[Conformational analysis of biologically active thyroliberin analogs by two-dimensional NMR spectroscopy].

Preferable conformations of thyrotropin-releasing hormone (TRH, Glp-His-Pro-NH2) and its analogues Glp-Glu(R)-Pro-NH2 (R = NHCH(CH3)CH2Ar), Glp-Gln-Abu-NH2, Dho-Gln-Abu-NH2 in DMSO solution are determined using two-dimensional 1H NMR spectroscopy (delta-J-correlated, COSY and NOESY). Torsion angles psi i and chi i for every amino acid were calculated on the basis of the spin-spin coupling constants 3JNH-C alpha H and 3JC alpha H-C beta H values. The NOESY data were used for selecting the peptide conformations realized in solution.

[Protective action of thyroliberin and its synthetic analog (PR-546) in craniocerebral trauma].

The effect of TRH and its synthetic analogue (PR-546) devoid of hormonal activity was studied in acute experiments on rats on the model of neurogenic lung edema caused by skull injury. It was proved that the preliminary (for 30 min before the injury) i/p introduction of TRH (in doses 0.5-1 mg/kg) and PR-546 (in doses 4-8 mg/kg) prevented the development of acute edema and the changes of blood gas compositions as well as disorders in breathing after skull injury.

[Cyclic analogs of ACTH fragments in self-stimulation and grooming behavior in rabbits].

In present study new cyclic fragments of ACTH EHFRWGKPVG--NH2 and KHFRWG--NH2 were investigated in organization of self-stimulation and grooming behaviour in rabbits. Intracerebroventricular injections of EHFRWGPVG--NH2 in doses of 0.1-2.

[Effects of femto- and picomolar concentrations of thyroliberin and tuftsin on the contractile activity of lymphatic vessels of the rat mesentery].

Thyrotropin-releasing-hormone (TRH) in concentration from I g/ml to 1.10(-10) micrograms/ml and tuftsin (T) (10 micrograms/ml to 1.10(-6) micrograms/ml) biomicroscopy were used in rats to show the ability to activate the contraction of lymphatic microvascular walls.

[Recovery of impaired respiratory activity in cats by thyroliberin analog (PR-546) devoid of hormonal properties].

Synthetic analogue thyroliberin (PR-546) devoid of hormonal activity, recovered respiration in conditions of hyperventilation, two-sided vagotomy and hypoxia, caused by the 40-70% bleeding. PR-546 (in doses 100-500 micrograms/kg) intravenously injected was shown to abolish diagram activity decreased effect after hyperventilation. Injection of PR-546 to vagotomized cats in 1.

[Thyroliberin and its analog lacking hormonal properties stimulate respiratory center activity in the frog Rana temporaria].

It has been shown that thyroliberin and its synthetic analogue PR-546 injected into the lymphatic sacs (4.10(-7)-4.10(-9) g/kg) or applied to the medulla oblongata in the bulbar frogs (4.

[Recovery from disorders of respiratory activity in cats using thyroliberin].

Controlled lung hyperventilation in cats inhibited the activity of the diaphragm muscle with a subsequent stop of respiration after the end of hyperventilation. Thyroliberin (20-30 mg/kg) intravenously was shown to abolish these effects 15-20 min after application. Preliminary introduction of thyroliberin prevented the changes in the respiration rate and depth caused by vagotomy.

[Synthesis of [cyclo(Glu gamma-----epsilon Lys(Gly)]ACTH-(5-14) undecapeptide. Biological and physico-chemical properties of analogs of ACTH-(5-10)- and ACTH-(5-14)-peptides].

Modified corticotropin fragment - [Lys11 (Gly)]ACTH-(5-14)- and its cyclic analogue - [cyclo (Glu gamma----epsilon Lys (Gly)] ACTH-(5-14)-undecapeptides have been synthesized by classical approach. The cyclic structure has been fixed by amide bond between gamma-COOH group of glutamic acid and alpha-NH2 group of glycine coupled to the epsilon-NH2 group of lysine. Fragment condensation has been achieved by azide or dicyclohexylcarbodiimide methods.

[Synthesis and biological properties of a cyclic analog of ACTH-(5-14)-decapeptide].

A cyclic analogue and the corresponding linear segment of the corticotropin molecule, namely ACTH-(5-14)- and [cyclo (Glu gamma-epsilon Lys)]ACTH-(5-14)-decapeptide, both including the specific and unspecific active centers of the ACTH molecule, have been synthesized and studied. The cyclic structure is fixed by amide bond between the glutamic acid and lysine side chains. Condensation of fragments has been realized by azide or DCC/HOBT methods.

[Synthesis and analysis of potent cyclic analogs of the ACTH active center].

Linear and cyclic analogues of the specific active center of the ACTH molecule have been synthesized, viz. [Lis5]ACTH-(5-10)-, [Lys5, cyclo (Gly10----epsilon Lys5)]-ACTH-(5-10)-hexapeptides, [Lys5 (Gly)]ACTH-(5-10)- and [Lys5, Gly11, cyclo (Gly11----epsilon Lys5)]-ACTH-(5-11)-heptapeptides. The cyclic structures are fixed by covalent bond between the COOH-group of the C-terminal glycine and epsilon-amino group of a lysine residue.

[Structural and functional organization of ACTH: synthesis and properties of analogs of ACTH-(11-24)-tetradeca- and ACTH-(1-24)-tetracosapeptides containing hexa-amino acids instead of a natural sequence of ACTH 19-24 amino acids].

To assess the role of amino acid sequence ACTH 19-24 in the corticotropin structure and steroidogenic activity, the analogues of ACTH-(11-24)-tetradeca- and ACTH-(1-24)-tetracosapeptides containing hexaglycine, hexaphenylalanine, hexaglutamic acid or hexalysine instead of the natural 19-24 sequence have been synthesized by conventional methods. All these compounds in water have the CD curves characteristic of random coil, CD spectra of analogue ACTH-(1-24)-tetracosapeptide and hexalysine-containing analogue ACTH-(11-24)-tetradecapeptide in trifluoroethanol indicate the presence of alpha-helices. The latter compound manifested higher steroidogenic activity than ACTH-(11-24)-tetradecapeptide.