Influence of linker structure on the anion binding affinity of biscyclopeptides

Chronic pain 5 years after randomized comparison of laparoscopic and Lichtenstein inguinal hernia repair (Br J Surg 2010; 97: 600–608)

“…The results of the ITC measurements (Table 1) show that with a log K a value between 4 and 6 the monolinked bis‐cyclopeptide 2 b possesses very high sulfate affinity in the solvent mixtures studied, albeit an approximately one order of magnitude lower affinity than the previously described analogue containing a 2,2′‐(1,3‐phenylene)diacetic acid linker, which binds sulfate in H 2 O/CH 3 OH (1:1, v/v) with a log K a of 5.97 10e. As for other bis‐cyclopeptides investigated previously, complex formation in H 2 O/CH 3 OH is exothermic and has a favorable entropic contribution 10b,e. Interestingly, increasing the water content of the solvent mixture from 35 to 65 % has almost no effect on the enthalpy of the complex formation.…”

“… This peptide has been shown to bind inorganic anions such as sulfate or halide ions in the form of 2:1 complexes in competitive aqueous solvent mixtures in which the anion is sandwiched between two cyclopeptide rings and is engaged in hydrogen‐bonding interactions with six NH groups that point into the cavity. Covalent linkage of two cyclopeptide rings through one linker has furnished bis‐cyclopeptides that bind to anions in a 1:1 ratio with considerably higher efficiency than the monotopic analogue 1 10b–e. A logical extension of this approach is the introduction of three linkers between the cyclopeptide rings, which should give rise to anion‐binding molecular containers.…”

Anion recognition by cyclic peptides

“…53 A series of receptors, 24-26 in which the linkers become progressively more rigid were synthesised. Although, large differences in the anion affinity and selectivity of 24-26 were not observed, the thermodynamics of anion complexation were shown to be profoundly different as measured by isothermal calorimetric analysis.…”

Scaffold Design Using Computational Chemistry

“…This program follows a similar approach to the CAVEAT-based design in that the user defines the choice of functionality to bind the guest and their position relative to the guest. HostDesigner screens a library of potential linker structures to identify those suitable for connecting the receptor functionality in the desired orientation [5,18,[36][37][38][39][40]. This program also evaluates other design characteristics that must be performed in a more manual fashion with CAVEAT.…”

“…5.15) [40]. The crystal structure of the complex of iodide with two equivalents of a cyclic hexapeptide was used as the complex fragment.…”