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SynopsisPruton magnetic resonaiice data and conformational calcolatioiw of a series of model compounds containing a NH-C"H group substituted as in peptides have been used to generate a proton-proton coupling constant-dihedral angle relation for the peptide unit. For those substances used in which the dihedral angle about the N-C" bond is not fixed, the angle dist,ributiori was calculated from conformational theory. Using eight examples in which the number of theoretical assumpt,ions were least, the best values of the coefficients A, B, and C in the expression J ( e ) = A cosze + H case + C sinZB were found by a least-squares procedure to be 7.9, -1.55, and 1.35, respectively. This relation gives reasonable values for the dihedral angles 6 in cyclir oligopeptide structures for which the availability of both NMR data and other structural information allow comparison. When applied to i\r-acetylamino acid N-methylamides having side chains extending beyond CD, however, agreement with the calculated conformational distribution was found for Leri, Met,, and Trp, but observed values of J were larger t,han expected for Val, Ile, Phe, and Tyr. These disagreements are considered to be the result of interactions not yet taken into account in t.he usual conformational calculations.

SynopsisThe crystal and molecular structure of N-benzyloxycarbonyl-a-aminoisobutyryl-L-prolyl methylamide, the amino terminal dipeptide fragment of alamethicin, has been determined using direct methods. The compound crystallizes in the orthorhombic system with the space group P212~21. Cell dimensions are a = 7.705 A, b = 11.365 A, and c = 21.904 A. The structure has been refined using conventional procedures to a final R factor of 0.054. The molecular structure possesses a 4 -1 intramolecular N-H---0 hydrogen bond formed between the CO group of the urethane moiety and the NH group of the methylamide function.The peptide backbone adopts the type 111 P-turn conformation, with 4 2 = -51.0°, +* = -39.7",An unusual feature is the occurrence of the proline residue a t position 3 of the P-turn. The observed structure supports the view that Aib residues initiate the formation of type 111 @-turn conformations. The pyrrolidine ring is puckered in Cy-exo fashion.

Analysis of X-ray diffraction data from a polycrystalline and well oriented fiber of the sodium salt of poly(dA).poly(dT) shows that this B'-DNA corresponds to a right-handed antiparallel tenfold double-helix of pitch 32.4 A, with C2'-endo furanose rings in both strands. The helix contrasts itself from B-DNA in terms of a very narrow minor groove. Difference electron-density maps have revealed that a continuous spine of water molecules, two per base pair, propagates along this groove with the same symmetry as the DNA and establishes new links between the two strands. In addition to this hydrated DNA helix, the monoclinic unit cell (space group P2(1)) accommodates about 20 sodium ions and 12 water molecules in the vicinity of phosphate groups. These structured guest molecules provide an intricate network of bridges, ranging in size from a single sodium ion to a multiple sodium-water-water-sodium unit, connecting phosphate groups belonging to adjacent DNA helices. The crystallographic R value for this structure is 0.23 for a total of 102 reflections extending out to 3.2 A resolution.

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SynopsisEmpirical energy calculations on cyclo-Gly-X with X = Phe, Tyr, Val, and Leu as a function of the side-chain torsion angles x indicate that the conformations of minimum energy are characterized by x1 = 60°, x2 = 90" for Phe and Tyr, x1 = -60" for Val and x1 = -60°, x2 = 180' and x1 = 60" and xz = 150' for Leu. The minimum energy conformation of cyclo-Gly-Phe and cyclo-Gly-Val have the side chains of Phe and Val stacked over the piperazinedione ring as suggested by NMR and found for cyclo-GlyTyr crystal structure. In contrast, the Leu side chain is expected to exist in an extended or a quasi-folded form.We have recently calculated the energetically favorable conformations of cyclic dipeptides of the type cyclo-Gly-X, with Lamino acid residues X = Phe, Tyr, Val, and Leu. This is of interest in relation to the findings from the NMR studies1+ on cyclo-Gly-Val, cyclo-Gly-Phe, crystal structure studies on ~-Gly-Tyr,~ and molecular orbital calculations on some of these molecule^.^ It is found that the molecules exist preferentially in the folded form shown in Figure 1 for cyclo-Gly-Phe, in which the side chain of Phe or Val is stacked over the piperazinedione ring. This conformation is characterized by an angle of rotation of nearly 60' about the CLY-Ca bond. It may be noted that the peptide units involved are in the cis conformation.We have followed the IUPAC-IUB conventions6 for the description of the conformational parameters. We have calculated the conformational energy as a function of x1 c-Gly-PheThe variation of energy as a function of x1 and x 2 (rotations about CLy-C@ and Ca-C?bonds) for c-Gly-Phe is shown in Figure 2. The c-Gly-Tyr has a very similar energy map.The map has been calculated for x2 in the region 0" to 180' only; the other half is symmetrically related to this by reflection about the line x 2 = 180'. The global minimum occurs near x1 = 60' and x2 = 90'. In this conformation, the aromatic ring folds back about the Cff-C@ bond and stacks over the peptide ring, and there are quite a few nonbonded atoms a t distances close to the sum of the van der Waals' radii for which the nonbonded energy is a minimum. There are two other local minima near (18Oo,6O0) and (-6Oo,l2O0) which are both less stable than the global minimum by about 3 kcal/mole. Consequently the molecule prefers the conformation (6Oo,9O0) in which the rings stack one over the other. These results confirm the observation from NMR studies in which the folded conformation was deduced to be preferred from the upfield shift of the glycyl protons, the direct interaction between the two rings producing an enthalpy change of about 3 kcal/mole.lThe conformation of c-Gly-Tyr in the crystal structure4 has x1 = 55' and x2 = 71', and is marked by a dot in Figure 2. It occurs very near the global minimum calculated by us. The difference between the observed and calculated conformations may be due to packing forces in the crystalline state (the peptide ring in the crystal structure is actually buckled; but a fresh calculation with such a ring d...

Crystals of p-phenylenediamine dihydrochloride are triclinic, a = 8.75, b = 5-87, c = 4-34/~, 0~ = 99°47 ', /~= 95°34 ', 9,= 111 o 10', Z= 1, space group Pi'. The structure has been determined in two projections. Three-dimensional X-ray intensity data were used to refine the positional and thermal parameters c the atoms by the least-squares method. All the hydrogen atoms in the molecule were located from an (Fo-Fc) synthesis; the final R value is 0.106. The molecules in the lattice are held together by a system of hydrogen bonds of the type N-H. • • CI-. The C-NH + bond length of 1.49/~ in this structure is very close to the mean value of 1.487/~ observed in accurately determined structures of ~-amino acids.

The molecular structure of nucleoprotamine from Gibbula divaricata and its packing in oriented fibers has been modelled both to fit the X-ray diffraction pattern and to avoid steric compression. The representative model consists of 51 poly (dinucleotide) B-DNA helices with 51 poly(hexapeptide) chains associated with the major grooves. The prevailing peptide conformation is beta. The four arginine residues present are hydrogen-bonded to DNA phosphates while neutral peptides protrude into the minor grooves of neighboring nucleoprotamine molecules which are packed 2.61 nm apart in a screw-disordered, quasi-hexagonal lattice. This model reconciles a number of earlier, apparently conflicting experimental results and explains the remarkable stability of nucleoprotamines.