Synthesis and evaluation of photolabile insulin prodrugs

Lian Sheng Li; Jennie L. Babendure; Subhash C. Sinha; Jerrold M. Olefsky; Richard A. Lerner

doi:10.1016/j.bmcl.2005.05.112

Synthesis and evaluation of photolabile insulin prodrugs

Lian Sheng Li, Jennie L. Babendure, Subhash C. Sinha, Jerrold M. Olefsky, Richard A. Lerner

Research output: Contribution to journal › Article › peer-review

3 Scopus citations

Abstract

We have developed two photolabile insulin prodrugs, insulin-2P and insulin-3P. These prodrugs were synthesized by protecting GlyA1 (N ^αA1), and one or both of the PheB1 (N^αB1) and LysB29 (N^εB29) amino groups in insulin using 5′-(α-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.

Original language	English (US)
Pages (from-to)	3917-3920
Number of pages	4
Journal	Bioorganic and Medicinal Chemistry Letters
Volume	15
Issue number	17
DOIs	https://doi.org/10.1016/j.bmcl.2005.05.112
State	Published - Sep 1 2005
Externally published	Yes

Keywords

Diabetes
Insulin
Photolysis
Prodrug
Ultraviolet

ASJC Scopus subject areas

Biochemistry
Molecular Medicine
Molecular Biology
Pharmaceutical Science
Drug Discovery
Clinical Biochemistry
Organic Chemistry

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10.1016/j.bmcl.2005.05.112

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title = "Synthesis and evaluation of photolabile insulin prodrugs",

abstract = "We have developed two photolabile insulin prodrugs, insulin-2P and insulin-3P. These prodrugs were synthesized by protecting GlyA1 (N αA1), and one or both of the PheB1 (NαB1) and LysB29 (NεB29) amino groups in insulin using 5′-(α-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 = "Diabetes, Insulin, Photolysis, Prodrug, Ultraviolet",

author = "Li, {Lian Sheng} and Babendure, {Jennie L.} and Sinha, {Subhash C.} and Olefsky, {Jerrold M.} and Lerner, {Richard A.}",

note = "Funding Information: Financial supports from the Skaggs Institute for Chemical Biology (S.C.S. and R.A.L.) are gratefully acknowledged. This work was also supported in part by NIH Grant DK-33651 (J.L.B. and J.M.O.). This is manuscript number 17354-MB from The Scripps Research Institute. ",

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doi = "10.1016/j.bmcl.2005.05.112",

language = "English (US)",

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T1 - Synthesis and evaluation of photolabile insulin prodrugs

AU - Li, Lian Sheng

AU - Babendure, Jennie L.

AU - Sinha, Subhash C.

AU - Olefsky, Jerrold M.

AU - Lerner, Richard A.

N1 - Funding Information: Financial supports from the Skaggs Institute for Chemical Biology (S.C.S. and R.A.L.) are gratefully acknowledged. This work was also supported in part by NIH Grant DK-33651 (J.L.B. and J.M.O.). This is manuscript number 17354-MB from The Scripps Research Institute.

PY - 2005/9/1

Y1 - 2005/9/1

N2 - We have developed two photolabile insulin prodrugs, insulin-2P and insulin-3P. These prodrugs were synthesized by protecting GlyA1 (N αA1), and one or both of the PheB1 (NαB1) and LysB29 (NεB29) amino groups in insulin using 5′-(α-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.

AB - We have developed two photolabile insulin prodrugs, insulin-2P and insulin-3P. These prodrugs were synthesized by protecting GlyA1 (N αA1), and one or both of the PheB1 (NαB1) and LysB29 (NεB29) amino groups in insulin using 5′-(α-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.

KW - Diabetes

KW - Insulin

KW - Photolysis

KW - Prodrug

KW - Ultraviolet

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JO - Bioorganic and Medicinal Chemistry Letters

JF - Bioorganic and Medicinal Chemistry Letters

IS - 17

ER -

Synthesis and evaluation of photolabile insulin prodrugs

Abstract

Keywords

ASJC Scopus subject areas

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