Active reduced-size hexapeptide analogs of luteinizing hormone-releasing hormone

Citations Over Time

Abstract

A series of reduced-size hexapeptide analogues of LH-RH were synthesized that contain the residues corresponding to amino acid positions 4-9 and are linked to various carboxylic acids in place of residue 3. These compounds were tested in vitro in the rat pituitary receptor binding and LH release assays. A wide range of binding affinities was obtained up to and exceeding that of LH-RH. Both agonists and antagonists were obtained. From the SAR studies, it appears that a very precise size, length, and shape of the substituent at position 3 is required to achieve agonist activity, whereas the structural requirements for antagonist activity appear to be much less stringent. Depending on the nature of the substituent at positions 6 and 4, the biological response switches from antagonist to agonist or vice versa. The results suggest that conformational changes at position 6 or 4 feed back to the substituent at position 3, which induces the change from agonist to antagonist. The most potent compounds in the series were tested in vivo and found to be active.

Related Papers

• → Growth hormone binding protein in the rat: effects of gonadal steroids.(1993)59 cited
• → Exogenous Glucocorticoids and a High-Fat Diet Cause Severe Hyperglycemia and Hyperinsulinemia and Limit Islet Glucose Responsiveness in Young Male Sprague-Dawley Rats(2013)47 cited
• → The Paraventricular Nucleus of the Hypothalamus Has a Major Role in Thyroid Hormone Feedback Regulation of Thyrotropin Synthesis and Secretion(1990)53 cited
• → The Effect of Fasting on Tissue Cyclic cAMP and Plasma Glucagon in the Obese Hyperglycemic Mouse(1975)39 cited
• → Modulation of Adipoinsular Axis in Prediabetic Zucker Diabetic Fatty Rats by Diazoxide(2004)39 cited