Flexible but with a defined turn-influence of the template on the binding properties of two-armed receptors

Chemistry : a European Journal
Helma WennemersMarkus Neuburger

Abstract

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.

Citations

Aug 10, 2006·Chemical Communications : Chem Comm·Miwa KuboHideaki Hioki
Jun 9, 2004·Current Opinion in Chemical Biology·Natarajan Srinivasan, Jeremy D Kilburn
Jul 13, 2016·Biopolymers·Claudio E GrünenfelderHelma Wennemers

Related Concepts

In Vivo NMR Spectroscopy
Polypeptides
Piperazines
Plasma Protein Binding Capacity
Substrate Specificity
Crystallography, X-Ray
Combinatorial Chemistry Techniques

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