Utilizing Peptide Structures As Keys For Unlocking Challenging Targets

Title: Utilizing Peptide Structures As Keys For Unlocking Challenging Targets

Volume: 6 Issue: 9

Author(s): David Fry and Hongmao Sun

Affiliation:

Keywords: Structure of peptide, NMR, pharmacophore, small molecule drug design

Abstract: Three-dimensional structures of protein targets have proven to be extremely valuable for modern drug design and discovery. For cases where the structure of the protein is unattainable, such as G-protein coupled receptors (GPCRs), structural information on active ligands is still useful and helpful for deciphering the geometrical and chemical features of the active site. Peptides, constructed from easy-to-form amide backbones and featuring variable side-chains, have an inherent advantage in generating rapid quantitative structure-activity relationships (QSAR). Given the fact that peptides are natural ligands for many protein targets, structural investigation of a series of related peptides, typically carried out via nuclear magnetic resonance (NMR), can result in an accurate pharmacophore model. Such a model can be used for virtual screening, and to assist design of second-generation peptidomimetics with improved properties and design of non-peptidic leads. In this article, we will review examples in which a structural approach utilizing peptide ligands was employed to obtain a better understanding of the target active site. We will focus on cases where such information supplied guidance toward the discovery of small molecule ligands.

Cite this article as:

Fry David and Sun Hongmao, Utilizing Peptide Structures As Keys For Unlocking Challenging Targets, Mini-Reviews in Medicinal Chemistry 2006; 6 (9) . https://dx.doi.org/10.2174/138955706778195171