Studies on Peptides. CLVI. Synthesis of Second Human Calcitonin Gene-Related Peptide (β-hCGRP) by Application of a New Disulfide-Bonding Reaction with Thallium (III) Trifluoroacetate

• Published in: Chemical & pharmaceutical bulletin Vol. 35; no. 12; pp. 4769 - 4776
• Main Authors: FUJII, NOBUTAKA, WATANABE, TOSHIHIRO, OTAKA, AKIRA, BESSHO, KIYOSHI, YAMAMOTO, ITSUO, NODA, TOSHIHARU, YAJIMA, HARUAKI
• Format: Journal Article
• Language: English
• Published: Tokyo The Pharmaceutical Society of Japan 01.12.1987; Maruzen; Japan Science and Technology Agency
• Subjects: air-oxidized disulfide bonding reaction; ammonium iodide; Calcitonin Gene-Related Peptide; Chemical Phenomena; Chemistry; diphenyl sulfide; Disulfides; Exact sciences and technology; Fluoroacetates; hard-acid deprotection; Humans; Indicators and Reagents; inhibitory bone calcium resorption; lowering serum calcium; lowering serum phosphate ion; Met (O) reduction; Neuropeptides - chemical synthesis; new disulfide bonding reaction; Organic chemistry; Peptides; Preparations and properties; second human calcitonin gene-related peptide synthesis; soft base; Thallium; thallium trifluoroacetate oxidation; Trifluoroacetic Acid; trimethylsilyl trifluoromethanesulfonate deprotection; Organic disulfide; Liquid phase; Sulfur peptide; Peptide hormone
• ISSN: 0009-2363; 1347-5223
• DOI: 10.1248/cpb.35.4769

A 37-residue peptide corresponding to the entire amino acid sequence of second human calcitonin gene-related peptide (β-hCGRP) was synthesized by assembling seven peptide fragments, followed by two successive treatments; i.e., first with thallium (III) trifluoroacetate to establish the disulfide bond between two Cys (Ad) residues and then with 1 M trimethylsilyl trifluoromethane-sulfonate/trifluoroacetic acid in the presence of diphenyl sulfide and ammonium iodide to remove all protecting groups employed and at the same time to reduce Met (O) to Met. The result was compared with that obtained by the usual air-oxidation procedure. Synthetic β-hCGRP exhibited a weak inhibitory action against bone Ca-resorption stimulated by [1-34] -parathyroid hormone in vitro and lowered the Ca and Pi levels in rat serum.