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Proceedings of the 31 st European Peptide SymposiumMichal Lebl, Morten Meldal, Knud J. Jensen, Thomas Hoeg-Jensen (Editors)European Peptide Society, 2010Peptide FragmentomicsAlexander A. Zamyatnin 1,21 A.N.Bach Institute of Biochemistry, Russian Academy of Sciences, Moscow, 119071,Russian Federation; 2 Universidad Técnica Federico Santa Maria, Departamento deInformática, El Centro Cientifico Tecnologico de Valparaiso, Valparaiso, 1680, ChileIntroductionNatural fragmentation of biological molecules including peptides is well known.Fragmentary structural organization is characteristic of both the simplest and most complexbiological molecules. There are numerous examples showing that relatively small naturalphysiologically active substances are fragments of larger ones. A steady increase in thenumber of publications dealing with protein fragment structure and function has been seenin recent years. For some proteins there are already hundreds of fragments that have beenstudied in detail. Thereupon the term “fragmentomics” is grounded and defined, the basesand determination are given for the notion of the “fragmentome” as a set of all fragments ofa single substance, as well as for global fragmentome of all chemical components of livingorganisms [1,2]. The computer analysis of structure and functions of food proteinfragments was performed in this workResults and discussionThe data of SwissProt database [3] containing primary structures of proteins were used asan object of investigation. Their sequences were compared with EROP-Moscowinformation on structure and functions of regulatory oligopeptides [4] using speciallycreated computer programs [1,2].The input data were the complete amino acid sequences of the proteins used as asource of fragments. The initial sequence was fragmented in a stepwise manner. e.g, in thecase of dipeptide fragments, this procedure produced fragments with the following numbersof amino acids from the N-terminus – 1–2, 2–3, and so on until the fragment that started atthe second residue from the C-terminus. The cases when the amino acid sequence of afragment coincided with the primary structure of a natural oligopeptide were recorded. Thismethod was used to reveal protein regions identical to a regulatory oligopeptide withknown functions. For this theoretical analysis we selected subunits of bovine casein as themost representative in experimental studies.This protein consists of four subunits ( -1s, -2s, , and ) containing from 169 to209 amido acid residues. Amino acid residue composition of -2s and subunits includesall 20 standard amino acid residues, while no cysteine residue is present in subunits -s1and . Computer fragmentation has shown that many small fragments are repeated both ina separate and in different casein subunits. Most frequent were the dipeptide EE fragmentsin subunits -s1, -s2, and . The largest repetitive structures were heptapeptide fragmentsSSSEESI that are present twice in subunit.It can be supposed that the variety of fragmentome structures is the basis for variety ofthe fragment functions. In the case of casein, 60 fragments were obtained experimentallyby different researchers and included in the EROP-Moscow database together withfunctional characteristics. Most of these fragments are enzyme inhibitors (angiotensinconvertingenzyme and cathepsin). The most representative are fragments of -subunit. Aspecial group of four fragments formed of this subunit region (60-70) was namedcasomorphins earlier according to their opioid activity. In the same subunit, the function ofenzyme inhibitors was detected in four fragments of the region 43-66.Computer analysis allowed detection of functional properties in different fragments. Itappeared that 22 different dipeptide and 12 tripeptide casein fragments were fully identicalto natural non-casein oligopeptides obtained from different kingdoms of living organisms.In total, they present 77 regions in all casein subunits and many of them are beyond thelimits of amino acid sequences of experimentally obtained structures. Spectrum of theirfunctions is also diverse. Comparison of data in some cases confirms retention of functionalproperties after fragment shortening. Thus, fragment 31-32 (VF) of -s1 subunit obtainedfrom muscle of S. melanostictus, is a part of fragment 23-34 of the same casein subunit andboth exhibit function of enzyme inhibitor. However, fragment subdivision is accompaniedby alteration of functional properties both in the case of fragment 34-35 (RY) of -subunit32