First synthesis of a fully active spin‐labeled peptide hormone 1

• Published in: FEBS letters 1999-03, Vol.446 (1), p.45-48
• Main Authors: Barbosa, Simone R, Cilli, Eduardo M, Lamy-Freund, M.Teresa, Castrucci, Ana Maria L, Nakaie, Clovis R
• Format: Article
• Language: English
• Subjects: 2-BrZ, 2-bromobenzyloxycarbonyl; 2-ClZ, 2-chlorobenzyloxycarbonyl; Ac, acetyl; Boc, tert-butyloxycarbonyl; Bzl, benzyl; C18, octadecyl; DCM, dichloromethane; DIEA, N,N-diisopropylethylamine; DMF, N,N-dimethylformamide; DMS, dimethylsulphide; EDT, ethanedithiol; Electron spin resonance; Fmoc, 9-fluorenylmethyloxycarbonyl; For, formyl; HOBt, 1-hydroxybenzotriazole; HPLC, high performance liquid chromatography; MBHAR, methylbenzohydrylamine-resin; MeCN, acetonitrile; NMP, 1-methyl-2-pyrrolidinone; OcHex, cyclohexyl; Skin pigmentation; Spin-labeled peptide; TBTU, 2-(1H-benzotriazole-1-yl)-1,1,3,3-tetramethyluronium tetrafluoroborate; TFA, trifluoroacetic acid; Toac, 2,2,6,6-tetramethylpiperidine-1-oxyl-4-amino-4-carboxylic acid; Tos, p-toluenesulfonyl; α-Melanocyte stimulating hormone
• ISSN: 0014-5793; 1873-3468
• DOI: 10.1016/S0014-5793(99)00172-6

For the first time in the electron spin resonance (ESR) and peptide synthesis fields, a fully active spin‐labeled peptide hormone was reported. The ESR spectra of this α‐melanocyte stimulating hormone (α‐MSH) analogue (acetyl‐Toac0‐α‐MSH) where Toac is the paramagnetic amino acid probe 2,2,6,6‐tetramethylpiperidine‐1‐oxyl‐4‐amino‐4‐carboxylic acid, suggested a pH‐independent conformation and a more restricted movement comparatively to the free Toac. Owing to its equivalent biological potency in a skin pigmentation assay as compared to the native α‐MSH and its unique characteristic (paramagnetic, naturally fluorescent and fully active), this analogue is of great potential for investigation of relevant physiological roles reported for α‐MSH.