Current Medicinal Chemistry - Volume 7, Issue 9, 2000

Current strategies in pharmaceutical research comprise two methodologically different but complementary approaches for lead finding purposes, namely the random screening of compound libraries and the structure-based effort, commonly termed rational drug design. The structure-based approach is aimed to exploit 3D structure data of the molecular compo-nents involved in the molecular recognition event that underlies Read More

During the past 10 years or so, associated with the introduction of molecular biology techniques to G protein coupled receptor (GPCR) research, outstanding progress has been made in understanding the mechanisms of action of these key proteins and their physiological functions. in vivo manipulation of levels of GPCRs using transgenic and gene knock out approaches have been particularly successful in assessing the role Read More

G-protein-coupled receptors constitute a superfamily of integral membrane proteins encompassing hundreds of receptors for all types of chemical messengers, as well as, for example, the key molecules of our light and smell sensory systems, bioactive amines, peptide hormones, neurotrans-mitters and even proteins. Because of their complicated organisation with the characteristic seven transmembrane segments (7 TM) it h Read More

G protein-coupled receptors (GPCRs) represent a major class of drug targets. Recent investigation of GPCR signaling has revealed interesting novel features of their signal transduction pathways which may be of great relevance to drug application and the development of novel drugs. Firstly, a single class of GPCRs such as the bradykinin type 2 receptor (B2R) may couple to different classes of G proteins in a cell-specific and tim Read More

The design of peptidomimetic ligands with agonist biological activities in vitro and in vivo has been challenging. Lofty goals have been set for this research including high potency, high receptor type selectivity, high stability in vitro and in vivo, and high efficacy in vitro and in vivo for agonists. A systematic stepwise strategy has been developed to accomplish these goals. These include determining the primary amino acid side ch Read More

Receptor targeting with radiolabeled peptides has become very important in nuclear oncology in the past few years. The most frequently used peptides in the clinic are analogs of somatostatin (SRIF), e.g. OctreoScan, which contain chelators for the radioisotopes 111 In, 86Y, 90 Y, 67Ga, 68Ga and 64Cu or for 99m Tc and 188Re. and were labelled with the halogens 123I and 18F. Radiolabeled analogs of a-melanocyte-stim Read More