Conversion of Proteins to Diazeniumdiolate-Based Nitric Oxide Donors
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- 作者：Joseph A. Hrabie ; Joseph E. Saavedra ; Peter P. Roller ; Garry J. Southan ; and Larry K. Keefer
- 刊名：Bioconjugate Chemistry
- 出版年：1999
- 出版时间：September 1999
- 年：1999
- 卷：10
- 期：5
- 页码：838 - 842
- 全文大小：92K
- 年卷期：v.10,no.5(September 1999)
- ISSN：1520-4812
文摘
Michael reaction of the methoxymethyl-protected monodiazeniumdiolate of piperazine (MOM-PIPERAZI/NO) with 4-maleimidobutyric acid followed by its conversion to the N-hydroxy-succinimidoester produces a reagent capable of transferring the nitric oxide (NO)-donating diazeniumdiolate groupto the terminal amines of the lysine residues contained in proteins. The reagent has been used toproduce diazeniumdiolated bovine serum albumin (D-BSA) and diazeniumdiolated human serumalbumin (D-HSA) containing 22 and 19 modified lysyl groups, respectively. Upon dissolution in pH7.4 phosphate buffer at 37 
C, these albumin derivatives gradually released all of their contained NO(approximately 40 mol/mol of protein) with initial rates of about 30-40 pmol/min/mg and half-liveson the order of 3 weeks. This methodology is now available for use in exploiting the unique specificmetabolic interactions of proteins to target NO therapy to specific physiological processes in vivo.
C, these albumin derivatives gradually released all of their contained NO(approximately 40 mol/mol of protein) with initial rates of about 30-40 pmol/min/mg and half-liveson the order of 3 weeks. This methodology is now available for use in exploiting the unique specificmetabolic interactions of proteins to target NO therapy to specific physiological processes in vivo.