Klorotoksin Peptit Yapısına Dayalı Matriks Metalloproteinaz-2 İnhibitörlerinin Geliştirilmesi

ÖZEN, Can; ÖZÇUBUKÇU, Salih

Klorotoksin Peptit Yapısına Dayalı Matriks Metalloproteinaz-2 İnhibitörlerinin Geliştirilmesi

Yürütücü

Salih ÖZÇUBUKÇU (Orta Doğu Teknik Üniversitesi, Fen Edebiyat Fakültesi, Kimya Bölümü, Ankara, Türkiye)

Araştırmacı(lar)

Can ÖZEN (Boş)

4 0

Proje Grubu: KBAG Sayfa Sayısı: 77 Proje No: 214Z083 Proje Bitiş Tarihi: 01.11.2017 Metin Dili: Türkçe İndeks Tarihi: 27-01-2020

Klorotoksin Peptit Yapısına Dayalı Matriks Metalloproteinaz-2 İnhibitörlerinin Geliştirilmesi

Öz:

Bu projenin amacı, kanser gibi temel hastalıkların terapisinde önemli bir moleküler hedef olan MMP-2 enzimine spesifik, klorotoksin peptit yapısına dayalı, yüksek etkinlikte ve seçicilikte özgün bir inhibitör geliştirmektir. Geliştirilmeye çalışılan inhibitör, 36 amino asitten oluşan (4 kDa) ve akrep zehrinden izole edilmiş seçici bir MMP-2 inhibitörü olan klorotoksin (CLTX) peptidinin yapısına dayanmaktadır. Proje stratejisi, ön çalışmalarımız sonucu CLTX yapısında belirlediğimiz dört kritik pozisyonda (H10, K15, K23 ve K27) farklı karbon zinciri eklemeleriyle toplam 20 adet tiyol ve azido alanin modifikasyonu gerçekleştirerek MMP-2 yapısındaki çinko elementine koordinasyon sağlama prensibine dayanmaktadır. Proje süresinde lizin modifikasyonlarda sentezlerdeki sıkıntılardan dolayı strateji değiştirmeye gidilmesi gerekmiştir. Bu nedenle her bir lizinden 3 farklı modifikasyon sentezlenmiş ancak bunlardan da ikişer tanesinin katlanması başarı ile gerçekleşmiştir. Histidin modifikasyonu model peptitte başarılı olunmasına rağmen esas peptitte click tepkimesinin başarısızlığı nedeniyle gerçekleşememiştir. Elde edilen CLTX türevlerinin MMP-2 aktiviteleri ölçülmüş ancak beklenen aksine inhibe etmek yerine aktive ettiği görülmüştür.

Anahtar Kelime: rasyonel ilaç tasarımı peptit inhibitör klorotoksin matriks metalloproteinaz kanser yapısal biyoloji

Konular: Kimya, Organik Kimya, Tıbbi Biyokimya ve Moleküler Biyoloji

Erişim Türü: Erişime Açık

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APA	ÖZÇUBUKÇU S, ÖZEN C (2017). Klorotoksin Peptit Yapısına Dayalı Matriks Metalloproteinaz-2 İnhibitörlerinin Geliştirilmesi. , 1 - 77.
Chicago	ÖZÇUBUKÇU Salih,ÖZEN Can Klorotoksin Peptit Yapısına Dayalı Matriks Metalloproteinaz-2 İnhibitörlerinin Geliştirilmesi. (2017): 1 - 77.
MLA	ÖZÇUBUKÇU Salih,ÖZEN Can Klorotoksin Peptit Yapısına Dayalı Matriks Metalloproteinaz-2 İnhibitörlerinin Geliştirilmesi. , 2017, ss.1 - 77.
AMA	ÖZÇUBUKÇU S,ÖZEN C Klorotoksin Peptit Yapısına Dayalı Matriks Metalloproteinaz-2 İnhibitörlerinin Geliştirilmesi. . 2017; 1 - 77.
Vancouver	ÖZÇUBUKÇU S,ÖZEN C Klorotoksin Peptit Yapısına Dayalı Matriks Metalloproteinaz-2 İnhibitörlerinin Geliştirilmesi. . 2017; 1 - 77.
IEEE	ÖZÇUBUKÇU S,ÖZEN C "Klorotoksin Peptit Yapısına Dayalı Matriks Metalloproteinaz-2 İnhibitörlerinin Geliştirilmesi." , ss.1 - 77, 2017.
ISNAD	ÖZÇUBUKÇU, Salih - ÖZEN, Can. "Klorotoksin Peptit Yapısına Dayalı Matriks Metalloproteinaz-2 İnhibitörlerinin Geliştirilmesi". (2017), 1-77.

APA	ÖZÇUBUKÇU S, ÖZEN C (2017). Klorotoksin Peptit Yapısına Dayalı Matriks Metalloproteinaz-2 İnhibitörlerinin Geliştirilmesi. , 1 - 77.
Chicago	ÖZÇUBUKÇU Salih,ÖZEN Can Klorotoksin Peptit Yapısına Dayalı Matriks Metalloproteinaz-2 İnhibitörlerinin Geliştirilmesi. (2017): 1 - 77.
MLA	ÖZÇUBUKÇU Salih,ÖZEN Can Klorotoksin Peptit Yapısına Dayalı Matriks Metalloproteinaz-2 İnhibitörlerinin Geliştirilmesi. , 2017, ss.1 - 77.
AMA	ÖZÇUBUKÇU S,ÖZEN C Klorotoksin Peptit Yapısına Dayalı Matriks Metalloproteinaz-2 İnhibitörlerinin Geliştirilmesi. . 2017; 1 - 77.
Vancouver	ÖZÇUBUKÇU S,ÖZEN C Klorotoksin Peptit Yapısına Dayalı Matriks Metalloproteinaz-2 İnhibitörlerinin Geliştirilmesi. . 2017; 1 - 77.
IEEE	ÖZÇUBUKÇU S,ÖZEN C "Klorotoksin Peptit Yapısına Dayalı Matriks Metalloproteinaz-2 İnhibitörlerinin Geliştirilmesi." , ss.1 - 77, 2017.
ISNAD	ÖZÇUBUKÇU, Salih - ÖZEN, Can. "Klorotoksin Peptit Yapısına Dayalı Matriks Metalloproteinaz-2 İnhibitörlerinin Geliştirilmesi". (2017), 1-77.