Micellar nanomedicine of human neuropeptide Y.
Micellar nanomedicine of human neuropeptide Y.
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DOI：
10.1016/j.nano.2011.01.004
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发表时间：
2011-08
影响因子：
5.4
通讯作者：
Oenyueksel, Hayat
中科院分区：
文献类型：
--
作者：
Kuzmis, Antonina;Lim, Sok Bee;Desai, Esha;Jeon, Eunjung;Lee, Bao-Shiang;Rubinstein, Israel;Oenyueksel, Hayat
关键词：
人神经肽Y（neuropeptide Y，NPY）是一种重要的生物活性物质，具有多种生理功能，可用于某些疾病的治疗。然而，快速（分钟）酶降解和失活的神经肽Y排除了它作为一种药物的发展。因此，我们确定了NPY与生物相容性和可生物降解的空间稳定磷脂胶束（SSM）的自缔合是否提高了其稳定性和生物活性。我们发现，在生理盐水中，NPY自发聚集，而在SSM的存在下，它与胶束作为单体自缔合。三个NPY分子在饱和时与一个SSM自缔合。该过程使肽稳定在α-螺旋构象，消除其被二肽基肽酶-4降解，并增强NPY诱导的对SK-N-MC细胞中cAMP加工的抑制。总的来说，这些数据表明，NPY与SSM的自缔合稳定并保护活性单体构象的肽，从而在体外放大其生物活性。我们建议进一步发展神经肽Y在SSM作为一种新型的，长效的纳米药物。
Human neuropeptide Y (NPY) is an important biologics that regulates multitude of physiological functions and could be amenable to therapeutic manipulations in certain disease states. However, rapid (minutes) enzymatic degradation and inactivation of NPY precludes its development as a drug. Accordingly, we determined whether self-association of NPY with biocompatible and biodegradable sterically stabilized phospholipid micelles (SSM) improves its stability and bioactivity. We found that in saline NPY spontaneously aggregates whereas in the presence of SSM it self-associates with the micelles as monomers. Three NPY molecules self-associate with one SSM at saturation. This process stabilizes the peptide in α-helix conformation, abrogates its degradation by dipeptidyl peptidase-4 and potentiates NPY-induced inhibition of cAMP elaboration in SK-N-MC cells. Collectively, these data indicate that self-association of NPY with SSM stabilizes and protects the peptide in active monomeric conformation, thereby amplifying its bioactivity in vitro. We propose further development of NPY in SSM as a novel, long-acting nanomedicine.
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神经肽Y基因敲除小鼠揭示了NPY在骨骼质量与体重的协调中的中心作用。
影响因子：
3.7
作者：
Baldock PA;Lee NJ;Driessler F;Lin S;Allison S;Stehrer B;Lin EJ;Zhang L;Enriquez RF;Wong IP;McDonald MM;During M;Pierroz DD;Slack K;Shi YC;Yulyaningsih E;Aljanova A;Little DG;Ferrari SL;Sainsbury A;Eisman JA;Herzog H
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影响因子：
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通讯作者：
Önyüksel, H
影响因子：
3
作者：
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von Hoersten, Stephan
影响因子：
5.6
作者：
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通讯作者：
Zerbe, O
影响因子：
4.4
作者：
Laviano, Alessandro;Inui, Akio;Rossi Fanelli, Filippo
通讯作者：
Rossi Fanelli, Filippo