CENTROSYMMETRIC CRYSTALS OF A DESIGNED, ALPHA-HELICAL PEPTIDE.

E1086

CENTROSYMMETRIC CRYSTALS OF A DESIGNED, ALPHA-HELICAL PEPTIDE. William R. Patterson and David Eisenberg, UCLA-DOE Laboratory of Structural Biology and Molecular Medicine and Department of Chemistry and Biochemistry, University of California, Los Angeles, California.

We are exploring the packing interactions of de novo designed, alpha-helical peptides in racemic mixtures for use as novel biomaterials. Crystals of the 12-residue peptide, [[alpha]]-1, were produced by vapor diffusion methods in the presence of both peptide enantiomers. X-ray diffraction data were collected at 92 K and were 87% complete to 2.1 Å with a scaling R-factor of 13.7%. The crystals indexed initially in space group P1 with a=20.79 Å, b=20.35 Å, c=27.95 Å, [[alpha]]=101.48^o, [[beta]]=97.77^o, and [[gamma]]=120.88^o. However, these unit cell parameters are nearly identical to the P1 unit cell of the L-[[alpha]]-1 enantiomer. To test for the presence of inversion symmetry, a cumulative intensity distribution was calculated for the D,L-[[alpha]]-1 and L-[[alpha]]-1 intensity data (Table 1). The intensity distributions show that the putative, racemic data follow the theoretical centric distribution while the L-[[alpha]]-1 data follow the theoretical acentric distribution. We conclude that the crystals are centrosymmetric and belong to space group P1bar, with 2 peptides in the asymmetric unit. Currently, we are optimizing the racemic crystallization condition to produce larger crystals in an effort to obtain higher resolution data for use with direct methods techniques.

Table 1. Cumulative intensity distribution. Z = I/<I>, and N(Z) is the number of reflections, in bins of increasing resolution, which correspond to a given Z value.

                     N(Z)                                   
Z       Acentric     L-[[alpha]]  Centric       D,L-[[alph  
                     -1                         a]]-1       
        Theoretical  Observed     Theoretical   Observed    
0.0     0.0          0.0          0.0           0.0         
0.1     9.5          9.7          24.8          25.4        
0.2     18.1         20.1         34.5          35.8        
0.3     25.9         29.0         41.6          44.2        
0.4     33.0         36.3         47.3          50.2        
0.5     39.3         42.9         52.1          55.4        
0.6     45.1         48.8         56.1          60.4        
0.7     50.3         53.8         59.7          64.2        
0.8     55.1         58.4         62.9          67.2        
0.9     59.3         62.1         65.7          69.8        
1.0     63.2         65.7         68.3          72.8