title: [Regulation of adenylyl cyclase activity in the rat testes by acylated derivatives of peptide 562-572 of luteinizing hormone receptor].
abstract: One of directions of the search of hormonal signaling systems regulators is the development of peptides that correspond to the cytoplasmic regions of G-protein-coupled receptors (GPCR). Modification of the pepti- des with hydrophobic radicals increases their efficiency and selectivity. But currently is not studied as the acti- vity of the peptide depends on the localization of the hydrophobic radicals, their number and the chemical natu- re. The aim of this work was the synthesis of modified by fatty acid radicals derivatives of peptide 562-572 corresponding to the C-terminal region of luteinizing hormone receptor (LHR), and the study of regulatory ef- fects of the acylated LHR-peptides on the basal and hormone-stimulated activity of adenylyl cyclase (AC) in the rat tissues. To elucidate the effect of localization of hydrophobic radicals and their number the modification of peptide 562-572 only at the N- or C-terminus or at both ends was carried out. To study the effect of hydrop- hobicity the residues ofpalmitic (Pal) and decanoic (Dec) acids were selected. Using a solid phase strategy we have synthesized unmodified peptide NDTKIAKK-Nle-A562-572-KA (1) and five of its acylated analogues, such as N[K(Dec)]DTKIAKK-Nle-A562-572-KA (2), NKDTKIAKK-Nle-A562-572-[K(Dec)]A (3), N[K(Dec)] DTKIAKK-Nle-A562-572-[K(Dec)]A (4), N[K(Pal)]DTKIAKK-Nle-A562-572-KA (5), and NKDTKIAKK-Nle- A562--572-[K(Pal)]A (6). Peptide 6 modified with palmitate at the C-terminus to a large extent increased the ba- sal AC activity and reduced AC stimulating effect of human chorionic gonadotropin (hCG) in the testes of rats, peptides 3 and 4 modified with decanoate at the C-terminus were less effective, but exceeded in activity the un- modified peptide 1, while peptides 2 and 5 acylated at the N-terminus were little active. The action of peptides was characterized by the tissue and the receptor specificity. Thus, the modification of LHR-peptide 562-572 with fatty acid radicals at the C-terminus increases its regulatory effect on the functional activity of the adenyla- te cyclase system in the rat testes, indicating promising the modification of GPCR-peptides with hydrophobic radicals. These data support the hypothesis that the hydrophobic radical to be localized in the locus of GPCR-peptide, where a transmembrane domain is located in the receptor.
authors.forename: E A
authors.initials: EA
authors.lastname: Shpakova
authors.forename: A O
authors.initials: AO
authors.lastname: Shpakov
mesh_terms: D000067956:Adenylyl Cyclase Inhibitors; D000262:Adenylyl Cyclases / Q000378:metabolism*; D000595:Amino Acid Sequence; D000818:Animals; D002458:Cell Fractionation; D002462:Cell Membrane / Q000187:drug effects* / Q000201:enzymology; D006063:Chorionic Gonadotropin / Q000494:pharmacology; D003652:Decanoic Acids / Q000737:chemistry; D004789:Enzyme Activation / Q000187:drug effects; D006801:Humans; D057927:Hydrophobic and Hydrophilic Interactions; D008297:Male; D008969:Molecular Sequence Data; D009842:Oligopeptides / Q000138:chemical synthesis / Q000737:chemistry / Q000494:pharmacology*; D019308:Palmitic Acid / Q000737:chemistry; D017434:Protein Structure, Tertiary; D051381:Rats; D011974:Receptors, LH / Q000737:chemistry*; D060327:Solid-Phase Synthesis Techniques; D013329:Structure-Activity Relationship; D013737:Testis / Q000187:drug effects* / Q000201:enzymology
chemical_list: D000067956:Adenylyl Cyclase Inhibitors; D006063:Chorionic Gonadotropin; D003652:Decanoic Acids; D009842:Oligopeptides; D011974:Receptors, LH; D019308:Palmitic Acid; C031071:decanoic acid; D000262:Adenylyl Cyclases