Open AccessInterleukin-17A Peptide Aptamers with an Unexpected Binding Moiety Selected by cDNA Display under Heterogenous Conditions
Author(s) -
Hiroki Anzai,
Takuya Terai,
Kanako WakabayashiNakao,
Tarow Noguchi,
Shigefumi Kumachi,
Masayuki Tsuchiya,
Naoto Nemoto
Publication year - 2021
Publication title -
acs medicinal chemistry letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.065
H-Index - 66
ISSN - 1948-5875
DOI - 10.1021/acsmedchemlett.1c00217
Subject(s) - linker , peptide , context (archaeology) , complementary dna , aptamer , computational biology , cdna library , in vitro , peptide library , chemistry , selection (genetic algorithm) , microbiology and biotechnology , biology , biochemistry , computer science , peptide sequence , gene , paleontology , artificial intelligence , operating system
Peptide-based drugs are an attractive new modality of therapeutics, and in vitro selection from a large-scale library is a powerful way to identify new lead sequences. In conventional screenings, peptide specificity and stability in physiological heterogenous environments are not evaluated, which sometimes makes subsequent optimization difficult. Here we show that selection using a cDNA display system can be performed in a high percentage of serum and that this might be an option to select molecules with high potency and stability in a biological context. Specifically, we chose interleukin-17A as a target protein and performed in vitro selection of cyclic peptide aptamers from a library of approximately 10 12 members in the presence of serum. The selected molecules had nanomolar affinity to the target and were stable in serum. Interestingly, we found that a component of the DNA linker that connected the peptide and cDNA may play a pivotal role in target binding.