Development and Comparison of Different Peptide IgG Conjugates for the Treatmentof Gram-Negative Sepsis

摘要

Work over the trimester focused on defining the best LPS binding protein (LBP)peptide sequence, generating peptide-IgO conjugates with this sequence, and assessing the functional ability of these conjugates in buffer and serum. Preliminary work suggested that these, and similar peptides composed of CAPl8 and BPI peptides, lost activity in serum compared to buffer. We compared the bactericidal activity of the LBP peptides in serum and buffer, and assessed the ability of conjugates made with these peptides to bind LPS in serum and buffer. We also evaluated the effect of a terminal cysteine on the peptide on peptide activity. We found that that killing was reduced in serum compared to buffer, and that the ability of the LBP peptide-IgG conjugates to bind radiolabeled LPS was reduced in serum compared to buffer. However, the activity of the peptides was dramatically increased with a terminal cysteine. Experiments using 14C-peptide confirmed previous estimates that constructs contained 3.9 and 9.5 peptides/IgG.