Hydrogen-bond recognition of cyclic dipeptides in water

Abstract

An amide macrocycle with a highly preorganised cavity containing both polar and non-polar recognition sites forms stable complexes with cyclic dipeptides in water via amideamide hydrogen-bonds, NH-p hydrogen-bonds and hydrophobic contacts.

Binding Mechanisms in Supramolecular Complexes

“…Benzene, for example, associates with water in the gas phase with a stability of about 10 kJ mol À1 , [388] in agreement with ab initio calculations for OH-p and NH 3 -p complexes. [390] The interaction between the guest NH protons and the host phenyl ring in this case is also apparent from crystallography. [389] The formation of hydrogen bonds between CONH groups and aromatic groups in chloroform led to a cyclophane showing association constants with diamides that were increased by a factor of 10 4 relative to guest molecules lacking the acidic NH group.…”

A fluorine scan of non-peptidic inhibitors of neprilysin: Fluorophobic and fluorophilic regions in an enzyme active site

“…This water molecule however does not seem to be conserved, as it is absent in other crystal structures (PDB codes 1R1I, 1R1J, 1DMT), and the energetics of its displacement are difficult to be estimated. On the other hand, the terminal phenyl ring in (+)-2a/b benefits from S Met579 Á Á Áp interactions [41] and in particular from a favorable N-HÁ Á Áp interaction with the NH residue of the indole ring of Trp693 [42]. Overall, energetic gains and losses seem to balance out since the biphenyl derivatives (+)-2a/b are not more active than the benzyl derivatives (+)-1a/b (Table 1).…”

Bindungsmechanismen in supramolekularen Komplexen

“…[389] Ein Cyclophan zeigt mit einem Diamid durch Wasserstoffbrücken zwischen CONH und Aromaten in Chloroform Assoziationskonstanten, die durch die auch kristallographisch sichtbare Wechselwirkung zwischen den Gast-NH-Protonen und den Wirt-Phenylringen um den Faktor 10 4 höher ist als bei Gastmolekülen ohne die aciden NH-Gruppen. [390] Dabei spielt allerdings auch die in Amiden erhöhte Basizität der Carbonylgruppe ein Rolle (Schema S14).…”