STABILIZED ANALOGS OF THYMOPENTIN .2. 1,2-KETOMETHYLENE AND 3,4-KETOMETHYLENE PSEUDOPEPTIDES

In this second paper in a series of three studies of stable analogs of thymopentin (Arg(1)-Lys(2)-Asp(3)-Val(4)-Tyr(5)) the synthesis of ana logs stablized at peptide bonds 1,2 and 3,4 via insertion of ketomethy lene units is described, A tris(carbobenzyloxy)arginyl(k)norleucine ps eudopeptide was synthesized and coupled to Asp-Val-Phe-resin units fol lowed by HF cleavage to prepare Arg(k)Nle-Asp-Val-Phe analogs. Prepara tion of N-BOC Asp(k)Val and N-BOC Asp(k)Ala units followed by coupling to Phe- or Tyr-resin units provided resin-bound pseudotripeptide subs trates for attachment of various arginyl dipeptides. Cleavage from the resin afforded 3,4-ketomethylene-stabilized pseudopeptide analogs of thymopentin. The Arg-Lys-Asp(k)Val-Phe and Arg-Lys-Asp(k)Val-Tyr analo gs were more strongly bound to CEM cells than thymopentin itself. Ther e was significant enhancement of stability in serum for the analogs, e specially those containing Arg(k)Nle or Arg-NMeLys moieties at the 1,2 -peptide bond.