Design of Fibril-Forming and Cell-Adhesive Peptides Conjugated with Non-Natural Functional Groups Based on Molecular Descriptors

We developed a molecular descriptor-based strategy for designing fibril-forming and cell-adhesive peptides conjugated with non-natural functional groups for biomaterial applications. Twenty-one peptides were prepared by introducing one of the 20 standard amino acids at the N-terminus of the fibril-forming core sequence NFGAIL. Their fibril-forming properties were evaluated by thioflavin T fluorescence, circular dichroism, and ζ-potential measurements. Principal component analysis (PCA) classified the peptides according to their fibril-forming characteristics, and correlation analysis identified the molecular descriptors PCD and IC1 as parameters associated with fibril formation. Cell adhesion assays revealed regions in the PCA distribution associated with enhanced cell adhesion. Based on these relationships, peptides conjugated with non-natural functional groups that were not included in the original peptide library were designed and experimentally evaluated. Several designed peptides exhibited enhanced cell adhesion while retaining fibril-forming properties. In particular, a peptide conjugated with acridine carboxylic acid showed cell adhesion 9-fold higher than that of IAPP(22–27) and 1.7-fold higher than that of gelatin after purification. These results demonstrate that molecular descriptors extracted from a limited experimental peptide dataset enable the rational design of peptides conjugated with non-natural functional groups beyond the original peptide library. The proposed strategy provides a useful framework for developing biomaterials.