Date of Award

Spring 2013

Document Type

Restricted Thesis

Terms of Use

© 2013 Rebecca M. Hammond. All rights reserved. Access to this work is restricted to users within the Swarthmore College network and may only be used for non-commercial, educational, and research purposes. Sharing with users outside of the Swarthmore College network is expressly prohibited. For all other uses, including reproduction and distribution, please contact the copyright holder.

Degree Name

Bachelor of Arts

Department

Biology Department

First Advisor

Amy Cheng Vollmer

Abstract

Human Immunodeficiency Virus (HIV) affects millions of individuals worldwide. The primary mode of transmission of the virus is through sexual intercourse. Peptides found in human semen form amyloid fibrils that promote HIV transmission. The proteins semenogelin I (SEM1) and semenogelin II (SEM2), which make up the primary component of the semen coagulum, are proteolytically cleaved to smaller fragments that form such amyloid fibrils. Here, SEM1(45-107) and SEM2(49-107) amyloid fibrils were formed under various conditions. Then several small molecules were tested against the fibrils for amyloid disaggregation activity. Neither peptide showed consistent assembly kinetics in any buffer used. SEM1 and SEM2 showed accelerated aggregation into small, potentially off-pathway aggregates when dissolved in a semen simulant or an anionic phosphate buffer. Both exhibited the same responses to the three small molecules tested. The polyphenol epigallocatechin gallate (EGCG) showed disaggregation activity almost immediately upon incubation with SEM1 and SEM2 amyloid fibrils. EGCG was also tested against fibrils of the prostatic acid phosphatase fragment PAP85-120, another HIV infection- enhancing amyloidogenic peptide found in semen. Disaggregation occurred more slowly for amyloid of this peptide, indicating a difference in fibril structure that affects interaction with EGCG. The molecular tweezer CLR01, which has previously been found to disaggregate the semen-derived amyloid SEVI (for Semen-derived Enhancer of Virus Infection), did not show disaggregation activity on SEM1 or SEM2. γ-amino orceinimine, a component of orcein, was found to reduce ThT fluorescence in the absence of fibril remodeling activity. Collaborators have subsequently shown that both EGCG and CLR01 reduce the HIV infection-enhancing properties of SEMl(45-107). These findings highlight the potential of EGCG and CLR01 as preventive tools against HIV transmission.

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