Vladimir Khavinson1, Larisa Shataeva, Anna Chernova. 1. St.Petersburg Institute of Bioregulation and Gerontology, North-Western Branch of the Russian Academy of Medical Science, 3, Dynamo Prospect, St-Petersburg, 197110, Russia. khavinson@gerontology.ru
Abstract
PROBLEM: Gerontology observations show that ageing of organism is accompanied by the decrease of the chromatin activity and slowing down of the protein synthesis. Natural regulatory oligopeptides and their synthetic analogues take part in the activation of chromatin and normalise rate of the protein synthesis in cultured tissues. Regulatory peptides significantly enhance longevity. OBJECTIVES: The objective of this work is to find a possible molecular mechanism by which the regulatory peptides influence the part of genetic system is responsible for initiation of protein synthesis in higher organisms. METHODS: An interdisciplinary approach was used to address the problem. The work involved not only medical scientists and biologists, but also specialists in biopolymer chemistry, and mathematicians for statistical analysis of information interaction of amino acid and nucleotide sequences. CONCLUSIONS: The structures and metrics of peptides and the DNA double-helix cause the recognition and complementary binding of a regulatory peptide with DNA functional groups at the interface of the major groove. We have used complementary binding model to find a possible base pair sequence ATTTTC for specific binding of synthetic tetrapeptide epitalon. This base pair block and its reverse complement were found repeatedly in the promoter region of telomerase. A comparison of statistical information content of peptides and oligonucleotide sequences shows that these two classes of biopolymers are information carriers and. exchange the information to initiate the gene transcription.
PROBLEM: Gerontology observations show that ageing of organism is accompanied by the decrease of the chromatin activity and slowing down of the protein synthesis. Natural regulatory oligopeptides and their synthetic analogues take part in the activation of chromatin and normalise rate of the protein synthesis in cultured tissues. Regulatory peptides significantly enhance longevity. OBJECTIVES: The objective of this work is to find a possible molecular mechanism by which the regulatory peptides influence the part of genetic system is responsible for initiation of protein synthesis in higher organisms. METHODS: An interdisciplinary approach was used to address the problem. The work involved not only medical scientists and biologists, but also specialists in biopolymer chemistry, and mathematicians for statistical analysis of information interaction of amino acid and nucleotide sequences. CONCLUSIONS: The structures and metrics of peptides and the DNA double-helix cause the recognition and complementary binding of a regulatory peptide with DNA functional groups at the interface of the major groove. We have used complementary binding model to find a possible base pair sequence ATTTTC for specific binding of synthetic tetrapeptide epitalon. This base pair block and its reverse complement were found repeatedly in the promoter region of telomerase. A comparison of statistical information content of peptides and oligonucleotide sequences shows that these two classes of biopolymers are information carriers and. exchange the information to initiate the gene transcription.