Honors Theses
Date of Award
12-2018
Document Type
Thesis
Department
Biology
First Advisor
Dr. Yonghong Zhang
Second Advisor
Dr. Shizue Mito
Third Advisor
Dr. James M. Bullard
Abstract
The αvβ3 integrin, a receptor for many extracellular matrix proteins with the RGD sequence motif, is involved in multiple physiological processes. The integrin is highly expressed on tumor cells, therefore making it a target for cancer therapy and imaging. Efforts have been made to develop an RGD-containing ligand against the αvβ3 integrin.
A series of RGD-containing cyclic octapeptides (LXW analogs) were previously synthesized, tested in vitro, and screened as integrin antagonists with a different binding affinity (Xiao et al., 2010; Wang et al., 2015), but the structure-activity relationship remains to be elucidated. In the current study, the structures of three representative LXW octapeptides were determined by solution NMR and then docked to the integrin for complex structure models. The structural comparisons and docking studies showed that the hydrophobicity of the X7 position of LXW analogs plays a critical role in advancing binding affinity to the integrin.
A comparison was made between in vitro and computational docking experiments to examine the resourcefulness and efficiency of receptor-ligand docking. Consistency within the results of both methods was found, leading to the continuous optimization and testing of the LXW peptides via computation docking screening.
Through our docking results, we have identified several new and potentially improved RGD-containing cyclic octapeptide sequences against the αvβ3 integrin.
Recommended Citation
Silva, A. (2018). Structure-Activity Relationship of Novel RGD-Containing Cyclic Peptides Against αvβ3 Integrin [Undergraduate honors thesis]. Scholarworks @ UTRGV. https://scholarworks.utrgv.edu/honors/8
Comments
Copyright 2018 Aaron Silva. All Rights Reserved.