ΠΊΠ”Π°. Π€Π΅Ρ€ΠΌΠ΅Π½Ρ‚ являСтся ΠΌΠΎΠ½ΠΎΠΌΠ΅Ρ€ΠΎΠΌ, состоящим ΠΈΠ· ΠΎΠ΄Π½ΠΎΠΉ ΠΏΠΎΠ»ΠΈΠΏΠ΅ΠΏΡ‚ΠΈΠ΄Π½ΠΎΠΉ Ρ†Π΅ΠΏΠΈ.

3. ΠžΠΏΡ€Π΅Π΄Π΅Π»Π΅Π½Π° N-концСвая ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°Ρ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚ΡŒ Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚Π° (23 аминокислоты) — наибольшая ΡΡ‚Π΅ΠΏΠ΅Π½ΡŒ структурной Π³ΠΎΠΌΠΎΠ»ΠΎΠ³ΠΈΠΈ обнаруТиваСтся с ΡΠΎΠΎΡ‚Π²Π΅Ρ‚ΡΡ‚Π²ΡƒΡŽΡ‰ΠΈΠΌΠΈ участками ΠΏΠΎΡΠ»Π΅Π΄ΠΎΠ²Π°Ρ‚Π΅Π»ΡŒΠ½ΠΎΡΡ‚ΠΈ Ρ…ΠΈΠΌΠ°Π· Ρ‚ΡƒΡ‡Π½Ρ‹Ρ… ΠΊΠ»Π΅Ρ‚ΠΎΠΊ.

4. На ΠΎΡΠ½ΠΎΠ²Π°Π½ΠΈΠΈ ΡΡ€Π°Π²Π½ΠΈΡ‚Π΅Π»ΡŒΠ½ΠΎΠ³ΠΎ Π°Π½Π°Π»ΠΈΠ·Π° Π΄Π°Π½Π½Ρ‹Ρ… ΠΏΠΎ Π³ΠΈΠ΄Ρ€ΠΎΠ»ΠΈΠ·Ρƒ исслСдуСмой ΠΏΡ€ΠΎΡ‚Π΅Π°Π·ΠΎΠΉ ΠΏΡ€ΠΈΡ€ΠΎΠ΄Π½Ρ‹Ρ… ΠΈ ΡΠΈΠ½Ρ‚СтичСских субстратов установлСно, Ρ‡Ρ‚ΠΎ ΡΠΏΠ΅Ρ†ΠΈΡ„ΠΈΡ‡Π½ΠΎΡΡ‚ΡŒ, проявляСмая Сю (Π² ΠΏΠΎΠ»ΠΎΠΆΠ΅Π½ΠΈΡΡ… Π 1-Π Π’), Ρ…Π°Ρ€Π°ΠΊΡ‚Π΅Ρ€Π½Π° для ряда Ρ…ΠΈΠΌΠ°Π·.

5. ИсслСдовано ΠΈΠ½Π³ΠΈΠ±ΠΈΡ€ΡƒΡŽΡ‰Π΅Π΅ дСйствиС Π½Π° ΠΈΠ·ΡƒΡ‡Π°Π΅ΠΌΡƒΡŽ ΠΏΡ€ΠΎΡ‚Π΅Π°Π·Ρƒ ряда синтСтичСских ΠΈ Π±Π΅Π»ΠΊΠΎΠ²Ρ‹Ρ… ΠΈΠ½Π³ΠΈΠ±ΠΈΡ‚ΠΎΡ€ΠΎΠ² сСриновых ΠΏΡ€ΠΎΡ‚Π΅Π°Π·. УстановлСно, Ρ‡Ρ‚ΠΎ, ΠΏΠΎΠ΄ΠΎΠ±Π½ΠΎ Ρ…ΠΈΠΌΠ°Π·Π°ΠΌ, Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚ Π½Π°ΠΈΠ±ΠΎΠ»Π΅Π΅ эффСктивно ингибируСтся Π±Π΅Π»ΠΊΠΎΠ²Ρ‹ΠΌΠΈ ΠΈΠ½Π³ΠΈΠ±ΠΈΡ‚ΠΎΡ€Π°ΠΌΠΈ Ρ‚ΠΈΠΏΠ° ΠšΡƒΠ½ΠΈΡ‚Ρ†Π° ΠΈ Π‘Π°ΡƒΠΌΠ°Π½Π°-Π‘ΠΈΡ€ΠΊ ΠΈΠ· Π±ΠΎΠ±ΠΎΠ²Ρ‹Ρ…, Π½ΠΎ ΠΏΡ€ΠΎΡΠ²Π»ΡΠ΅Ρ‚ ΡƒΡΡ‚ΠΎΠΉΡ‡ΠΈΠ²ΠΎΡΡ‚ΡŒ ΠΊ Π΄Π΅ΠΉΡΡ‚Π²ΠΈΡŽ панкрСатичСского трипсинового ΠΈΠ½Π³ΠΈΠ±ΠΈΡ‚ΠΎΡ€Π° BPTI.

6. Π‘ΠΎΠ²ΠΎΠΊΡƒΠΏΠ½ΠΎΡΡ‚ΡŒ ΠΏΠΎΠ»ΡƒΡ‡Π΅Π½Π½Ρ‹Ρ… Π² Ρ€Π°Π±ΠΎΡ‚Π΅ Π΄Π°Π½Π½Ρ‹Ρ… позволяСт ΠΏΡ€Π΅Π΄ΠΏΠΎΠ»ΠΎΠΆΠΈΡ‚ΡŒ, Ρ‡Ρ‚ΠΎ ΠΎΠ±Π½Π°Ρ€ΡƒΠΆΠ΅Π½Π½Ρ‹ΠΉ Π½Π°ΠΌΠΈ ΠΈ Π²Ρ‹Π΄Π΅Π»Π΅Π½Π½Ρ‹ΠΉ Π² ΠΈΠ½Π΄ΠΈΠ²ΠΈΠ΄ΡƒΠ°Π»ΡŒΠ½ΠΎΠΌ состоянии Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚ относится ΠΊ Ρ…ΠΈΠΌΠ°Π·Π°ΠΌ. Для этого Ρ„Π΅Ρ€ΠΌΠ΅Π½Ρ‚Π° прСдлагаСтся Π½Π°Π·Π²Π°Π½ΠΈΠ΅ Π±Ρ‹Ρ‡ΡŒΡ химазоподобная ΠΏΡ€ΠΎΡ‚Π΅Π°Π·Π°.

ΠŸΠΎΠΊΠ°Π·Π°Ρ‚ΡŒ вСсь тСкст

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