Amphiphilic conjugates of human brain natriuretic peptide designed for oral delivery: In vitro activity screening

被引：14

作者：

Miller, MA ^{[1
]}

Malkar, NB ^{[1
]}

Severynse-Stevens, D ^{[1
]}

Yarbrough, KG ^{[1
]}

Bednarcik, MJ ^{[1
]}

Dugdell, RE ^{[1
]}

Puskas, ME ^{[1
]}

Krishnan, R ^{[1
]}

James, KD ^{[1
]}

机构：

[1] Nobex Corp, Durham, NC 27713 USA

来源：

BIOCONJUGATE CHEMISTRY | 2006年 / 17卷 / 02期

关键词：

D O I：

10.1021/bc0501000

中图分类号：

Q5 [生物化学];

学科分类号：

071010 ; 081704 ;

摘要：

Congestive heart failure (CHF) is a complex syndrome involving altered neurohormonal levels and impaired cardiac and renal function. In recent years, intravenous administration of exogenous human brain-type natriuretic peptide (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 CHF patients 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 results obtained from hBNP conjugates featuring a variety of rationally designed amphiphilic oligomers. Mapping studies revealed 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. Many monoconjugates retained activity comparable to native peptide and are currently under evaluation in subsequent in vivo screens.

引用

页码：267 / 274

页数：8

共 23 条

[1]

ABUCHOWSKI A, 1977, J BIOL CHEM, V252, P3582

[2]

ABUCHOWSKI A, 1977, J BIOL CHEM, V252, P3578

[3] Oral human brain natriuretic peptide activates cyclic guanosine 3′,5′-monophosphate and decreases mean arterial pressure [J].