Biophysics Reports

2018 Vol. 4, No. 5

Cover Story

Through the efforts of Dr. Shizhang Bei, the State Council of China approved the transformation of the Beijing Institute of Experimental Biology into the Institute of Biophysics (IBP), Chinese Academy of Sciences (CAS) on 26th September, 1958. In the sixty years since its establishment, the direction of the Institute of Biophysics has been in line with principles proposed by Dr. Bei:integrate theory with practice, align work with national needs, and strive to reach and surpass global standards. The Institute has attracted a group of outstanding scientists and made many great accomplishments in scientific research, leading and promoting research and development in China on radiobiology, cosmology, cell biology, enzymology, structural biology, membrane biology, neurobiology, biocybernetics, and biophysical engineering. In doing so, it has made an important contribution to the development of the life sciences in China. This special issue of the 60th anniversary of the founding of the Institute of Biophysics aims to further enhance cooperation and communication between the Institute and academic colleagues in the field.

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Animal protein toxins: origins and therapeutic applications

Na Chen, Siqi Xu, Yuhan Zhang, Feng Wang

2018, 4(5): 233-242. doi: 10.1007/s41048-018-0067-x

Abstract(1063)

PDF(108)

Abstract:
Venomous animals on the earth have been found to be valuable resources for the development of therapeutics. Enzymatic and non-enzymatic proteins and peptides are the major components of animal venoms, many of which can target various ion channels, receptors, and membrane transporters. Compared to traditional small molecule drugs, natural proteins and peptides exhibit higher specificity and potency to their targets. In this review, we summarize the varieties and characteristics of toxins from a few representative venomous animals, and describe the components and applications of animal toxins as potential drug candidates in the treatment of human diseases, including cancer, neurodegenerative diseases, cardiovascular diseases, neuropathic pain, as well as autoimmune diseases. In the meantime, there are many obstacles to translate new toxin discovery to their clinical applications. The challenges, strategies, and perspectives in the development of the protein toxin-based drugs are discussed as well.

Targeting tumor cells with antibodies enhances anti-tumor immunity

Zhichen Sun, Yang-Xin Fu, Hua Peng

2018, 4(5): 243-253. doi: 10.1007/s41048-018-0070-2

Abstract(1319)

PDF(66)

Abstract:
Tumor-targeting antibodies were initially defined as a group of therapeutic monoclonal antibodies (mAb) that recognize tumor-specific membrane proteins, block cell signaling, and induce tumor-killing through Fc-driven innate immune responses. However, in the past decade, ample evidence has shown that tumor-targeting mAb (TTmAb) eradicates tumor cells via activation of cytotoxic T cells (CTLs). In this review, we specifically focus on how TTmAbs induce adaptive anti-tumor immunity and its potential in combination therapy with immune cytokines, checkpoint blockade, radiation, and enzymetargeted small molecule drugs. Exploring the mechanisms of these preclinical studies and retrospective clinical data will significantly benefit the development of highly efficient and specific TTmAb-oriented anti-tumor remedies.

Small-animal SPECT/CT imaging of cancer xenografts and pulmonary fibrosis using a ^99mTc-labeled integrin αvβ6-targeting cyclic peptide with improved in vivo stability

Hao Liu, Liquan Gao, Xinhe Yu, Lijun Zhong, Jiyun Shi, Bing Jia, Nan Li, Zhaofei Liu, Fan Wang

2018, 4(5): 254-264. doi: 10.1007/s41048-018-0071-1

Abstract(1584)

PDF(84)

Abstract:
Integrin αvβ6 is expressed at an undetectable level in normal tissues, but is remarkably upregulated during many pathological processes, especially in cancer and fibrosis. Noninvasive imaging of integrin αvβ6 expression using a radiotracer with favorable in vivo pharmacokinetics would facilitate disease diagnosis and therapy monitoring. Through disulfide-cyclized method, we synthesized in this study, a new integrin αvβ6-targeted cyclic peptide (denoted as cHK), and radiolabeled it with ^99mTc. The ability of the resulting radiotracer ^99mTc-HYNIC-cHK to detect integrin αvβ6 expression in pancreatic cancer xenografts and idiopathic pulmonary fibrosis was evaluated using small-animal single-photon emission computed tomography (SPECT)/computed tomography (CT). ^99mTc-HYNIC-cHK showed significantly improved in vivo metabolic stability compared to the linear peptide-based radiotracer ^99mTc-HYNIC-HK. ^99mTc-HYNIC-cHK exhibited similar biodistribution properties to ^99mTc-HYNIC-HK, but the tumorto-muscle ratio was significantly increased (2.99±0.87 vs. 1.82±0.27, P<0.05). High-contrast images of integrin αvβ6-positive tumors and bleomycin-induced fibrotic lungs were obtained by SPECT/CT imaging using ^99mTc-HYNIC-cHK. Overall, our studies demonstrate that ^99mTc-HYNIC-cHK is a promising SPECT radiotracer for the noninvasive imaging of integrin αvβ6 in living subjects.

Raman spectra of the GFP-like fluorescent proteins

Ye Yuan, Dianbing Wang, Jibin Zhang, Ji Liu, Jian Chen, Xian-En Zhang

2018, 4(5): 265-272. doi: 10.1007/s41048-018-0072-0

Abstract(124)

PDF(63)

Abstract:
The objective of the study was to elucidate optical characteristics of the chromophore structures of fluorescent proteins. Raman spectra of commonly used GFP-like fluorescent proteins (FPs) with diverse emission wavelengths (green, yellow, cyan and red), including the enhanced homogenous FPs EGFP, EYFP, and ECFP (from jellyfish) as well as mNeptune (from sea anemone) were measured. High-quality Raman spectra were obtained and many marker bands for the chromophore of the FPs were identified via assignment of Raman spectra bands. We report the presence of a positive linear correlation between the Raman band shift of C₅=C₆ and the excitation energy of FPs, demonstrated by plotting absorption maxima (cm^-1) against the position of the Raman band C₅=C₆ in EGFP, ECFP, EYFP, the anionic chromophore and the neutral chromophore. This study revealed new Raman features in the chromophores of the observed FPs, and may contribute to a deeper understanding of the optical properties of FPs.

Significant expansion and red-shifting of fluorescent protein chromophore determined through computational design and genetic code expansion

Li Wang, Xian Chen, Xuzhen Guo, Jiasong Li, Qi Liu, Fuying Kang, Xudong Wang, Cheng Hu, Haiping Liu, Weimin Gong, Wei Zhuang, Xiaohong Liu, Jiangyun Wang

2018, 4(5): 273-285. doi: 10.1007/s41048-018-0073-z

Abstract(114)

PDF(94)

Abstract:
Fluorescent proteins (FPs) with emission wavelengths in the far-red and infrared regions of the spectrum provide powerful tools for deep-tissue and super-resolution imaging. The development of red-shifted FPs has evoked widespread interest and continuous engineering efforts. In this article, based on a computational design and genetic code expansion, we report a rational approach to significantly expand and red-shift the chromophore of green fluorescent protein (GFP). We applied computational calculations to predict the excitation and emission wavelengths of a FP chromophore harboring unnatural amino acids (UAA) and identify in silico an appropriate UAA, 2-amino-3-(6-hydroxynaphthalen-2-yl)propanoic acid (naphthol-Ala). Our methodology allowed us to formulate a GFP variant (cpsfGFP-66-Naphthol-Ala) with red-shifted absorbance and emission spectral maxima exceeding 60 and 130 nm, respectively, compared to those of GFP. The GFP chromophore is formed through autocatalytic post-translational modification to generate a planar 4-(p-hydroxybenzylidene)-5-imidazolinone chromophore. We solved the crystal structure of cpsfGFP-66-naphthol-Ala at 1.3 Å resolution and demonstrated the formation of a much larger conjugated π-system when the phenol group is replaced by naphthol. These results explain the significant red-shifting of the excitation and emission spectra of cpsfGFP-66-naphthol-Ala.