Why peptides are cleared fast
Peptidases in blood and tissue cleave peptide bonds. Small peptides are also filtered by the kidney. Together these give many native sequences a half-life measured in minutes.
Modifications that extend it
- Substituting residues at cleavage sites so proteases no longer recognise them
- Acylation with a fatty acid chain, promoting albumin binding
- Attachment of polyethylene glycol, increasing effective size above the filtration threshold
- Cyclisation or non-natural residues, which proteases handle poorly
- N-terminal extensions that reduce binding-protein affinity, as in IGF-1 LR3
Reading half-life figures
A half-life is specific to a species, a route and a measurement method. Values from rodent studies do not transfer to other species, and in vitro stability in plasma is a different measurement again. A figure without its context is not usable.
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