John Hannah

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.

Noncovalent Binding of a Spin-Labeled Inhibitor to Ribonuclease

The stable free radical 2,2,6, 6-tetramethyl-4-hydroxypiperidin-1-oxyl monophosphate has been synthesized; it binds to ribonuclease. The selective changes in the nuclear magnetic resonance spectrum of the enzyme produced by the free radical make it possible to define qualitatively the region of the enzyme to which it binds. The radical appears to occupy a site similar to that to which inorganic phosphate binds which is close to or within the active site of the enzyme.

Substituted penta- and hexapeptides as potent inhibitors of herpes simplex virus type 2 ribonucleotide reductase

Abstract Structural modifications of the Tyr, Asn, and Leu residues of YVVNDL, a peptide which is equipotent to YAGAVVNDL in the inhibition of herpes simplex virus type 2 ribonucleotide reductase (HSV-2 RR), have produced peptides which are as much as 90- to 120-times as potent as YAGAVVNDL in vitro against HSV-2 RR. The chemistry and the structure activity relationships of these inhibitors are described. For the inhibition of herpes simplex virus type 2 ribonucleotide reductase (HSV-2 RR), structure-activity relationship studies on Y, N, and/or L of YVVNDL (equipotent to YAGAVVNDL on HSV-2 RR) using synthetic peptides are reported. The most potent of these, YVV-N(Nγ-Me2)-D-L(γ-Me), and (Bzl)2CHCO-VVND-L(γ-Me) had relative potencies of 110 and 120, respectively, relative to YAGAVVNDL.

Muramyl peptide analogs : Synthesis of a depsipeptide using orthogonal SPPS

Abstract A depsipeptide mimic of the Gram-positive muramyl peptide was synthesized on resin using both Boc and Fmoc protection strategies. The depsipeptide unit is chemically and stereochemically compatible with both Boc and Fmoc chemistries and with HF cleavage conditions.