Poly(sarcosine)-block-oligo(l-tryptophan) Copolymers as Noncovalent Inhibitors of Protein Aggregation

Area of Science:

• Biochemistry
• Polymer Chemistry
• Materials Science

Background:

• Protein aggregation causes loss of function, impacting biotherapeutics, biocatalysis, and food industries.
• Current storage and transport methods rely heavily on cold chains, increasing costs and carbon footprint.
• There is a need for novel tools to prevent protein aggregation for ambient temperature logistics.

Purpose of the Study:

• To synthesize and evaluate novel block copolymers for inhibiting protein aggregation.
• To develop a strategy for stabilizing proteins at ambient temperatures, reducing cold chain dependence.
• To explore poly(sarcosine) as a biocompatible alternative to poly(ethylene glycol) in protein stabilization.

Main Methods:

• Synthesis of block copolymers using N-carboxyanhydride polymerization.
• Incorporation of oligo-tryptophan tails to target aggregation-prone protein regions.
• Utilizing poly(sarcosine) as a hydrophilic and biocompatible solubility block.
• Testing aggregation inhibition using lysozyme as a model protein under agitation stress.

Main Results:

• Block copolymers with oligo-tryptophan tails effectively inhibited lysozyme aggregation.
• Poly(sarcosine) demonstrated good biocompatibility and low toxicity.
• Hydrophobic amino acid blocks alone were insoluble and ineffective.
• Random copolymers showed no protein aggregation inhibition activity, emphasizing the importance of block structure.

Conclusions:

• Novel block copolymers effectively prevent protein aggregation, offering a solution for ambient temperature storage and transport.
• The specific block structure and hydrophobic residue choice are critical for effective protein stabilization.
• Poly(sarcosine)-based block copolymers present a promising, low-toxicity alternative for biopharmaceutical applications.