Document Type

Honors Capstone Project

Date of Submission

Spring 5-1-2013

Capstone Advisor

James C Dabrowiak, Ph.D.

Honors Reader

Surabhi Raina, Ph.D.

Capstone Major

Biology

Capstone College

Arts and Science

Audio/Visual Component

no

Capstone Prize Winner

no

Won Capstone Funding

no

Honors Categories

Sciences and Engineering

Subject Categories

Biochemistry | Biology | Chemistry

Abstract

The transcription factor p53 can induce apoptosis and cell cycle arrest in response to cellular distress. Cancer cells often display increased cell survival. In most cases, this is due to a p53-related defect, such as mutation, deletion, degradation, or sequestration. HDM2 and HDMX are homologous proteins that regulate the function of p53, and their over-expression can lead to an ineffective p53 response. Various inhibitors, including hydrocarbon stabilized alpha-helices of p53 (SAH-p53s), have been developed to target HDM2 and HDMX and restore functionality to the p53 pathway. It has been recently found that SAH-p53 factors also elicit cell death responses in the absence of transcriptionally active p53. In order to investigate other potential targets of SAH-p53, a protocol was developed based on a paper by Craig Braun 11 which discusses a mechanism utilizing photoactivatable amino substitutions to capture binding partners covalently. Using this protocol, p53-derived stapled peptides were found to bind selectively to p53’s known target, HDM2 as well as other unknown proteins. The various p53-derived stapled peptides were utilized to obtain further insight into the p53-derived stapled peptide targets.

Creative Commons License

Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License
This work is licensed under a Creative Commons Attribution-Noncommercial-No Derivative Works 3.0 License.

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