Peptoid mimics of agouti related protein

Bioorganic and Medicinal Chemistry Letters

Volumn 13, Issue 8, 2003, Pages 1409-1413

  Thompson, Darren A ^a   Chai, Biao Xin ^b   Rood, Hilary L E ^a   Siani, Michael A ^c   Douglas, Nicholai R ^a   Gantz, Ira ^b   Millhauser, Glenn L ^a  

^a UNIVERSITY OF CALIFORNIA   (United States)

^b UNIVERSITY OF MICHIGAN HEALTH SYSTEM   (United States)

^c Dept Bioinfo Affymetrix Berkeley ^*  (United States)

Author keywords

[No Author keywords available]

Indexed keywords

AGOUTI RELATED PROTEIN; ALPHA INTERMEDIN; CYCLIC AMP; GLYCINE DERIVATIVE; MELANOCORTIN 3 RECEPTOR; MELANOCORTIN 4 RECEPTOR; PEPTOID; RECEPTOR BLOCKING AGENT; UNCLASSIFIED DRUG;

ARTICLE; ATOM; CHEMICAL STRUCTURE; CHIRALITY; ISOTOPE LABELING; MOLECULAR MIMICRY; PROTEIN FUNCTION; SYNTHESIS;

AGOUTI;

EID: 0037451866     PISSN: 0960894X     EISSN: None     Source Type: Journal    
DOI: 10.1016/S0960-894X(03)00164-1     Document Type: Article

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23. Compound 1 synthesis 0.5 g Fmoc-Rink amide MBHA resin Novabiochem (San Diego, CA) was deprotected with 2×5 min 20% piperidine/DMF. The free amine was acylated with 2 mmol Fmoc-Aib-OH and DIC in DMF for 30 min, deprotected as before, the resulting amine was alkylated with a 1:1:3 Benzylbromide:DIEA:DMF solution for 1 h. Acylation of secondary amines was accomplished by DIC and Bromoacetic acid for 1.5 h. A 20% solution of Phenethylamine in DMSO was added and left overnight (typical yield <50%). The secondary amine acylated with bromoacetic acid/DIC for 30 min. Diaminopropane was added as a 2 M solution in DMSO for 1 h, followed by guanidinylation by 3,5-dimethylpyrazole carboxamidine nitrate (4 mmol 20% DIEA/DMF 50°C 1.5 h) Aldrich (Milwaukee, WI). The reaction vessel was DMF washed after every synthetic step. Reactions were at 35°C unless otherwise noted. MH+ calculated: 510.7 (ave. isotopes) found: 511.3. Typical peptoid synthesis 0.3 g Fmoc-Rink amide MBHA resin was deprotected with 2×5 min 20% piperidine/DMF. Step I: the amine was acylated with excess Bromoacetic acid/DIC for 30 min. Step II: 2 M solutions of primary amines in DMSO were added for 1-2 h. Steps I and II repeated two additional times, followed by guanidinylation of 3-aminopropyl side chains as before. The reaction vessel was DMF washed after every synthetic step.
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