Antibody purification by affinity chromatography based on small molecule affinity ligands identified by SPR-based screening of chemical microarrays.

Libraries of small molecules were searched for Fc-fragment selective binders to a recombinant human antibody ("MDJ8″, IgG(1)-subtype, κ-light chain) via SPR-based screening of chemical microarrays. Identified hit structures were immobilised on NHS-activated Sepharose for the determination of MDJ8 binding and selectivity versus typical proteineous impurities represented by the spend cell culture supernatant. Columns were packed and the most promising ligands further characterized in terms of binding constants, binding kinetics, as well as dynamic and equilibrium binding capacities.

Dialkynylpyrenes: strongly fluorescent, environment-sensitive DNA building blocks.

Two isomeric dialkynylpyrene phosphoramidites and their incorporation into oligonucleotides are described. The pyrene units closely resemble the well-known perylene bisimide dye PDI with regard to the ability to self-organize within a DNA duplex. In addition, dialkynylpyrenes exhibit significant monomer and remarkably strong excimer fluorescence.

Self-organization of polyaromatic compounds within DNA.

The structural organization of oligopyrene sections embedded within a DNA framework is described. Absorbance, fluorescence and circular dichroism spectroscopy provide insight into the molecular interactions of the pyrene units.

A highly practical RCM approach towards a molecular building kit of spirocyclic reverse turn mimics.

The development of privileged molecular scaffolds efficiently mimicking reverse turn motifs and thus increasing both binding and selectivity and enabling the elucidation of the bioactive conformation of a natural peptide has attracted remarkable interest. The frequent occurrence of proline in various turn patterns initiated the design of proline-based reverse turn mimetics. As a structural hybridization of a highly potent type VI beta-turn inducer 1 with saturated spirocyclic lactams 3 efficiently mimicking type II beta turns, we developed a versatile synthetic route towards unsaturated spirocyclic lactams of type 2, when Seebach's self-reproduction of chirality methodology was combined with a peptide coupling reaction and Grubbs' ring-closing metathesis.

Chirospecific synthesis of spirocyclic beta-lactams and their characterization as potent type II beta-turn inducing peptide mimetics.

[reaction: see text] Starting from natural proline, a practical chirospecific synthesis of spirocyclic beta-lactams of type 2 is described when a methylene moiety showing minimal steric demand is employed as a constraint element for adjusting the dihedral angle psi(i + 1). Employing the concept of self-reproduction of chirality, C-formylation of the oxazolidinone 5 afforded the key intermediate 7 taking advantage of an intermediate protection of the bridging element as a vinyl moiety. NMR- and IR-based conformational studies clearly indicated that spiro-beta-lactams of type 2 can serve as efficient beta-turn nucleators.

Evaluation of lactam-bridged neurotensin analogues adjusting psi(Pro10) close to the experimentally derived bioactive conformation of NT(8-13).

The neurotensin C-terminal hexapeptide, NT(8-13), which has been found to adopt a beta-strand-like conformation while bound to the NT1 receptor, was modified by the introduction of conformational constraints. Synthesis of the four stereoisomeric 4.4-spirolactams 1-4 and subsequent NT1 receptor binding studies showed that the restriction of psi(Pro10) to approximately 130 degrees leads to a more than 1000-fold increase of binding affinity for 1 (Ki = 12 nM) when compared to the more flexible analogue [NMeTyr11]NT(8-13).