Chiral Transformation Of Amino Acid Control Over Adjuvant Activity Of Self-assembling Peptides

The hydrogel is a network crosslinked polymer formed by using water as a medium and physically or chemically crosslinking relatively hydrophilic groups.Because the hydrophilic group inside the network structure can absorb and lock a large number of water molecules,it often has a relatively good water absorption ability,while still maintaining the original three-dimensional network structure.The amino acid is used to synthesize the polypeptide chain and then drive the self-assembly of small molecule hydrogels.In addition to the conventional characteristics of hydrogels,they have better mechanical properties and degradability,with high research value in the fields of biomedical drug delivery,cell culture,and tissue engineering.Immune adjuvant refers to a substance that can enhance the immune response of an organism to an antigen.The good biocompatibility of the peptide self-assembled hydrogel makes it possess the potential to become a new type of immune adjuvant.Substitution of a single amino acid with its enantiomer may lead to variation of self-assembled nanostructures and biological functions.Focus on this problem,in this study,we reported three novel heterochiral peptides hydrogels including Nap-G~DFFY(gel-1),Nap-GF~DFY(gel-2)and Nap-GFF~DY(gel-3)by substitution of a single amino acid with its enantiomer in Nap-GFFY.We found that the resulted hydrogels possessed diverse self-assembly behaviors and adjuvant activities.Compared to homochiral L-gel formed by Nap-GFFY,gel-1 was basically nonchalant,gel-2 exhibited medium improvement in tuning immunocompetence while gel-3 showed better self-assembly nanofibers with superior mechanical properties and slow antigen release ability.Moreover,the adjuvant effect of gel-3 was prominent in promoting both specific antibody titers and production of cytokines.Besides,this regulation was more remarkable in enhancing cellular immune responses.Hence,we came to the conclusion that away from rather than close to end-capping group of substitution of a single amino acid with its enantiomer in this study could be more important and effective to biofunctional regulation.Our study provided a peptide design strategy,by regulating different functional sites of the polypeptide chain,to tune properties of self-assembling hydrogels for different biological applications.