From the RB Tumor Suppressor to MCR Peptides

About twenty years ago, the search for a peptide mimetic of the crucial 928-amino acid human retinoblastoma tumor suppressor protein (RB) has led to the identification of a potential active site in RB spanning 6 amino acids. Subsequent studies revealed that this hexapeptide needs to be coupled to a cellular internalization sequence in order to be biologically active. The prototype molecule resulting therefrom has been the synthetic 22-amino acid peptide MCR-4 that was proven through several investigations to exert both in vitro and in vivo anti-cancer activity both resembling and going beyond the antiproliferative effects of its template RB. This was followed by the elaboration of a distinct series of MCR peptides designed to also interfere with target structures located on the surface of cells and known to be involved in triggering cell proliferation such as the insulin receptor. For this second generation group, the prototype peptide has been another 22-amino acid peptide coined MCR-14 and equally demonstrated to display in vitro and in vivo anti-tumor effects. Finally, a miniaturization of the structure-function relationships intrinsic to the already small MCR-4 peptide has led to the development of the third generation 17-amino acid peptide MCR-15 which in turn was also shown to inhibit in vitro and in vivo malignant cell reproduction. Given more recent conceptual advances, it is warranted to claim that MCR peptides are likely candidate therapeutics not only for the treatment of neoplasias, but also of viral and bacterial infections, type 2 diabetes as well as hypertension.