The Study of Novel Peptide-Based Endothelin Receptor Antagonists
会议名称：《8th Chinese International Peptide Symposium》
会议日期：2004年
学科分类：1002[医学-临床医学] 100201[医学-内科学(含：心血管病、血液病、呼吸系病、消化系病、内分泌与代谢病、肾病、风湿病、传染病)] 10[医学]
摘 要：Endothelins (ET-1, ET-2 and ET-3) are very powerful vasoconstrictors. Elevated ET levels have been noted in a variety of diseases including pulmonary hypertension, myocardial infarction, renal failure, heart failure and sub-arachnoid hemorrhage. The studies on ET receptor antagonists may lead to some new therapeutical agents for diseases induced by ETs. We designed and synthesized a variety of novel peptide-based compounds and determined their bioactivities. The N-terminal chemical groups showed crucial function in improving its selectivity and affinity to ET receptors. The introduction of unnatural aromatic amino acids into these tripeptides was useful in the SAR studies . The objective of our work was to get new structural ET receptor antagonists with high activity and selectivity of subtype of the receptors and study the SAR of the new compounds. From the SAR studies, we concluded that the linear peptide-based ET receptor antagonists synthesized in our laboratory with following features might show high ac-