Synthesis and Investigation of Backbone Modified Squaramide Dipeptide Self-Assembly

• Published in: ACS applied bio materials Vol. 6; no. 2; pp. 507 - 518
• Main Authors: Shinde, Suchita Dattatray, Kulkarni, Neeraj, Sahu, Bichismita
• Format: Journal Article
• Language: English
• Published: United States American Chemical Society 20.02.2023
• Subjects: Dipeptides - chemistry; Hydrogels; Peptides; Quinine; molecular self-assembly; low molecular weight hydrogelator; squaramide; backbone modified dipeptide; enzymatic stability
• ISSN: 2576-6422; 2576-6422
• DOI: 10.1021/acsabm.2c00803

Dipeptides are minimalistic peptide building blocks that form well ordered structures through molecular self-assembly. The driving forces involved are cooperative noncovalent interactions such as π–π stacking, hydrogen bonding, and ionic as well as hydrophobic interactions. One of the most intriguing self-assembled motifs that has been extensively explored as a low molecular weight hydrogel for drug delivery, tissue engineering, imaging and techtonics, etc. is Phe-Phe (FF). The backbone of the dipeptide is very crucial for extending secondary structures in self-assembly, and any subtle change in the backbone drastically affect the molecular recognitions. The squaramide (SQ) motif has the unique advantage of hydrogen bonding which can promote the self-assembly process. In this work we have integrated the SQ unit into the dipeptide FF backbone to achieve molecular self-assembly. The resulting carbamate protected backbone modified dipeptide (BocFSAF-OH, 10) has exhibited molecular self-assembly with a fibrilar network. It formed a stable hydrogel (with CAC of 0.024 ± 0.0098 wt %) via the solvent switch method and was found to possess excellent enzymatic stability. The dipeptide and the resulting hydrogel were found to be cytocompatible. When integrated with a polysaccharide based biopolymer, e.g. sodium alginate, the resulting matrix exhibited strong hydrogel character. Therefore, the dipeptide hydrogel of 10 may find its applications in a variety of fields including drug delivery and tissue engineering.