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Two Chain "Insulin/Insulin-like Growth Factor-I" Hybrids
Yue-Hua Tang1, Heng-Ran Cui, You-Min Feng
1State Key Laboratory of Molecular Biology, Shanghai Institute of Biochemistry, Academia Sinica, Shanghai 200031, China.
Sheng Wu Hua Xue Yu Sheng Wu Wu Li Xue Bao Acta Biochimica Et Biophysica Sinica
|January 1, 1996
Summary
Researchers created novel insulin-like growth factor-I (IGF-I) hybrid molecules. These hybrids demonstrated full insulin activity in vivo, indicating modifications do not impact insulin function.
Area of Science:
- Biochemistry
- Molecular Biology
- Endocrinology
Background:
- Insulin and Insulin-like Growth Factor-I (IGF-I) are crucial peptide hormones involved in metabolic regulation and growth.
- Understanding the structure-activity relationship of these hormones is key to developing novel therapeutic agents.
Purpose of the Study:
- To synthesize and characterize novel hybrid molecules combining insulin and IGF-I sequences.
- To evaluate the in vivo biological activity of these hybrid molecules compared to native insulin.
Main Methods:
- Enzymatic semisynthesis was employed to create two-chain "Insulin/Insulin-like Growth Factor-I" hybrids: Ins/IGF-I(8) and Ins/IGF-I(11).
- Desoctapeptide insulin (DOI) was used as a starting material, along with chemically synthesized octapeptide and undecapeptide fragments of IGF-I (sequences 22-29 and 22-32).
Main Results:
- The synthesized hybrid molecules, Ins/IGF-I(8) and Ins/IGF-I(11), were successfully obtained.
- In vivo studies demonstrated that these hybrid molecules retain the full biological activity of native insulin.
- Specific modifications, including amino acid substitutions (B27Thr to Asn, B30Ala to Thr), altered sequence orders (B25/B26, B28/B29), and B30 tripeptide extension (Gly-Tyr-Gly), did not diminish insulin activity.
Conclusions:
- The study successfully generated novel insulin-IGF-I hybrid molecules.
- These findings indicate that significant modifications to the insulin B-chain, including substitutions and extensions, can be tolerated without loss of insulin activity.
- This research provides insights into the structural determinants of insulin's biological function and opens avenues for protein engineering in endocrinology.