Search In this Thesis
   Search In this Thesis  
العنوان
Rational Design and Synthesis of Cell Penetrating Peptide Modulators of Signal Transduction Events in Cancer Cells /
المؤلف
Osman, Shaimaa Mahdy Mohamed.
هيئة الاعداد
باحث / شيماء مهدى محمد عثمان
مشرف / عبدالجواد محمد ربيع
مشرف / محمد على زويل
مشرف / أحمد محمد شلبى
تاريخ النشر
2019.
عدد الصفحات
241 p. :
اللغة
الإنجليزية
الدرجة
الدكتوراه
التخصص
Organic Chemistry
تاريخ الإجازة
1/1/2019
مكان الإجازة
جامعة عين شمس - كلية العلوم - الكيمياء
الفهرس
Only 14 pages are availabe for public view

from 241

from 241

Abstract

The cell membrane often represents a challenging obstacle to the intracellular transportation of many molecules. The active delivery of drugs through such barrier often requires specific carriers of high ability to cross the lipid bilayer. Cell penetrating peptides (CPPs) are generally short sequences of about 5–30 amino acids long which widely used to transport such molecules inside the cells because they are highly able to cross cell membranes, are. Generally, CPPs are still difficult to be exactly defined because of the uncertainties around their precise translocating mechanisms. However, CPPs are still useful in studying many intracellular mechanisms and promoting future development of novel drugs. The term bioportides is introduced by Howl’s group, University of Wolverhampton, to characterize bioactivities cell penetrating peptides from commonly inert CPP vectors.
Peptide synthesis with a well-defined sequence of amino acid is a complex process. Methodology researches are required to find different improved techniques for peptide synthesis with a wide range of chemicals and reaction conditions.
The chemical synthesis of peptides has made a great progress in the last decades especially after introduction of Modern Solid Phase Peptide Synthesis that is reliable, cost-effective and can be easily fully automated.
In the presented work, QSAR analysis have been utilized to identify CPPs within C-Kit protein receptor, a 976 AA protein, that is normally expressed in many cells including mast cells, promoting proliferation, migration, and survival. The used RBL-2H3 leukemic cell line is an accepted Mast cell model system.
The selected sequences were from the cytoplasmic part of the protein, and consists a Tyrosine phosphorylation active site and an α helix, to find some bioactive cell penetrating peptides (Bioportides) from the c-Kit protein.
Using microwave assisted solid phase peptide synthesizer, the following peptide sequences between 10 to 20 aa, have been synthesized, where (p) represents the phosphotyrosine containing analogue sequence: