Amphiphilic Conjugates of Human Brain Natriuretic Peptide Designed for Oral Delivery: In Vitro Activity Screening
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- 作者：Mark A. Miller ; Navdeep B. Malkar ; Diana Severynse-Stevens ; Kevin G. Yarbrough ; Mark J. Bednarcik ; Robert E. Dugdell ; Monica E. Puskas ; Radha Krishnan ; and Kenneth D. James
- 刊名：Bioconjugate Chemistry
- 出版年：2006
- 出版时间：March 2006
- 年：2006
- 卷：17
- 期：2
- 页码：267 - 274
- 全文大小：199K
- 年卷期：v.17,no.2(March 2006)
- ISSN：1520-4812
文摘
Congestive heart failure (CHF) is a complex syndrome involving altered neurohormonal levels and impairedcardiac and renal function. In recent years, intravenous administration of exogenous human brain-type natriureticpeptide (hBNP) has become an important therapy in treating patients with acutely decompensated CHF. However,reports during the past year suggest that hBNP could play a prominent role in the chronic treatment of CHFpatients as well. We are currently developing conjugates of hBNP suitable for oral delivery to provide a patient-friendly treatment option for chronic heart failure patients. In this report, we present in vitro activity resultsobtained from hBNP conjugates featuring a variety of rationally designed amphiphilic oligomers. Mapping studiesrevealed that the hydrophobic/hydrophilic balance of the oligomer impacted the regioselectivity of conjugation.Additionally, the regiochemistry and extent of conjugation had a significant impact on activity. Manymonoconjugates retained activity comparable to native peptide and are currently under evaluation in subsequentin vivo screens.