ABSTRACT

One of the primary barriers of using peptides and proteins as therapeutics is their short half-life in vivo. There are mainly two ways by which peptides and proteins undergo unspecic clearance: either by proteolytic degradation or by kidneymediated ltration. Generally, the circulation times of peptides and proteins can be increased by modifying (derivatizing) the molecules, which guard them from proteolytic degradation or provide molecular weights above the cutoff for kidneymediated clearance (approximately 45 kDa). Typically, such derivatizations include addition of large polymers or molecular motifs that impose binding to native proteins such as albumin. Additionally, such derivatizations have demonstrated protective properties regarding immunogenicity issues, and some types of peptides and protein derivatives have also been applied in targeting specic tissues or organs, such as liver or tumor.