Thermally Reversible Hydrogels via Intramolecular Folding and Consequent Self-Assembly of a de Novo Designed Peptide

• Published in: Journal of the American Chemical Society 2003-10, Vol.125 (39), p.11802-11803
• Main Authors: Pochan, Darrin J, Schneider, Joel P, Kretsinger, Juliana, Ozbas, Bulent, Rajagopal, Karthikan, Haines, Lisa
• Format: Article
• Language: English
• Subjects: Amino Acid Sequence; Biological and medical sciences; Circular Dichroism; Disperse state. Micelles; Fundamental and applied biological sciences. Psychology; Hot Temperature; Hydrogels - chemistry; Hydrogen-Ion Concentration; Hydrophobic and Hydrophilic Interactions; Molecular biophysics; Molecular Sequence Data; Peptides - chemistry; Physico-chemical properties of biomolecules; Protein Folding
• ISSN: 0002-7863; 1520-5126
• DOI: 10.1021/ja0353154

A small de novo designed peptide (MAX3) is described that exhibits complete thermoreversible self-assembly into a hydrogel network. Importantly, a prerequisite to hydrogelation is that the peptide must first fold into a conformation conducive to self-assembly. At ambient temperature, MAX3 is unfolded, resulting in a low viscosity aqueous solution. On increasing the temperature, the peptide undergoes a unimolecular folding event, affording an amphiphilic β-hairpin that consequently self-assembles into a hydrogel network. Increasing the temperature serves to dehydrate the nonpolar residues of the unfolded peptide and trigger folding via hydrophobic collapse. Cooling the resultant hydrogel results in β-hairpin unfolding and consequent complete dissolution of the hydrogel. The temperature at which folding and consequent self-assembly into a rigid hydrogel occur can be tuned by altering the hydrophobicity of the peptides.