What to synthesize? from Emil Fischer to peptidomics

Abstract

The driving forces, incentives and strategic targets of peptide synthesis have undergone considerable evolution during the centenary following the pioneer work of Emil Fischer. In those days peptide synthesis was considered as a way of confirming the polypeptide theory of protein structure. The scientific community also expected (naively) that the synthesis would eventually lead to the creation of artificial living organisms. Only in the 1950s, when the first exact amino acid sequences were established did peptide chemistry obtain firmer ground and clearly defined targets. The total synthesis of peptide hormones and antibiotics became possible, providing valuable material for elucidating structure-functional relationships and the mechanisms of biological action. In the following years the number of peptides isolated from various biological sources grew with impressive speed and peptides became known as the most abundant, ubiquitous group of low molecular bioregulators. The design and synthesis of novel peptide based pharmaceuticals became an important area of peptide chemistry. At present we are facing the challenge of analysing the structures and bioactivities of total sets of peptides, i.e. peptidoms, present in concrete tissues or groups of cells. The results obtained along these lines at the IBCH RAS Institute of Bioorganic Chemistry are briefly considered in the review.

Stimulation of fibroblast proliferation by neokyotorphin requires Ca2+ influx and activation of PKA, CaMK II and MAPK/ERK

“…In other words, cAMP‐dependent signaling results in cell‐ and/or tissue‐specific reactions, contributing to the maintenance of tissue homeostasis. Previously, we postulated that components of tissue‐specific peptides pools, of which neokyotorphin is a frequently found example, are also involved in the regulation of tissue homeostasis [4]. We have shown that the release of neokyotorphin by erythrocytes is an active and energy‐dependent process [54], which confirms its physiological importance.…”

“…Neokyotorphin, α‐globin segment (137–141), was initially isolated from bovine brain and characterized as an analgesic peptide [1], the effect of which is not associated with binding of the peptide to any membrane receptor [2,3]. We have previously shown that neokyotorphin, along with a number of other functional protein fragments [4], is present in a variety of mammalian tissues [5] and is secreted by human erythrocytes [6]. The proliferative activity of neokyotorphin in normal and tumor cells has been widely reported [7–9].…”

The Future of Post-Genomic Biology at the Proteomic Level: An Outlook

“…Progress in peptide separation techniques is moving fast [33] and sequential separation steps become more and more integrated into multidimensional analytical processes directly coupled to mass-spectrometric analysis [34]. The driving force for these developments is undoubtedly related to the fact that peptides are known as the most abundant, ubiquitous group of low mass molecular bioregulators accessible to chemical synthesis [35]. Therefore, molecular information about this class of molecules opens the possibility for the de novo design and synthesis of novel peptide-based pharmaceuticals.…”

Получение И Оценка Биологических Свойств Низкомолекулярного Пептидного Комплекса, Выделенного Из Эритромассы Крови Человека

“…Òàêèå âåùåñòâà íîñÿò íàçâàíèå ãåìîðôèíû -ýíäîãåííûå ðåãóëÿòîðíûå ïåïòèäû ãåìîãëîáèíà; îáëàäàþò ñâîéñòâàìè, ñõîäíûìè ñ àíãèîòåíçèíàìè (â òîì ÷èñëå â îòíîøåíèè óñêîðåíèÿ ðåïàðàöèîííûõ ïðîöåññîâ â ïîâðåaeäåííûõ òêàíÿõ) [4,5]. Ïðè èññëåäîâàíèè ñâîéñòâ ãåìîðôèíîâ âûÿâëåíî, ÷òî äëÿ íèõ õàðàêòåðíà âûñîêàÿ öèòîòîê-ñè÷íîñòü è àíòèïðîëèôåðàòèâíàÿ àêòèâíîñòü ïî îòíîøåíèþ ê îïóõîëåâûì êëåòêàì [6]; ïðè ýòîì ãåìîðôèíû íåòîêñè÷íû è îáëàäàþò ïðîëèôåðàòèâíîé àêòèâíîñòüþ ïî îòíîøåíèþ ê íîðìàëüíûì êëåòêàì [7].…”