Peptide Sequences and Anti-IL-6 Activity of Key Peptides in the Development of PN-2921.

Subset of residues (position and specific amino acids) mutated on the original ZDC scaffold and key compounds in the development of PN-2729 and its PEGylated analog, PN-2921. All peptides are N-terminally acetylated and all peptides were C-terminal α-amidated except for PN-2519, PN-2729, and PN-2921. Amino acid positions that were randomized by phage display are indicated in bold. IC50 values (n = 2 or more) of peptides in an IL-6 ELISA and an IL-6-induced pSTAT3 assay in U937 cells are shown.ND = not determined.hL = homoleucineCha = cyclohexyl-L-alanineF(4-F) = 4-fluoro-L-phenylalanineKac = Nε-acetyl-L-LysGla = gamma-carboxyglutamic acid.KPEG40Br = 40 kDa branched PEG.Peptide Sequences and Anti-IL-6 Activity of Key Peptides in the Development of PN-2921.