William J. Leanza

An efficient synthesis of 2-substituted-thio-6-hydroxyethyl-penem-3-carboxylic acids via 2-thioxopenams

Abstract Allyl and p -nitrobenzyl (5R, 6S)-6-[(R)-1-(t-butyldimethylsilyloxy)ethyl]-2-thioxopenam-3-carboxylates ( 19 ) were synthesized by base mediated cyclization of the corresponding 1-carboxylmethyl-4-phenoxy (thiocarbonyl)thio-2-azetidinones ( 16 ). The thioxopenams underwent alkylation and Michael reactions to produce 2-alkylthio- and 2-alkenylthio-penem derivatives 20 and 21 .

Immunogenicity of synthetic HIV-1 gp120 V3-loop peptide-conjugate immunogens.

A successful prophylactic human immunodeficiency virus type 1 (HIV-1) vaccine must elicit an immune response that will prevent establishment of the persistent viral infection. The only response shown to be effective in this regard is virus-neutralizing antibody directed against the viral gp120 hypervariable V3-loop region. Conjugate immunogens, containing cyclic peptides representing the V3 determinant covalently bound to a carrier protein, were capable of eliciting virus-neutralizing antibodies. The consistency of the response was related to peptide size. The smaller cyclic peptides, expressing relatively conserved sequences from the V3-loop apex, were poor inducers of neutralizing activity. In contrast, the largest cyclic peptides mediated neutralizing responses that were similar to those observed and previously reported for intact gp120 immunogens. A cyclic synthetic peptide expressing most of the prototypic HIV-1 MN variant V3 determinant warrants further study as a potentially effective vaccine immunogen.