Fast Fmoc synthesis of hAmylin1-37 with pseudoproline assisted on-resin disulfide formation.
Human amylin (1-37) and the (1-13) fragment were synthesized with and without pseudoproline dipeptides. Thallium (III) trifluoroacetate, a mild oxidant, was used to cyclize the peptides by forming a disulfide bridge from C(2) to C(7). On the basis of our model studies, incorporation of a pseudoproline dipeptide decreases the amount of time necessary for the crude linear amylin (1-13) to cyclize on the resin. Without pseudoproline dipeptides, the 1-37 crude linear amylin was not pure enough to undergo the cyclization reaction. Following the cyclization studies, the synthesis time of the linear human amylin (1-37) was systematically reduced from 58 h to 8.5 h by shortening the reaction times. Cyclization and cleavage times were also reduced to 1.5 h.
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Karen
K
Department of Chemistry, Protein Technologies Inc., Tucson, Arizona, 4675 South Coach Drive, Tucson, Arizona 85714, USA.
Hood
Christina A
CA
Patel
Hirendra
H
Fuentes
German
G
Menakuru
Mahendra
M
Park
Jae H
JH
D000596:Amino Acids / Q000737:chemistry*; D000682:Amyloid / Q000138:chemical synthesis* / Q000737:chemistry; D002851:Chromatography, High Pressure Liquid / Q000379:methods; D003500:Cyclization; D004220:Disulfides / Q000138:chemical synthesis* / Q000737:chemistry; D005449:Fluorenes / Q000737:chemistry*; D005463:Fluoroacetates; D006801:Humans; D058228:Islet Amyloid Polypeptide; D008968:Molecular Conformation; D009842:Oligopeptides / Q000737:chemistry; D011392:Proline / Q000031:analogs & derivatives* / Q000737:chemistry; D013237:Stereoisomerism; D013793:Thallium; D013844:Thiazoles / Q000737:chemistry*; D013997:Time Factors; D014269:Trifluoroacetic Acid / Q000737:chemistry
D000596:Amino Acids; D000682:Amyloid; D004220:Disulfides; D005449:Fluorenes; D005463:Fluoroacetates; D058228:Islet Amyloid Polypeptide; C016456:N(alpha)-fluorenylmethyloxycarbonylamino acids; D009842:Oligopeptides; D013844:Thiazoles; C505976:pseudoproline; C054051:thallium trifluoroacetate; D011392:Proline; D013793:Thallium; D014269:Trifluoroacetic Acid