Self‐assembling Peptides with Internal Ionizable Unnatural Amino Acids: A General Approach to pH‐responsive Peptide Materials

Asokan‐Sheeja, Haritha; Yang, Su; Adones, Ashley A.; Chen, Weike; Fulton, Brandon B.; Chintapula, Uday K.; Nguyen, Kytai T.; Lovely, Carl J.; Brautigam, Chad A.; Nam, Kwangho; Dong, He

doi:10.1002/asia.202200724

Self‐assembling Peptides with Internal Ionizable Unnatural Amino Acids: A General Approach to pH‐responsive Peptide Materials

Journal Article · Sat Aug 20 00:00:00 EDT 2022 · Chemistry - An Asian Journal

DOI:https://doi.org/10.1002/asia.202200724· OSTI ID:2423086

Asokan‐Sheeja, Haritha ^[1]; Yang, Su ^[1]; Adones, Ashley A. ^[1]; Chen, Weike ^[1]; Fulton, Brandon B. ^[1]; Chintapula, Uday K. ^[1]; Nguyen, Kytai T. ^[1]; Lovely, Carl J. ^[1]; Brautigam, Chad A. ^[2]; Nam, Kwangho ^[1]; ^[1]

Univ. of Texas, Arlington, TX (United States)
Univ. of Texas Southwestern Medical Center, Dallas, TX (United States)

Self‐assembled peptides are an emerging family of biomaterials that show great promise for a range of biomedical and biotechnological applications. Introducing and tuning the pH‐responsiveness of the assembly is highly desirable for improving their biological activities. Inspired by proteins with internal ionizable residues, we report a simple but effective approach to constructing pH‐responsive peptide assembly containing unnatural ionic amino acids with an aliphatic tertiary amine side chain. Through a combined experimental and computational investigation, we demonstrate that these residues can be accommodated and stabilized within the internal hydrophobic compartment of the peptide assembly. The hydrophobic microenvironment shifts their pK_asignificantly from a basic pH typically found for free amines to a more biologically relevant pH in the weakly acidic range. The pH‐induced ionization and ionization‐dependent self‐assembly and disassembly are thoroughly investigated and correlated with the biological activity of the assembly. This new approach has unique advantages in tuning the pH‐responsiveness of self‐assembled peptides across a large pH range in a complex biological environment. We anticipate the ionizable amino acids developed here can be widely applicable to the synthesis and self‐assembly of many amphiphilic peptides with endowed pH‐responsive properties to enhance their biological activities toward applications ranging from targeted therapeutic delivery to proton transport.

View Accepted Manuscript (DOE)

Research Organization:: Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States). National Energy Research Scientific Computing Center (NERSC)

Sponsoring Organization:: National Institutes of Health (NIH); National Science Foundation (NSF); USDOE; USDOE Office of Science (SC)

Grant/Contract Number:: AC02-05CH11231

OSTI ID:: 2423086

Alternate ID(s):: OSTI ID: 1885088

Journal Information:: Chemistry - An Asian Journal, Journal Name: Chemistry - An Asian Journal Journal Issue: 19 Vol. 17; ISSN 1861-4728

Publisher:: WileyCopyright Statement

Country of Publication:: United States

Language:: English

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37 INORGANIC, ORGANIC, PHYSICAL, AND ANALYTICAL CHEMISTRY
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ionization
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self-assembly
unnatural amino acid

Self‐assembling Peptides with Internal Ionizable Unnatural Amino Acids: A General Approach to pH‐responsive Peptide Materials

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