Flexible but with a defined turn-influence of the template on the binding properties of two-armed receptors.
Combinatorial binding studies revealed that the di(trans-4-aminoproline)diketopiperazine is an ideal template for two-armed receptors with highly selective binding properties towards peptides. It is not only superior to structurally very different diamines but also to the diastereomeric di(cis-4-aminoproline)diketopiperazine. These empiric results are rationalized by the analysis of the conformation of the diastereomeric diketopiperazines in the solid state, by X-ray crystal structure analysis, as well as by NMR studies in solution: to observe highly selective binding, the template needs to be not only conformationally rigid but it must have a specific turn geometry. The combination of combinatorial binding studies, X-ray crystal structure analysis, and NMR spectroscopy gave insight into why the trans,trans-diketopiperazine is a superior template compared to other diamines. Additionally, the results provide a guide for the rational design of two-armed receptors with good binding properties towards peptidic guests.
Wennemers
Helma
H
Department of Chemistry, University of Basel St. Johanns Ring 19, 4056 Basel, Switzerland. Helma.Wennemers@unibas.ch
Nold
Matthias C
MC
Conza
Matteo M
MM
Kulicke
Klaus J
KJ
Neuburger
Markus
M
D001665:Binding Sites; D020650:Combinatorial Chemistry Techniques; D018360:Crystallography, X-Ray; D009682:Magnetic Resonance Spectroscopy; D008958:Models, Molecular; D015394:Molecular Structure; D010455:Peptides / Q000737:chemistry* / Q000378:metabolism*; D010879:Piperazines / Q000737:chemistry* / Q000378:metabolism*; D018583:Pliability; D011485:Protein Binding; D013379:Substrate Specificity
D010455:Peptides; D010879:Piperazines