To access this work you must either be on the Smith College campus OR have valid Smith login credentials.

On Campus users: To access this work if you are on campus please Select the Download button.

Off Campus users: To access this work from off campus, please select the Off-Campus button and enter your Smith username and password when prompted.

Non-Smith users: You may request this item through Interlibrary Loan at your own library.

Publication Date

2021

First Advisor

Sarah J. Moore

Document Type

Honors Project

Degree Name

Bachelor of Science

Department

Engineering

Keywords

Cancer, Targeted cancer therapy, Targeted drug delivery, Fibronectin, Protein engineering, Polymer, Protein-polymer conjugation, Integrin, Polymerization, Ligand-protein docking, Computational drug discovery, Structural prediction

Abstract

Current cancer drug delivery methods target both rapidly dividing cancer cells and healthy cells. As a result cancer patients face many harmful side effects. By using a targeted drug delivery method, these harmful side effects may be minimized while still effectively treating cancer. An approach to targeted drug delivery is using protein-polymer conjugates (PPCs) as a drug delivery system. A PPC will allow for targeted drug delivery to the cancer site while overcoming many of the limitations current drug delivery methods present. The goal of this thesis is to computationally model a PPC to assess its structural interactions and behaviors to make informative predictions about the targeted drug delivery system.

The PPC consists of an engineered protein that has the ability to bind to a drug loaded polymer as well as bind to an expressed integrin on cancer cell surfaces. First, a model of the engineered protein was obtained using the I-TASSER web-based software. PyMol was then used to determine if the engineered protein had the ability to bind to the αvβ3 integrin receptor at their respective RGD sites. Finally, a complete model of the PPC was obtained once a polymer mimic was attached to a cysteine tag of the engineered protein. With the complete PPC model, a polymer length analysis was done to predict the optimal polymer length for drug loading and limiting binding site blocking. It was concluded that polymer lengths of 50 azlactone repeat units or less was best. For future work, an experimental structural analysis will be done to confirm the computational results obtained as well as binding studies with a cancer cell expressing the αvβ3 integrin.

Rights

©2021. Jessica Bonsu.

Language

English

Comments

49 pages : illustrations (chiefly color) Includes bibliographical references (pages 44-49)

Download

Smith Only:
Off Campus Download

Share

COinS