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-fac -fac -mer -mer0.0 kJ/mol 0.0 kJ/mol 2.1 kJ/mol 2.1 kJ/molFig. 3. Truncated model systems representing the insulin trimers in Figure 2. Thegeometries were obtained at the B3LYP/6-31G(d) level of theory. Relative SCF energiesare given.25-50 nm relative to the measured spectra, the change of sign of the CD signal isreproduced by the calculations in the two characteristic spectral regions (240-350 nm) and(400-700 nm). Since the spectra calculated for and models agree with CDmeasurements for B29 and A1, respectively, the dominating enantiomer in solution hasbeen determined in each case. The calculated spectra for mer and fac configurations areFig. 4. Measured and calculated CD spectra for engineered insulin trimers. Solid blacklines: Measured spectra. Solid grey and dashed black lines: Calculated (RB3LYP/6-31G(d), 100 electronic states) spectra for fac and mer species, respectively. Top panel:Measured CD spectrum for B29 and calculated spectra for fac and mer models. Bottompanel: Measured CD spectrum for A1 and calculated spectra for fac and mer models.nearly identical, and the preference for fac suggested by the relative SCF energies inFigure 3 can therefore not be confirmed from the comparison with measurement. Insummary we have shown from comparison with small model systems that the dominatingenantiomer in solution for the novel insulin trimers is for B29 and for A1. Thestructural basis for the differences in enantioselectivity, as well as mer and fac preferencesare currently under investigation.AcknowledgmentsSupported by NABIIT grant 2106-07-0024 (The Danish Council for Strategic Research).References1. Brange, J., Ribel, U., Hansen, J.F., Dodson, G., Hansen, M.T., Havelund, S., Melberg, S.G., Norris,F., Norris, K., Snel, L., Sørensen, A.R. Nature 333, 679-682 (1988).629