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The Two Structural Modifications and Their Research Significance Analogues with substitutions, deletions, or insertions at the N-terminal end of native IGF-1 were found to reduce binding to IGFBPs and increase bioavailability to IGF-1R on cells a principle exploited in the design of LR3, where the arginine substitution and N-terminal extension together confer superior IGFBP evasion compared to shorter analogues such as Arg3 IGF-1, Gly3 IGF-1, and Des(1-3) IGF-1