Abstract
G-protein-coupled receptors associate into dimers/oligomers whose function is not well understood. One approach to investigate this issue is to challenge oligomerization by peptides replicating transmembrane domains and to study their effect on receptor functionality. The disruptor peptides are typically delivered by means of cell-penetrating vectors such as the human immunodeficiency virus (HIV) transcription trans-activation protein Tat. In this paper we report a cyclic, Tat-like peptide that significantly improves its linear analogue in targeting interreceptor sequences in the transmembrane space. The same cyclic Tat-like vector fused to a transmembrane region not involved in receptor oligomerization was totally ineffective. Besides higher efficacy, the cyclic version has enhanced proteolytic stability, as shown by trypsin digestion experiments.