The thermal racemization of optically active allyl sulfoxides has been shown on the basis of kinetic evidence and labeling experiments to proceed by way of a facile, reversible, and wholly concerted rearrangement to optically inactive allyl sulfenates. The reaction involves an intramolecular cyclic a,y shift of the allyl group between the sulfoxide oxygen and sulfur termini. Rearrangement of (S)-a-methylallyl p-toluenesulfenate to (5)frnns-crotyl p-tolyl sulfoxide proceeds with at least 37 % stereospecificity and provides an example of an asymmetric synthesis in which one chiral center (sulfur) is generated at the expense of another (carbon).

Three-dimensional computer models for two segments of the C terminus of gp41, the transmembrane AIDS envelope protein, which may form amphipathic alpha-helices, have been generated using structure prediction techniques combined with energy minimization and molecular dynamics simulations. Regions gp41(772-790) and gp41(828-848) of the HXB2 strain of HIV-1 display extraordinarily high hydrophobic moment maxima as alpha-helices and when in an antiparallel conformation exhibit charge complementarity, implying that they may bind with each other and associate with the membrane. The feasibility of this hypothesis was tested in a series of computer simulations of these peptides, extended by several residues to include additional charge pairing. Beginning with a trial structure in the form of antiparallel alpha-helices of segments 770-794 and 824-856, systematic axial rotations and displacements were used to generate alternative initial states. Molecular dynamics simulations with alpha-helical torsional restraints yielded several approximately cylindrical dimeric structures highly stabilized by numerous salt links and other hydrogen bonds. This suggests that these two regions may fold back on each other in antiparallel fashion to form a loop in the tertiary structure over residues 770-856, with the loop closed by membrane-associated amphipathic alpha-helices with charged sides facing each other. We speculate that such structures could aggregate to form channels or otherwise destabilize the membrane, thereby contributing to the cytopathic effects of the gp120-gp41 complex.

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60) Since V, is oriented perpendicular to the Fe-N4 plane in 20, the same orientation might be expected in 19. The observation of preferential ori-(1967).(62) M. M.'Maltempo. Electronic spectra are not informative in this respect due to the spin-forbidden nature of ligand field transitions and the intense charge-transfer and ligand-based absorptions throughout the uv-visible region. Spectral Abstract: Cobalt(II1) carboxypeptidase A has been prepared by the oxidation of cobalt(I1) carboxypeptidase A with hydrogen peroxide at pH 7.5. The oxidized enzyme shows negligible peptidase activity after dialysis against metal-free buffer or 1, IO-phenanthroline while its esterase activity toward hippuryl-L-0-phenyllactate and trans-p-nitrocinnamoyl-L-&phenyllactate is comparable to that of cobalt(I1) carboxypeptidase A. Carbobenzyloxyglycyl-L-phenylalanine, toward which the cobalt(I1) enzyme is active, competitively inhibits the activity of the cobalt(II1) protein toward hippuryl-D,L-p-phenyllactate. The metal in the oxidized enzyme is no longer removable by dialysis against metal-free buffer, but may be reduced back to cobalt(I1) and exchanged by dialysis against excess cobalt(I1). Cobalt(iI1) carboxypeptidase A has a visible absorption maximum at 503 nm (t 500). The pH dependence of ester hydrolysis by cobalt(II1) carboxypeptidase A shows that catalysis requires the basic form of a group on the enzyme with pKa 6.3-6.5 and the acidic form of a group with pK, 9.1-9.5. These results have a bearing on the mechanism of action of carboxypeptidase A. In particular, they imply that the group of higher pK, is not a water molecule bound to the metal and that ligation of substrates within the first coordination sphere of the metal does not occur during ester hydrolysis catalyzed by cobalt(II1) carboxypeptidase A.

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