| 17 | Relationship between insulin A chain regions and insulin biological activities显示文摘AIM To study the relationship between insulinA chain regions and insulin biological activities,we designed a series of insulin analogues withchanges at A21,A12-18 of C-terminal helicalregion and A8-10 Iocated in the region of A6-A11intra-chain disulphide bond.METHODS Insulin A-chain analogues wereprepared by stepwise Fmoc solid-phase manualsynthesis and then combined with natural B-chain of porcine insulin to yield correspondinginsulin analogues.Their biological activitieswere tested by receptor binding,mouseconvulsion and immunological assay.RESULTS[A21Ala]Ins retains 70.3% receptorbinding capacity and 60% in vivo biologicalactivity.[DesA13-14,A21Ala]Ins and[DesA12-13-14-15,A21Ala]Ins still have definite biologicalactivity,7.9% and 4.0% receptor binding,and6.2% and 3.3% in vivo biological activityrespectively.[A15Asn,A17Pro,A21Ala]Insmaintains 10.4% receptor binding and 10% invivo biological activity.[A8His,A9Arg,A10Pro,A21Ala]Ins,[A8His,A9Lys,A10Pro,A21Ala]Insand [A8His,A9Lys,A10Arg,A21Ala]Ins have51.9%,44.3% and 32.1% receptor bindingrespectively,50%,40% and 30% in vivobiological activity respectively,and 28.8%,29.6% and 15.4% immunological activityrespectively. CONCLUSION A21Asn can be replaced bysimple amino acid residues.The A chains withgradually damaged structural integrity in A12-18helical region and the demolition of the A12-18helical region by the substitution of Pro and Asnfor A17Glu and A15Gln respectively can combinewith the B chain and the combination productsshow definite biological activity,the helicalstructure of A12-18 is essential for biologicalactivities of insulin.A8-10 is not muchconcerned with biological activities,but is muchmore important antigenically in binding to itsantibodies,these results may help us design anew type of insulin analogue molecule. | Yang SZ Huang YD Jie XF Feng YM Niu JY | 2000 | World Journal of Gastroenterology2000，6，3： | 1 |
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