Department of Chemistry, University of California, One Shields Avenue, Davis, CA, 95616, USA.
Chembiochem. 2019 Oct 1;20(19):2447-2453. doi: 10.1002/cbic.201900172. Epub 2019 May 9.
The connecting peptide (C-peptide) has received increased attention for its potential therapeutic effects in ameliorating illnesses such as kidney disease and diabetes. Although the mechanism of C-peptide signaling remains elusive, evidence supports its internalization and intracellular function. Emerging research is uncovering the diverse biological roles metals play in controlling and affecting the function of bioactive peptides. The work presented herein investigates interactions between C-peptide and first-row d-block transition metals, as well as their effects on C-peptide internalization into cells. Through spectroscopic techniques, it is demonstrated that Cr , Cu , and Zn bind to C-peptide with differing stoichiometries and biologically relevant affinities. In addition, metal binding elicits both subtle changes in secondary structure and inhibits adoption of an α-helical character in environments where the dielectric constants are reduced. This study shows how metal ions can modulate peptide hormone activity through subtle structural changes to disrupt cellular uptake.
连接肽（C 肽）因其在改善肾脏疾病和糖尿病等疾病方面的潜在治疗效果而受到越来越多的关注。尽管 C 肽信号转导的机制尚不清楚，但有证据表明其具有内化和细胞内功能。新兴的研究揭示了金属在控制和影响生物活性肽功能方面的多种生物学作用。本文研究了 C 肽与第一过渡金属 d 区元素之间的相互作用，以及它们对 C 肽进入细胞内化的影响。通过光谱技术，证明 Cr、Cu 和 Zn 以不同的化学计量比和具有生物学相关性的亲和力与 C 肽结合。此外，金属结合会引起二级结构的细微变化，并抑制在介电常数降低的环境中形成 α-螺旋特征。这项研究表明，金属离子如何通过细微的结构变化来调节肽激素活性，从而破坏细胞摄取。
