qualitative-identification-carboxylic-acids-boronic-acids-amines

Qualitative Identification of Carboxylic Acids, Boronic Acids, and Amines Using Cruciform Fluorophores

Molecular cruciforms are X-shaped systems in which two conjugation axes intersect at a central core. If one axis of these molecules is substituted with ...

Ruprecht-Karls-Universität Heidelberg

Miniproteins are scaffolds for the development of alternative non-immunoglobin binding agents for medical applications. This peptide format features high tolerance to sequence mutagenesis, excellent proteolytic stability, and fast blood pool clearance. Herein we present the total chemical synthesis of the disulfide-constrained scaffold Min-23 and its functionalization for inâ€…vitro and inâ€…vivo application. Optimized solid-phase peptide chemistry and oxidative folding strategies were developed to engineer this miniprotein with native-like disulfide configuration. High levels of serum stability and proteolytic resistance, as well as a beneficial pharmacokinetic profile for diagnostic imaging, were determined by using radiolabeling techniques such as positron emission tomography. The reported achievements highlight Min-23 as a promising scaffold for the development of novel recognition molecules for medical application.

Engineering and functionalization of the disulfide-constrained miniprotein min-23 as a scaffold for diagnostic application.

We developed a series of new conjugated cruciform fluorophores (XF) featuring imine groups. The condensation of an XF containing aldehyde functionalities and selected primary amines leads to several XF-imine derivatives. Upon addition of Cu(2+) or Zn(2+) ions to solutions of the imine XFs in different solvents, a red-shifted emission is detected, resulting in an altered emission color. The imine acts as a simple modular metallo-reactive fluorophore.

Article	Year
Engineering and functionalization of the disulfide-constrained miniprotein min-23 as a scaffold for diagnostic application. ChemMedChem\| PubMed ID: 22213706	2012
Imine formation as a simple reaction to construct copper-reactive cruciform fluorophores. The Journal of organic chemistry\| PubMed ID: 23194075	2013

Thimon Schwaebel

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