Half-life extension strategies for recombinant protein drugs
Compared with traditional small molecule drugs,recombinant protein drugs have significant advantages,such as higher activity and affinity,and lower toxicity.However,the short plasma half-life caused by factors such as protease degradation,renal elimination,liver metabolism and immune clearance severely limits clinical application of recombinant protein drugs.Therefore,developing corresponding half-life extension strategies is particularly important.Structural modification strategies such as mutants,cyclization,and stapled peptide can increase structural stability of drugs and shield protease recognition sites.Chemical polymer modification represented by polyethylene glycol modification can increase the volume of fluid dynamics of drugs.The natural protein fusion strategy represented by Fc fusion can reduce liver metabolism through corresponding receptor mediated mechanisms.In this paper,we summarize and discuss some classic half-life extension strategies for recombinant protein drugs combined with specific applications,such as structural modification,chemical polymer modification and natural protein fusion.
protein drugsplasma half-lifestructural modificationchemical polymerunstructured polypeptidesglycosylation
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