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 ( N γ - Me 2 )- D - L (γ- Me ), and (Bzl) 2 CHCO-VVND-L(γ-Me ) had relative potencies of 110 and 120, respectively, relative to YAGAVVNDL.