Recent advances in the investigation of the bioactive conformation of peptides active at the micro-opioid receptor. conformational analysis of endomorphins.
Despite of the recent advances in the structural investigation of complex molecules, the comprehension of the 3D features responsible for the interaction between opioid peptides and micro-opioid receptors still remains an elusive task. This has to be attributed to the intrinsic nature of opioid peptides, which can assume a number of different conformations of similar energy, and to the flexibility of the receptorial cavity, which can modify its inner shape to host different ligands. Due to this inherent mobility of the ligand-receptor system, massive efforts devoted to the definition of a rigid bioactive conformation to be used as a template for the design of new pharmacologically active compounds might be overstressed. The future goal might be the design of peptide or nonpeptide ligands capable of maximizing specific hydrophobic interactions. This review covers the recent opinions emerged on the nature of the ligand-receptor interaction, and the development of suitable models for the determination of the bioactive conformation of peptide ligands active towards micro-opioid receptors.
Gentilucci
Luca
L
Dipartimento di Chimica "G. Ciamician", via Selmi 2, Università degli Studi di Bologna, 40126-Bologna, Italy. gentil@ciam.unibo.it
Tolomelli
Alessandra
A
D001665:Binding Sites; D004723:Endorphins / Q000737:chemistry / Q000378:metabolism; D004745:Enkephalins / Q000737:chemistry / Q000378:metabolism; D057927:Hydrophobic and Hydrophilic Interactions; D008024:Ligands; D008958:Models, Molecular; D009842:Oligopeptides / Q000737:chemistry; D018847:Opioid Peptides / Q000737:chemistry / Q000494:pharmacology*; D011487:Protein Conformation; D017450:Receptors, Opioid, mu / Q000819:agonists* / Q000037:antagonists & inhibitors; D013329:Structure-Activity Relationship
D004723:Endorphins; D004745:Enkephalins; D008024:Ligands; D009842:Oligopeptides; D018847:Opioid Peptides; D017450:Receptors, Opioid, mu; C105293:endomorphin 1; C105294:endomorphin 2