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F. HEITZ F. KADDARI A. HEITZ H. RANIRISEHENO R. LAZARO 《Chemical biology & drug design》1987,30(6):801-807
Peptides with sequences related to HC toxin (cyclo(l Ala-d Ala-l -Aoe-d Pro)) can adopt a conformation locked by three γ turns. A “structure — spectroscopy characteristics” relationship is proposed. These peptides can complex Mg++ cations and the binding is accompanied by a transconformation of the peptide backbone. The relevance with the biological activity of the toxin is discussed. 相似文献
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JACEK PINSKI TETSU YANO TAMAS JANAKY ATTILA NAGY ATTILA JUHASZ LAZARO BOKSER KATE GROOT ANDREW V. SCHALLY 《Chemical biology & drug design》1993,41(1):66-73
A series of new highly potent LH-RH antagonists (T-series) has been synthesized in our laboratory. Among these analogs, antagonists [Ac-d -Nal(2), d -Phe(4Cl)2. d -Pal(3)3, d -Lys(A2pr(Car)2)6, d -Ala10LH-RH (T-140); [Ac-d -Nal(2)1, d -Phe(4Cl)2, d -Pal(3)3, d -Lys(A2pr(Ac)2)6, d -Ala10]LH-RH (T-148); [Ac-d -Nal(2)1, d -Phe(4Cl)2, d -Pal(3)3, d -Lys(A2pr(For)2)6, d -Ala10)]LH-RH (T-151) and [Ac-d -Nal(2)1, d -Phe(4cl)2, d -Pal(3)3, d -Lys(A2bu(For)2)6, d -Ala10]LH-RH (T-159) were the most powerful. Antagonists T-140, T-148 and T-151 produced a complete blockade of ovulation in normal cycling rats at a dose of 1.5 μg/rat and antagonist T-159 at a dose of only 0.75 μg/rat. The inhibitory effects of compounds T-148, T-151 and T-159 on gonadotropin and sex steroid secretion were investigated in male and female rats. To determine their effect on LH levels in castrated male and ovariectomized female rats, T-148, T-151 and T-159 were injected subcutaneously in doses of 0.625 and 2.5 μg/rat. Blood samples were taken at different intervals for 48 h. All three compounds at either dose caused a significant (P< 0.01) decrease in LH levels for more than 6 h. Significant (P <0.01) inhibition of LH lasted for more than 24 h following a dose of 2.5 μg sc of all 3 antagonists in both male and female rats. Serum FSH levels were also suppressed significantly for more than 48 h in castrated male rats by all three antagonists at a dose of 5 μg/rat sc. Serum testosterone levels were measured in intact male rates injected with antagonists T-148, T-151 and T-159 in doses of 50 and 100 pg sc. Both doses produced a dramatic fall in testosterone (P<0.01) to castration levels 6 h after injection. The inhibition of serum testosterone lasted for more than 48 h, but only 100 μg of T-148 maintained testosterone in the castration range for more than 48 h. Antagonists T-148, T-151 and T-159 injected at a dose of 100 μg to intact female rats reduced serum estradiol levels significantly (P<0.01) for more than 48 h, as compared to control animals. In the cutaneous anaphylactoid test (CAT), T-148, T-151 and T-159 proved to have very low histamine releasing activities. These data demonstrate a high efficacy of these new LH-RH antagonists in suppressing the pituitary-gonadal axis in male and female rats. These LH-RH antagonists could possibly be used for treatment of sex-hormone sensitive cancers and other disorders and conditions, in which a reduction in circulating sex steroids would be beneficial. 相似文献
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SANDOR BAJUSZ VALER J. CSERNUS TAMAS JANAKY LAZARO BOKSER MATYAS FEKETE ANDREW V. SCHALLY 《Chemical biology & drug design》1988,32(6):425-435
Modifications of the previously described LHRH antagonists, [Ac-d -Nal(2)1, d -Phe(4Cl)2, d -Trp3, d -Cit6, d -Ala10]LHRH and the corresponding d -Hci6 analogue, have been made to alter the hydrophobicity of the N-terminal acetyl-tripeptide portion. Substitution of d -Trp3 with the less hydrophobic d -Pal(3) had only marginal effects on the antagonistic activities and receptor binding potencies of the d -Cit/d -Hci6 analogues, but it appeared to further improve the toxicity lowering effect of d -Cit/d -Hci6 substitution. Antagonists containing d -Pal(3)3 and d -Cit/d -Hci6 residues, i.e. [Ac-d -Nal(2)1, d -Phe(4Cl)2, d -Pal(3)3d -Cit6, d -Ala10]LHRH (SB-75) and [Ac-d -Nal(2)1, d -Phe(4Cl)2, d -Pal(3)3, d -Hci6, d -Ala10]LHRH (SB-88), were completely free of the toxic effects, such as cyanosis and respiratory depression leading to death, which have been observed in rats with the d -Trp3, d -Arg6 antagonist and related antagonists. Replacement of the N-acetyl group with the hydrophilic carbamoyl group caused a slight decrease in antagonistic activities, particularly in vitro. Introduction of urethane type acyl group such as methoxycarbonyl (Moc) or t-butoxycarbonyl (Boc) led to analogues that showed LHRH-potentiating effect. The increase in potency induced by these analogues, e.g. [Moc-d -Nal(2)1, d -Phe(4Cl)2, d -Trp3, d -Cit6, d -Ala10]LHRH and [Boc-d -Phe1, d -Phe(4Cl)2, d -Pal(3)3, d -Cit6, d -Ala10]LHRH, was 170-260% and persisted for more than 2 h when studied in a superfused rat pituitary system. 相似文献
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Restoration and Maintenance of Spermatogenesis by HCG Therapy in Patients with Hypothalamo-Hypophyseal Damage 总被引:1,自引:0,他引:1
O. LEVALLE L. BOKSER N. PACENZA G. ASZENMIL L. FISZLEJDER A. CHERVIN and A. GUITELMAN 《Andrologia》1984,16(4):303-309
Both gonadotropins are necessary to induce spermatogenesis in man and to recover hypophysectomized males. The patients who suffer from tumoral or traumatic hypothalamo-hypophyseal lesion use to have low endogenous gonadotropins (opposite to hypophysectomized patients), which can produce a minor involution of spermatogenesis. Three patients with postpubertal hypogonadotropic hypogonadism and oligozoospermia were studied. Two of them were operated on for chromophobous adenoma of pituitary, and the other patient had traumatic hypothalamo-hypophyseal lesion. The three patients were treated with 5000 IU HCG/week, associated with testosterone enanthate, in two cases and with bromocryptine in the remaining one. All the patients had normalized spermiogram, but when HCG was interrupted, the sperm count regressed to pretreatment levels in spite of the maintenance of treatment with testosterone or bromocryptine. Minimal amounts of FSH together the testosterone supplied by Leydig cell under the HCG stimulus, are able to recover and maintain the spermatogenesis in these patients. 相似文献
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VALRIE FULCRAND ROBERT JACQUIER REN LAZARO PHILIPPE VIALLEFONT 《Chemical biology & drug design》1991,38(3):273-277
Copolymers of acrylated derivatives of α-chymotrypsin and polyethylene glycol (PEG) have been prepared and used as biocatalysts for the synthesis of model peptides in organic solvent containing a low quantity of water. Other peptide couplings have been tried to point out the chemico- and stereoselectivity and examples of segment couplings are given. 相似文献
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