Synthesis and screening of libraries of synthetic tripodal receptor molecules with three different amino acid or peptide arms: identification of iron binders

A novel selectively deprotectable triazacyclophane scaffold was used for the design and split−mix synthesis of two libraries of solid-phase bound tripodal synthetic receptors possessing three different amino acid or peptidic arms. In the synthesis of the first library, the two outer arms consisted of amino acid Ala, Arg, Asp, Gln, Gly, Lys, Phe, Ser, Tyr, or Val and the middle arm consisted of amino acid Asn, Glu, His, Leu, or Pro. The second library contained amino acid and/or (di)peptide arms. The arms were different in all library members. The first outer arm consisted of amino acid(s) Ala, Arg, Gln, Phe, or Ser, the second outer arm consisted of amino acid(s) Asp, Gly, Lys, Tyr, or Val, and the middle arm consisted of amino acid(s) Asn, Glu, His, Leu, or Pro, leading to a 27 000 member library of synthetic tripodal receptor molecules. In on-bead screening experiments, a remarkable selectivity of some library members for Fe3+ was observed and decoding of their structures by Edman degradation revealed consensus sequences with structural resemblance to non-heme iron proteins

Bioinspired Chemistry Based on Minimalistic Pseudopeptides

For years researchers have tried to understand the molecular behavior of complex biomolecules through the development of small molecules that can partially mimic their function. Now researchers are implementing the reverse approach: using the structural and mechanistic knowledge obtained from those complex systems to design small molecules with defined properties and for specific applications. One successful strategy for constructing bioinspired, minimalistic molecules is to combine natural building blocks that provide functional elements with abiotic fragments that serve as structural scaffolds. Therefore pseudopeptidic compounds, most of them based on C2 symmetric structures, represent a unique opportunity to explore and evaluate this approach. Some of these molecules are as simple as two amino acids connected by a diamino spacer. The results in this Account show how bioinspired minimalistic pseudopeptides can form ordered structures, participate in the recognition and transcription of information events in molecular devices, and catalyze reactions. This strategy allows researchers to design and prepare a variety of open-chain and macrocyclic compounds leading to systems that can self-aggregate to form hierarchically ordered micro- and nanostructures. In addition, small changes in the molecule or external stimuli can regulate the self-aggregation pattern. In the same way, researchers can also tune the molecular movements of simple pseudopeptides through environmental factors, providing a means to control new molecular devices. In addition, some of the prepared model compounds have shown interesting properties in molecular recognition and even as sensors for several targets of interest. Finally we have observed remarkable catalytic activities from these types of molecules, although those results are still far from the efficiency shown by natural peptides. This family of pseudopeptidic compounds offers the opportunity for the more elaborate design of relatively simple abiotic but bioinspired systems that display specific properties. In addition, the results can provide additional information that will increase the molecular understanding of the basic principles that underlie the extraordinary behavior of natural systems