The synthesis of enantiomerically pure, highly functionalized heterocycles: the products of amino acid based acylnitroso hetero Diels-Alder reactions.

The diastereoselectivities of several chiral acylnitroso dienophiles (9a-h, 12 and 15) derived from optically pure, N-protected alpha-amino hydroxamic acids (2a-h, 4 and 7) were determined in an intermolecular hetero Diels-Alder reaction with cyclopentadiene. The diastereomeric excesses ranged from 0 to 72%. Hydroxamic acids with polar functionality were examined extensively to determine the effect of hydrogen bonding on the cycloaddition. The largest increase in diastereoselectivity was observed with increasing the steric bulk at the alpha-position of the hydroxamic acids and not with potential hydrogen bonding interactions. The cycloadditions afforded synthetically useful quantities of functionally rich, enantiomerically pure heterocycles (10a-h, 11a-h, 13, 14, 16 and 17), which have been elaborated into a variety of biologically interesting products.

Peptidomimetic antagonists designed to inhibit the binding of CD4 to HIV GP120.

Attempts to enhance the efficacy of our previously reported CD4 CDR2-like (residues 40-45) mimetic 1 by incorporation of the critical guanidine residue Arg-59 of CD4 are described.

Peptidomimetics of the immunoglobulin supergene family--a review.

An important goal of structural biochemistry is the reduction of complex molecules to small functional units that are amenable to high-resolution structural analysis and rapid modification. The dissection of multidomain proteins into small synthetic conformationally restricted components is an important step in the design of low-molecular-weight nonpeptides that mimic the activity of the native protein. Mimetics of critical functional domains might possess beneficial properties in comparison to the intact proteinaceous species with regard to specificity and therapeutic potential, and are valuable probes for the study of molecular recognition events.