Abstract
The functionally important regions of signal proteins participating in their specific interaction and responsible for transduction of hormonal signal into cell are rather short in length, having, as a rule, 8 to 20 amino acid residues. Synthetic peptides corresponding to these regions are able to mimic the activated form of full-size signal protein and to trigger signaling cascades in the absence of hormonal stimulus. They modulate protein-protein interaction and influence the activity of signal proteins followed by changes in their regulatory and catalytic sites. The present review is devoted to the achievements and perspectives of the study of signal protein-derived peptides and to their application as selective and effective regulators of hormonal signaling systems in vitro and in vivo. Attention is focused on the structure, biological activity, and molecular mechanisms of action of peptides, derivatives of the receptors, G protein α subunits, and the enzymes generating second messengers.
Highlights
The transduction of signals generated by hormones and hormone-like substances of different nature to intracellular effector proteins controlling the fundamental cellular processes requires coordinated activity of many signal proteins, components of a wide spectrum of G protein-coupled and G protein-independent signaling systems, and has several steps in common
The length of biologically active signal protein-derived peptides does not usually precede 15–20 amino acid residues, and they can be synthesized in a short time and in quantum satis, using the solid-phase method, purified to homogeneity by reversed phase HPLC and characterized by massspectrometry, amino acid analysis, and other appropriate methods
To enhance biological activity and selectivity of the action of peptides and to obtain their analogs with higher stability to hydrolytic enzymes, signal protein-derived peptides are subjected to different modifications, such as selective blocking of free functional groups of amino acids, substitution of L- by D-amino acids and of natural amino acids by rare, nonnatural, amino acids, synthesis of cyclic and branched forms of peptides and their di- and oligomeric constrains, and attachment to them of hydrophobic radicals
Summary
The transduction of signals generated by hormones and hormone-like substances of different nature to intracellular effector proteins controlling the fundamental cellular processes requires coordinated activity of many signal proteins, components of a wide spectrum of G protein-coupled and G protein-independent signaling systems, and has several steps in common. It is not unexpected that the synthetic peptides corresponding to these regions are able to trigger signaling cascades in the absence of hormonal stimulus, modulate protein-protein interaction, and influence the functional activity of signal proteins induced due to changes in their regulatory and catalytic sites. They have been used as important tools in mimicking functional domains of signal proteins, the component of hormonal signaling systems. The present review is devoted to the achievements and perspectives of the study of hormonal signaling systems described in terms of the peptide strategy, a new perspective approach of biochemistry and molecular endocrinology, based on application of synthetic peptides as probes corresponding to functionally important regions of signal proteins, such as receptors of different nature, heterotrimeric G proteins, and the enzymes generating second messengers and responsible for appropriate response of the cell to external signal
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