A pentacosapeptide (CKS-25) homologous to retroviral envelope proteins possesses a transforming growth factor-β activity

Abstract

CKS-17, a synthetic heptadecapeptide homologous to a conserved domain in retroviral envelope protein p15E, mimics the immunosuppressive properties of p15E in vitro and in vivo, but the mechanisms are not understood. Here we report that a synthetic pentacosapeptide designated CKS-25, a longer version of CKS-17 that contains a functional transforming growth factor-β3 (TGF β3) active-site motif (RXXD), inhibits 125I-labeled TGF-β1 (125I- TGF-β1) binding to cell-surface TGF-β receptors in cultured epithelial cells. Multiple conjugation of CKS-25 to bovine serum albumin and carbonic anhydrase enhances the 125I-TGF-β1 binding inhibitory activity and confers a partial TGF-β agonist activity (growth inhibition but not transcriptional activation). Since TGF-β is a potent immunosuppressive factor, these results suggest that the immunosuppressive properties of CKS- 17-bovine serum albumin conjugate and p15E are mediated at least in part by their TGF-β agonist activities.