Michael B. Doughty

Neuropeptide Y (NPY) functional group mimetics: design, synthesis, and characterization as NPY receptor antagonists

Abstract N,N′-bis-[2-N-(O-2,6-dichlorobenzyl-L-tyrosyl)aminoethylguanyl]cystamine 3 and N,N′-bis-[2-N-(O-2,6-dichlorobenzyl-L-tyrosyl)aminoethyl]-1,6-hexanediguanidine 4 have been designed as neuropeptide Y (NPY) functional group mimetics. Both 3 and 4 displace N-[propionyl- 3 H]-NPY from rat brain binding sites, and are NPY receptor antagonists in rat femoral artery ring segments.

Synthesis of 2-Azido-1,N6-Etheno and 2-Azido Analogs of Deoxyadenosine as Nucleotide Photoaffinity Probes

Abstract We prepared 2-azido-1, N6-etheno-2′-deoxyadenosine 5′-monophosphate (7b) by activation of the 2-thio analog 4b by two methods. In the preferred method, 4b was treated with 2,4-dinitrofluorobenzene in 50% aqueous acetonitrile, and the resultant thioether was cleaved with hydrazoic acid, yielding the 2-azido-1, N6-etheno analog 7b in 70% isolated yield. N-bromoacetamide oxidized the etheno group of 7b, giving the 2-azido analog of dAMP 9b in 78% yield.

Neuropeptide Y acylation chemistry in aqueous solution: Significance to synthesis of a peptide-based photoaffinity label

Treatment of neuropeptide Y (NPY,1) for 20 hr with a 20 equivalent excess of N-propionyl succinimide (2) in 10 mM phosphate buffer,pH 6.0, yields NPY and Nα-propionyl-NPY (3) as major products, and atpH 7.5 the major product is Nα, Nε-dipropionyl-NPY. However, acylation of NPY with one equivalent of N-(5-azido-2-nitrobenzolyloxy)-succinimide (5) is more rapid, yielding Nα-(5-azido-2-nitrobenzoyl)-NPY (6) in 70% conversion yield after only 5 min. Thus, in spite of its increased reactivity, the N-hydroxysuccinimide active ester shows enhancedα- vs.ε-NH2 selectivity relative to2. The activities of3, 4, and6 as reversible, competitive ligands at rat brain NPY binding sites and of6 as an irreversible photoaffinity label are reported.