Method to generate highly stable D-amino acid analogs of bioactive helical peptides using a mirror image of the entire PDB.

ABSTRACT: Biologics are a rapidly growing class of therapeutics with many advantages over traditional small molecule drugs. A major obstacle to their development is that proteins and peptides are easily destroyed by proteases and, thus, typically have prohibitively short half-lives in human gut, plasma, and cells. One of the most effective ways to prevent degradation is to engineer analogs from dextrorotary (D)-amino acids, with up to 10⁵-fold improvements in potency reported. We here propose a general peptide-engineering platform that overcomes limitations of previous methods. By creating a mirror image of every structure in the Protein Data Bank (PDB), we generate a database of ∼2.8 million D-peptides. To obtain a D-analog of a given peptide, we search the (D)-PDB for similar configurat

SUBMITTER: Garton M 

PROVIDER: S-EPMC5816147 | biostudies-literature | 2018 Feb

REPOSITORIES: biostudies-literature