Design of a novel thymopoietin analogue based on conformational analyses.

ABSTRACT

A novel cyclic peptide c(Arg-Pro-Asp-D-Val-Tyr) related to thymopentin--the immunostimulant pentapeptide contained in thymic hormones--was designed on the basis of theoretical computer modeling. We applied molecular dynamics/energy minimization techniques and restrained molecular dynamics to determine the preferred conformation of this peptide. The linear precursor of the peptide is biologically active and probably exists in a highly motile dynamical equilibrium of different conformations. Our calculations show that the cyclic peptide consists of a single conformational family containing a beta turn at position Pro 2. Experimental support for this conclusion was derived from 2-D NOE data in aqueous solution for the closely related analogue c(Arg-Lys-Glu-D-Val-Tyr). Synthesis and biological testing of the cyclic peptide is therefore indicated.