| abstract |
To reduce the affinity for serum proteins so as to enable good activity in the presence of serum while maintaining sufficient affinity for cell membranes to be transported into the cell Cross-linked polypeptides and methods for optimization that maintain sufficient affinity for serum proteins to have possible pharmacokinetics and retain high affinity binding to the intracellular target receptor (s). Biologically active cross-linked polypeptides, and methods for identifying and making the improved polypeptides. In one embodiment, a method for identifying a cross-linked polypeptide with improved efficacy in human whole blood comprises synthesizing an analog of the parent cross-linked polypeptide and in the absence of human serum proteins and one or more. Carrying out a cellular assay in the presence of human serum at a concentration of thereby determining the apparent affinity of each cross-linked polypeptide for human serum proteins. [Selection figure] None |