Clinical targeting of HIV capsid protein with a long-acting small molecule.

Oral antiretroviral agents provide life-saving treatments for millions of people living with HIV, and can prevent new infections via pre-exposure prophylaxis. However, some people living with HIV who are heavily treatment-experienced have limited or no treatment options, owing to multidrug resistance. In addition, suboptimal adherence to oral daily regimens can negatively affect the outcome of treatment-which contributes to virologic failure, resistance generation and viral transmission-as well as of pre-exposure prophylaxis, leading to new infections.

Theoretical study of the stereoselective additions of chiral alcohols to ketenes.

In 1989, Larsen et al. at Merck discovered that the addition of chiral alcohols to ketenes provided enantiomerically enriched aryl propionic acids, compounds valued for their therapeutic antiinflammatory properties. The high 1,4-asymmetric induction observed (>99:1 dr in the addition, and up to 99% ee after hydrolysis to the acid) is rare.

Experimental determination of the absolute enantioselectivity of an antibody-catalyzed Diels-Alder reaction and theoretical explorations of the origins of stereoselectivity.

The exo and endo Diels-Alder adducts of p-methoxycarbonylbenzyl trans-1,3-butadiene-1-carbamate and N,N-dimethylacrylamide have been synthesized, and the absolute configurations of resolved enantiomers have been determined. On the basis of this information, the absolute enantioselectivities of the Diels-Alder reaction catalyzed by antibodies 13G5 and 4D5 as well as other catalytic antibodies elicited in the same immunizations have been established. The effects of different arrangements of catalytic residues on the structure and energetics of the possible Diels-Alder transition states were modeled quantum mechanically at the B3LYP/6-311++G**//B3LYP/6-31+G** level of theory.

Magnitudes and chemical consequences of R(3)N(+)-C-H...O[double bond]C hydrogen bonding.

The magnitude of the stabilizing interaction between an aliphatic C[bond]H bond attached to an ammonium nitrogen and a carbonyl oxygen was evaluated by ab initio calculations at the MP2/6-311++G** level of theory. Attractive R(3)N(+)-C-H..