Metal ions as cofactors for aggregation of therapeutic peptide salmon calcitonin.
Metal ions as cofactors for aggregation of therapeutic peptide salmon calcitonin.
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DOI：
10.1021/ic202604v
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发表时间：
2012-05
影响因子：
4.6
通讯作者：
N. Rastogi;K. Mitra;Dinesh Kumar;R. Roy
中科院分区：
文献类型：
--
作者：
N. Rastogi;K. Mitra;Dinesh Kumar;R. Roy
多价金属离子(Cu(2+)/Zn（2+)/Al(3+)）对鲑鱼降钙素（sCT）聚集的影响（sCT是一种用于治疗骨质疏松症和佩吉特病的治疗肽）已经在体外使用NMR（溶液态和固态），TEM， tht荧光和FT-IR光谱进行了研究。总的来说，各种结果表明，金属离子诱导的肽的构象转变——主要是向β-片的转变——促进了溶液中sCT的聚集。首先，用溶液核磁共振检查了肽与金属离子之间的相互作用。在此之后，使用TEM，固态核磁共振和FT-IR光谱进行了降钙素聚集体的形成和表征。TEM和tht荧光结果显示，与Cu（2+）和Zn（2+）金属离子（在水环境中）孵育的sCT肽形成球状聚集体，与Al（3+）离子孵育的sCT肽形成原纤维。固态NMR和FT-IR研究显示，与单体sCT相比，sCT聚集体（在这些金属离子存在下形成）中存在大量β-片含量，表明金属结合伴随着构象变化。在与体内金属离子(Cu(2+)/Zn（2+)/Al(3+)）异常积累（即异常金属离子稳态）相关的生理病理条件下（即异常金属离子稳态）处方这种药物肽时，本研究变得至关重要。
The effects of multivalent metal ions (Cu(2+)/Zn(2+)/Al(3+)) on the aggregation of salmon calcitonin (sCT)--a therapeutic peptide used worldwide in the treatment of osteoporosis and Paget's disease--have been studied in vitro using NMR (both solution state and solid state), TEM, ThT-fluorescence, and FT-IR spectroscopy. Overall, the various results indicated that the metal-ions-induced conformational transitions in the peptide--mostly toward the β-sheet--facilitate the aggregation of sCT in solution. First, the solution NMR has been used to check the interaction between the peptide and the metal ions. Following this, the formation and characterization of calcitonin aggregates has been performed using TEM, solid state NMR, and FT-IR spectroscopy. The TEM and ThT-fluorescence results revealed that the sCT peptide incubated with Cu(2+) and Zn(2+) metal ions (in aqueous environment) forms globular aggregates, while that with Al(3+) ions forms fibrils. The solid state NMR and FT-IR studies revealed the presence of a substantial amount of β-sheet content in sCT aggregates (formed in the presence of these metal ions) compared to the monomeric sCT, indicating that the metal binding is concomitant with conformational changes. The present study becomes crucial while prescribing this drug peptide under physio-pathological conditions associated with an abnormal accumulation of metal ions (Cu(2+)/Zn(2+)/Al(3+)) in the body (i.e., abnormal metal ion homeostasis).