Rapid replication and Replikintm structures: basis of the AMASRTest and CAVAXR.

Samuel Bogoch and Elenore S. Bogoch

Foundation for Research on the Nervous System and Oncolab, 36 The Fenway, Boston MA 02215, USA

Antimalignin antibody in serum (AMAS) is elevated in early malignancy, is cytotoxic to cancer cells at picograms/cell, and relates quantitatively to survival in cancer patients, all regardless of cell type (J.Cell Biochem19:172-185,1994;Cancer Letters148:39-48,2000). Rapid replication is characteristic of virulence in certain bacteria, viruses and malignancies, but no chemistry common to rapid replication in different organisms has been described. We now have found a new family of small peptides related to this phenomenon, here called Replikins, which offer discrete new targets for detection and therapy. The prototype for Replikins is the cancer cell peptide malignin which we found to be enriched ten-fold during five-fold more rapid anaerobic replication of glioblastome multiforme (glioma) cells. Hydrolysis and mass spectrometry of malignin revealed a 16 mer peptide sequence. A recognition proteomic system has been constructed specifying the requirements for designation of the Replikin structure as a homologue of this peptide sequence. We examined visually over 3,000 protein sequences for homologues. Homologues were found infrequently in large protein populations, e.g. in only 1.5% of Pubmed "virus peptides"(N=953), and 8.5% of "neuropeptides" plus "brain peptides"(N=845). However, surprisingly homologues were frequent in large "replicating proteins", so-named by their investigators because of the proteins' established replicating function in algae, bacteria and viruses; and remarkably, homologues occured in 100% of "tumor viruses"(N=250), in 97% of "cancer proteins"(N=401), and in 85% of "transforming proteins"(N=248). The implications are suggestive for cancer pathogenesis. Also, safer synthetic vaccines against cancer (CAVAXR) and perhaps against other Replikin-containing organisms are now possible.

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Paper presented at the International Symposium on Predictive Oncology and Intervention Strategies; Paris, France; February 9 - 12, 2002; in the section on Prevention.