Synthesis and evaluation of photolabile insulin prodrugs |
| |
Authors: | Li Lian-Sheng Babendure Jennie L Sinha Subhash C Olefsky Jerrold M Lerner Richard A |
| |
Affiliation: | The Skaggs Institute for Chemical Biology and Department of Molecular Biology, The Scripps Research Institute, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA. |
| |
Abstract: | We have developed two photolabile insulin prodrugs, insulin-2P and insulin-3P. These prodrugs were synthesized by protecting GlyA1 (N(alphaA1)), and one or both of the PheB1 (N(alphaB1)) and LysB29 (N(epsilonB29)) amino groups in insulin using 5'-(alpha-methyl-nitro-piperonyl)oxy-carbonyl as the protecting group. These insulin prodrugs were efficiently activated by exposure to longwave UV light to produce insulin quantitatively. Using 2-deoxyglucose uptake assays, both di- and tri-protected compounds were less active than native insulin in the protected state, and showed comparable activity to native insulin upon photoactivation. |
| |
Keywords: | |
本文献已被 ScienceDirect PubMed 等数据库收录! |
|