Gerd Schnorrenberg

BIIE0246: A selective and high affinity neuropeptide Y Y2 receptor antagonist

The in vitro biological characterisation of the first potent and selective non-peptide neuropeptide Y Y(2) receptor antagonist, (S)-N(2)-[[1-[2-[4-[(R,S)-5,11-dihydro-6(6h)-oxodibenz[b, e]azepin-11-yl]-1-piperazinyl]-2-oxoethyl] cylopentyl] acetyl]-N-[2-[1,2-dihydro-3,5(4H)-dioxo-1,2-diphenyl-3H-1,2, 4-triazol-4-yl]ethyl]-argininamid (BIIE0246) is reported. BIIE0246 displaced [125I]neuropeptide Y with high affinity (IC(50)=3.3 nM) from the human neuropeptide Y Y(2) receptor and proved to be highly selective. BIIE0246 displayed antagonistic properties and thus represents the first selective non-peptide neuropeptide Y Y(2) receptor antagonist.

Highly potent and small neuropeptide Y agonist obtained by linking NPY 1–4 via spacer to α‐helical NPY 25–36

Analogues of neuropeptide Y (NPY) containing small N‐ and C‐terminal segments linked via flexible spacer arms were found to exhibit receptor binding affinity constants almost as high as NPY as well as post‐ and presynaptic NPY‐agonistic activities. One of the most active analogues contains N‐terminal NPY segment 1–4 linked via ε‐aminocaproic acid (Aca) to the C‐terminal partially α‐helical peptide amide segment 25–36. NPY 1–4‐Aca‐25–36 is the first highly potent NPY agonist, which is of considerably reduced size in comparison to the native hormone. The analogues are accessible by solid‐phase synthesis using Fmoc strategy.

Fully automatic simultaneous multiple peptide synthesis in micromolar scale - rapid synthesis of series of peptides for screening in biological assays.

Abstract A new method of simultaneous multiple peptide syntheses on polystyrene support in the wells of microtiterplates is illustrated by the syntheses of 31 overlapping segments of endothelin. All reagent and solvent handling is automatically performed by a freely programmable robotic sample processor.