Sequence-selective Recognition of Peptides by Aminopyrazoles

To avoid self-association the overall shape of larger structures has been chosen to be slightly curved, or ionic groups have been incorporated for recognition of the N-or C-terminus. 

No self-association occurs between the receptor molecules of 4 in a concentration range between 10-2 m and 10-3 m, as was proven with a dilution experiment. Hence, all complexation studies were performed with alanine-containing dipeptides in this concentration range. As usual, the peptide s top face NH proton shows a downfield shift on complexation with the aminopyrazole. In almost every exam- 

With our nitroarene tip in host 5, we tried to establish additional n-n interactions with electron-rich residues in aromatic amino acids. To this end, we titrated Ac-Phe-Ala-OMe first with reference compound 3 and then with host 5 and obtained l l-association constants of 40 m-1 and 350 m-1, respectively. Again, a ninefold increase from the steric repulsion by the reference compound and the re-stacking attraction by host 5 was found. Substantial upfield shifts in the aromatic regions of host and guest 1H NMR spectra confirmed the additional stabilizing interaction. 

Karplus analyses of the NH-a-CH coupling constants which correlate with the characteristic torsion angle d, offer valuable information about the conformation of the peptide [17]. We compared the iJ values of the free peptides with those in the complex with their optimized binders. Usually signals became much sharper and the coupling constants markedly increased, approaching the calculated values (MacroModel). 

We are currently designing special recognition tips in our new hosts for nonpolar and acidic amino acids in peptides. We are also covalently connecting two or more of the modules to achieve predictable sequence-selective recognition of larger peptides (for another approach to peptide receptors see Chapters 2.3 and 3.1). This 

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