Fast Fmoc synthesis of hAmylin1-37 with pseudoproline assisted on-resin disulfide formation. |
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Authors: | Karen Page Christina A Hood Hirendra Patel German Fuentes Mahendra Menakuru Jae H Park |
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Affiliation: | Department of Chemistry, Protein Technologies Inc., Tucson, Arizona, 4675 South Coach Drive, Tucson, Arizona 85714, USA. |
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Abstract: | 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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Keywords: | fast Fmoc SPPS human amylin1–37 pseudoproline dipeptide disulfide bridge |
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