Table 1. Characteristics of IGF-1 and analogs

IGF-1 analogs listed in Table 1 exhibit altered affinities to the type 1 IGF-1 receptor and IGF-1 binding proteins and can be used to determine their relative importance in regulating the biological activity of IGF-1 [33-36] LongR3IGF-1 is reported to be significantly more potent than native IGF-1, presumably due to the decreased binding of LongR3IGF-1 to all IGF-1 binding proteins, which would normally inhibit the biological actions of IGF-1 [37]. In comparison, the [Ala31]IGF-1 analog has somewhat reduced binding to the IGF-1 receptor, greater affinity for IGF-1 binding proteins, and less stimulation of protein synthesis. The [Leu24][Ala31]IGF-1 analog has undetectable binding to the IGF-1 receptor, but normal binding affinities to IGF-1 binding proteins, and little stimulation of protein synthesis. The [Leu24][Ala31]IGF-1 analog is ideal for investigating IGF-1 actions largely independent of binding to the IGF-1 receptor. With the use of these three analogs in comparison with authentic IGF-1, we tested whether IGF-1-mediated neuroprotective mechanisms depended upon strong interactions between IGF-1 and the IGF-1 receptor or IGF-1 binding proteins. All values expressed as ED₅₀ (ng/ml), the median effective dose (concentration) as determined by interpolation from a dose-effect curve. Data were summarized from product specification sheets provided by GroPep, Ltd. (Adelaide, Australia).

            IGF-1 R1 Affinity for Stimulation

                   IGF-1       Affinity for   Stimulation
  IGF-1 and      Receptor-1   IGF-1 Binding    of Protein
   Analogs        Binding        Proteins      Synthesis
--------------   ----------   -------------   -----------

IGF-1                  5              4             11

LongR3                18          >1000              2

[Ala31]               19              1             38

[Leu24][Ala31]      >750              3          >2000