Morisco Anna, Accardo Antonella, Gianolio Eliana, Tesauro Diego, Benedetti Ettore, Morelli Giancarlo
Department of Biological Sciences, CIRPeB, University of Naples "Federico II" and IBB CNR, Via Mezzocannone 16, 80134 Naples, Italy.
J Pept Sci. 2009 Mar;15(3):242-50. doi: 10.1002/psc.1087.
New amphiphilic monomers (OCA-DTPAGlu and OCA-DOTA) containing, in the same molecule, three different functions: (i) the chelating agent (DTPAGlu or DOTA) able to coordinate gadolinium ion, (ii) the octreotide bioactive peptide able to target somatostatin receptors, and (iii) a hydrophobic moiety with two 18-carbon atoms alkyl chains have been designed and synthesized by solid-phase methods. The novel amphiphilic monomers aggregate, in water solution, giving stable micelles at very low concentration (cmc values of 2.3 x 10(-6) mol kg(-1) and 2.5 x 10(-6) mol kg(-1) for OCA-DTPAGlu and OCA-DOTA, respectively) as confirmed by fluorescence spectroscopy. Fluorescence studies and circular dichroism experiments indicate, for the two compounds as well as for their gadolinium complexes (OCA-DOTA(Gd) and OCA-DTPAGlu(Gd)), the complete exposure of octreotide on the micelle surface, and the predominant presence of an antiparallel beta-sheet peptide conformation characterized by a beta-like turn. The high relaxivity value (r(1p) = 13.9 mM(-1) s(-1) at 20 MHz and 25 degrees C), measured for micelles obtained by the gadolinium complex OCA-DTPAGlu(Gd), indicates these aggregates as promising target-selective magnetic resonance imaging (MRI) contrast agents.
新型两亲性单体（OCA-DTPAGlu和OCA-DOTA）在同一分子中含有三种不同功能：（i）能够配位钆离子的螯合剂（DTPAGlu或DOTA）；（ii）能够靶向生长抑素受体的奥曲肽生物活性肽；（iii）带有两条18个碳原子烷基链的疏水部分。通过固相方法设计并合成了这些新型两亲性单体。新型两亲性单体在水溶液中聚集，在极低浓度下形成稳定的胶束（OCA-DTPAGlu和OCA-DOTA的临界胶束浓度分别为2.3×10⁻⁶mol kg⁻¹和2.5×10⁻⁶mol kg⁻¹），荧光光谱证实了这一点。荧光研究和圆二色性实验表明，对于这两种化合物及其钆配合物（OCA-DOTA(Gd)和OCA-DTPAGlu(Gd)），奥曲肽完全暴露在胶束表面，并且主要存在以β样转角为特征的反平行β-折叠肽构象。通过钆配合物OCA-DTPAGlu(Gd)得到的胶束在20MHz和25℃下测得的高弛豫率值（r₁p = 13.9 mM⁻¹ s⁻¹）表明这些聚集体有望成为靶向选择性磁共振成像（MRI）造影剂。
