Title:From the RB Tumor Suppressor to MCR Peptides
Volume: 21
Issue: 6
Author(s): Razvan T. Radulescu
Affiliation:
Keywords:
Bacterial infection, bioinformatics, cancer, diabetes, drug design, hypertension, oncology, pharmacology, retinoblastoma
tumor suppressor protein (RB), synthetic peptides, therapeutics.
Abstract: 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.
