The Pentablock Amphiphilic Copolymer T1107 Prevents Aggregation of Denatured and Reduced Lysozyme.
Aggregation of denatured or unfolded proteins establishes a large energy barrier to spontaneous recovery of protein form and function following traumatic injury, tissue cryopreservation, and biopharmaceutical storage. Some tissues utilize small heat shock proteins (sHSPs) to prevent irreversible aggregation, which allows more complex processes to refold or remove the unfolded proteins. It is postulated that large, amphiphilic, and biocompatible block copolymers can mimic sHSP function. Reduced and denatured hen egg white lysozyme (HEWL) is used as a model aggregating protein. The poloxamine T1107 prevents aggregation of HEWL at 37 °C by three complimentary measures. Structural analysis of denatured HEWL reveals a partially folded conformation with preserved or promoted beta-sheet structures only in the presence of T1107. The physical association of T1107 with denatured HEWL, and the ability to prevent aggregation, is linked to the critical micelle temperature of the polymer. The results suggest that T1107, or a similar amphiphilic block copolymer, can find use as a synthetic chaperone to augment the innate molecular repair mechanisms of natural cells.
Department of Surgery, The University of Chicago, Chicago, IL, 60637, USA.
Michael J
MJ
Poellmann
Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, 60637, USA.|Institute for Biophysical Dynamics, Computation Institute, The University of Chicago, Chicago, IL, 60637, USA.
Tobin R
TR
Sosnick
Department of Biochemistry and Molecular Biology, The University of Chicago, Chicago, IL, 60637, USA.|Department of Pathology, Department of Neurology, The University of Chicago, Chicago, IL, 60637, USA.
Stephen C
SC
Meredith
Department of Surgery, The University of Chicago, Chicago, IL, 60637, USA.|Department of Organismal Biology and Anatomy, Institute for Molecular Engineering, The University of Chicago, Chicago, IL, 60637, USA.
Raphael C
RC
Lee
D000818:Animals; D002417:Cattle; D002942:Circular Dichroism; D004229:Dithiothreitol / Q000494:pharmacology; D000067493:Dynamic Light Scattering; D005029:Ethylenediamines / Q000737:chemistry; D009113:Muramidase / Q000737:chemistry*; D010084:Oxidation-Reduction; D010316:Particle Size; D066329:Protein Aggregates; D011489:Protein Denaturation / Q000187:drug effects; D013050:Spectrometry, Fluorescence; D013501:Surface-Active Agents / Q000737:chemistry*; D014364:Tryptophan / Q000378:metabolism
D005029:Ethylenediamines; D066329:Protein Aggregates; D013501:Surface-Active Agents; C112299:Tetronic 1107; D014364:Tryptophan; C421864:hen egg lysozyme; D009113:Muramidase; D004229:Dithiothreitol
P188; T1107; chaperone; lysozyme; poloxamer; poloxamine