Perry Chris C, Ramos-Méndez Jose, Milligan Jamie R
Department of Basic Sciences, School of Medicine, Loma Linda University, 11085 Campus Street, Loma Linda, CA 92350, USA.
Department of Radiation Oncology, University of California San Francisco, 1600 Divisadero Street, San Francisco, CA 94115, USA.
Radiat Phys Chem Oxf Engl 1993. 2020 Jan;166. doi: 10.1016/j.radphyschem.2019.108521. Epub 2019 Oct 10.
The amino acid derivative 4-borono--phenylalanine (BPA) has been used in the radiation medicine technique boron neutron capture therapy (BNCT). Here we have characterized its interaction with DNA when incorporated into a positively charged hexa--arginine peptide. This ligand binds strongly to DNA and induces its condensation, an effect which is attenuated at higher ionic strengths. The use of an additional tetra--arginine ligand enables the preparation of a DNA condensate in the presence of a negligible concentration of unbound boron. Under these conditions, Monte Carlo simulation indicates that >85% of energy deposition events resulting from thermal neutron irradiation derive from boron fission. The combination of experimental model systems and simulations that we describe here provides a valuable tool for accurate track structure modeling of the DNA damage produced by the high LET particles involved in BNCT.
氨基酸衍生物4-硼代-L-苯丙氨酸（BPA）已被应用于放射医学技术——硼中子俘获疗法（BNCT）。在此，我们已对其掺入带正电荷的六聚精氨酸肽时与DNA的相互作用进行了表征。这种配体与DNA强烈结合并诱导其凝聚，在较高离子强度下这种效应会减弱。使用额外的四聚精氨酸配体能够在未结合硼的浓度可忽略不计的情况下制备DNA凝聚物。在这些条件下，蒙特卡罗模拟表明，热中子辐照产生的能量沉积事件中>85%源自硼裂变。我们在此描述的实验模型系统与模拟的结合为准确模拟BNCT中涉及的高传能线密度粒子所产生的DNA损伤的径迹结构提供了一种有价值的工具。
