Holder Jerry Ryan, Haskell-Luevano Carrie
Department of Medicinal Chemistry, University of Florida, Gainesville, Florida 32610, USA.
Med Res Rev. 2004 May;24(3):325-56. doi: 10.1002/med.10064.
The challenge of peptide and peptidomimetic research is the development of methods and techniques to improve the biological properties of native peptides and to convert peptide ligands into non-peptide compounds. Improved biological properties of peptides includes enhancement of stability, potency, and receptor selectivity, for both in vivo and in vitro applications. The design of a ligand with specific activity and desired biological properties is a complex task, and, to accomplish this objective, knowledge about putative interactions between a ligand and the corresponding receptor will be valuable. This includes interactions for both the binding and signal transduction processes. Structure-activity relationship (SAR) studies involve systematic modification of a lead peptide and are designed to provide insight into potential interactions involved in the formation of the ligand-receptor complex. It is desirable to have knowledge about both favorable and unfavorable processes that may occur in putative ligand-receptor interactions that result in either receptor stimulation or inhibition. Herein, we discuss various SAR studies that have involved melanocortin peptides over three decades and the information these studies have provided to the melanocortin field.
肽和拟肽研究面临的挑战是开发方法和技术，以改善天然肽的生物学特性，并将肽配体转化为非肽化合物。肽生物学特性的改善包括增强稳定性、效力和受体选择性，适用于体内和体外应用。设计具有特定活性和所需生物学特性的配体是一项复杂的任务，为实现这一目标，了解配体与相应受体之间可能的相互作用将很有价值。这包括结合和信号转导过程中的相互作用。构效关系（SAR）研究涉及对先导肽进行系统修饰，旨在深入了解配体-受体复合物形成过程中潜在的相互作用。了解在可能导致受体刺激或抑制的假定配体-受体相互作用中可能发生的有利和不利过程是很有必要的。在此，我们讨论了三十多年来涉及黑皮质素肽的各种SAR研究，以及这些研究为黑皮质素领域提供的信息。
