High-affinity reporter peptides

In comparison to a reporter peptide, the affinity of human TAP for a totally degenerate nonapeptide library was found to be 17-fold lower [20]. Single amino acid substitutions in the high-affinity reporter peptides resulted in only two- to three-fold differences in transport rates, but in up to 80-fold differences as revealed by the use of synthetic peptide libraries. 

Quinolinyl compounds were first reported by Chan et al. as potent orexin receptor antagonists with excellent selectivity for OX1, good brain permeability and in vivo activity following i.p. dosing [62,63]. In fact, compounds SB-334867 (21), SB-408124 (22) and SB-410220 (23) displayed high affinity for the OX1 receptor in both whole cell (Ki — 99, 57 and 19nM, respectively) and membrane formats (X = 38, 27 and 4.5 nM, respectively). Meanwhile, native orexin peptides A and B display affinities for the OX1 receptor with K values of 318 and 1516 nM, respectively. In addition, calcium mobilization studies showed that all three are functional antagonists of the OX1 receptor, with potencies in line with their affinities, and with 50-fold... 

Cyclic peptides have been reported to bind to multiple, unrelated classes of receptor with high affinity. Owing to the robustness of amide bond chemistry, the ability to explore extensive chemical diversity by incorporation of unnatural and natural amino acids, and the ability to explore conformational diversity, through the incorporation of various constraints, arrays of cyclic peptides can be tailored to broadly sample chemical diversity. We describe the combination of a safety catch linker with a directed-sorted procedure for the synthesis of large arrays of diverse cyclic peptides for high-throughput screening. 

In this report, we summarize the results of a study in which the energetic barriers of several protein/complex decompositions were analyzed utilizing transition-state theory. In essence, fluorescein 5-isothiocyanate was covalently linked to a variety of synthetic peptides and allowed to bind with the well defined high affinity 4-4-20 mAb. Differences in the rates of decomposition were measured at 275 K and 291 K and the height of energetic barriers calculated using classical transition-state analysis (16). 

---