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Therapeutic protein aggregation: mechanisms, design, and control

Paper ID Volume ID Publish Year Pages File Format Full-Text
37051 45303 2014 9 PDF Available
Title
Therapeutic protein aggregation: mechanisms, design, and control
Abstract

•Therapeutic proteins form a variety of aggregate types.•Aggregates are risk factors for patient immune responses.•Aggregation mechanisms depend on protein sequence and environment.•Opportunities exist for predictive design and control of aggregation rates and mechanisms.

Although it is well known that proteins are only marginally stable in their folded states, it is often less well appreciated that most proteins are inherently aggregation-prone in their unfolded or partially unfolded states, and the resulting aggregates can be extremely stable and long-lived. For therapeutic proteins, aggregates are a significant risk factor for deleterious immune responses in patients, and can form via a variety of mechanisms. Controlling aggregation using a mechanistic approach may allow improved design of therapeutic protein stability, as a complement to existing design strategies that target desired protein structures and function. Recent results highlight the importance of balancing protein environment with the inherent aggregation propensities of polypeptide chains.

Keywords
protein aggregation; protein stability; protein interactions; computational design
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Publisher
Database: Elsevier - ScienceDirect
Journal: - Volume 32, Issue 7, July 2014, Pages 372–380
Authors
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Subjects
Physical Sciences and Engineering Chemical Engineering Bioengineering
Get Full-Text Now
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Price was $35.95
You save - $31
Price after discount Only $4.95
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