Synthesis of disulfide fragments for use in high throughput disulfide-exchange screening

Presenter's Name(s)

Sawyer Davis

Abstract

Historically, therapeutic compounds were discovered by chance, often through medicinal plants. Today, drug discovery relies on screening large libraries of single compounds against disease-associated pathways to identify promising candidates. Disulfide fragments selectively bind cysteine residues within protein binding grooves, forming covalent bonds detectable via mass spectrometry. Their synthesis involves two simple steps: amide coupling and disulfide exchange, followed by purification. Binding affinity and selectivity are assessed through biochemical assays and dose-response experiments. This poster explores the application of disulfides in scaffolding protein 14-3-3 and its disease-associated client, estrogen receptor alpha (ERα), highlighting their potential role in targeted drug discovery.

Primary Faculty Mentor Name

Alexander Wurthmann

Status

Undergraduate

Student College

College of Arts and Sciences

Program/Major

Biology

Primary Research Category

Life Sciences

Abstract only.

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Synthesis of disulfide fragments for use in high throughput disulfide-exchange screening

Historically, therapeutic compounds were discovered by chance, often through medicinal plants. Today, drug discovery relies on screening large libraries of single compounds against disease-associated pathways to identify promising candidates. Disulfide fragments selectively bind cysteine residues within protein binding grooves, forming covalent bonds detectable via mass spectrometry. Their synthesis involves two simple steps: amide coupling and disulfide exchange, followed by purification. Binding affinity and selectivity are assessed through biochemical assays and dose-response experiments. This poster explores the application of disulfides in scaffolding protein 14-3-3 and its disease-associated client, estrogen receptor alpha (ERα), highlighting their potential role in targeted drug discovery.