Synthesis of a tritiated human growth hormone releasing peptide.
Tritium-labeled growth hormone releasing peptide His-D-Trp-Ala-Trp-D-Phe-Lys-NH2 was synthesized by tritium-halogen exchange on the precursor His-5,7-Br2-D-Trp-Ala-Trp-D-Phe-Lys-NH2. The radiolabeled peptide had a specific activity of 29 Ci/mmol and a radiochemical purity of 95%. The tritium label was shown by 3H NMR to be located mostly at the expected 5,7-positions of the indole nucleus in the D-Trp residue. The dibromopeptide was prepared by solid-phase peptide synthesis, employing racemic 5,7-Br2-Trp as a building block and separation of the resulting epimeric mixture by HPLC. 5,7-Br2-Trp was prepared by a five-step sequence beginning with 2,4-dibromoaniline. The use of anisole as an additive in the HF resin/peptide cleavage was rejected because anisole was found to undergo electrophilic substitution of the dibromoindole nucleus; a modified HF deprotection/cleavage procedure was developed and used instead.
Shu
A Y
AY
Department of Synthetic Chemistry, SmithKline Beecham Pharmaceuticals, King of Prussia, Pennsylvania.
Heys
J R
JR
D000595:Amino Acid Sequence; D006728:Hormones / Q000138:chemical synthesis*; D006801:Humans; D006858:Hydrofluoric Acid; D009682:Magnetic Resonance Spectroscopy; D008969:Molecular Sequence Data; D015394:Molecular Structure; D009842:Oligopeptides / Q000138:chemical synthesis*; D014316:Tritium
D006728:Hormones; D009842:Oligopeptides; D014316:Tritium; C041048:growth hormone releasing hexapeptide; D006858:Hydrofluoric Acid