蛋白質和蛋白質間的交互作用廣泛地調控龐大的生物機制，包含細胞與細胞間黏合與辨識、細胞間訊息傳遞、病毒或細菌對細胞的傳染、產生免疫反應。然而，闡釋蛋白質和蛋白質間的交互作用的過程是艱難且耗時的，且經常無法顯示清楚的分析結果。尤其又以探討凝集素和醣蛋白間的作用力最為艱鉅，此乃由於醣體與凝集素間作用力為非共價、可逆的鍵結以及微弱親合力。
本論文基於配位基輔助拓印探針的方法，在此簡稱為”LIP”，而發展凝集素探針以用於後續探討凝集素與醣蛋白間之交聯作用；於此研究，先以植物性凝集素Ricinus communis agglutinin 120(RCA120)和B細胞上的跨膜受體cluster of differentiation-22(CD22)應用於第一代凝集素探針之模型蛋白以驗證此策略之可行性，再以recombinant human Siglec-7 Fc chimera protein (Siglec-7-Fc)做為第二代凝集素探針修飾之目標蛋白；LIP的整個架構主要利用amide bond formation化學有效地合成含有多功能基團小分子探針LIP，其中LIP的設計含有五個部分及其功能，以醣體做為配位基將小分子導向凝集素之碳水化合物鍵結位點，再以紫外光激發光敏感基diazirine，於凝集素表面形成共價鍵結，同時啟動光敏斷裂基團之異構化(E-Z isomerization)形成中間體，再以生物素(biotin) 做為純化基團之後，進一步觸發光敏斷裂基團的中間體斷裂，於結合位點上移除醣體和生物素，而將炔基建構於醣結合位點附近以利後續用於生物正交點擊化學反應(Bioorthogonal click chemistry)，以用於合成不同種類之凝集素探針。
本論文以三官能基團探針(含有疊氮基團及光敏感基及生物素)、含疊氮基之環境敏感探針經由Copper(I)-catalyzed Alkyne-Azide Cycloaddition (CuAAC) 反應於炔基化的凝集素上進行修飾以建構凝集素探針，分別應用於凝集素-醣蛋白之交聯反應及免洗滌之HeLa細胞即時監控顯影，最後，我們將修飾炔基化的Siglec-7-Fc與含疊氮基之阿黴素(Doxorubicin)結合做為凝集素藥物，應用於癌細胞抑制實驗中，並藉由MTT assay分析HeLa細胞的活性，結果顯示Siglec-7-Fc-drug可抑制HeLa細胞生長，並以HEK 293細胞做為對照組，證明此凝集素藥物進入細胞之途徑首先為醣蛋白與凝集素之交互作用而進入。
於上述研究過程中，亦發展出以抗癌藥物博來黴素(Bleomycin)之化學結構上的甘露糖部分做為配位基，結合環境敏感小分子所形成之探針以研究醣體與MCF-7膜蛋白之交聯作用，並分別以配位基為甘露糖及半乳醣之環境敏感探針做為對照組，以證明博來黴素經由通過MCF-7膜上之受體進入細胞而非經由小分子擴散(diffusion)進入細胞。

Protein-protein interactions (PPIs) modulate many biological processes. However, elucidation of PPI events is notoriously difficult and time consuming and often yields complex and unclear results. Lectin-glycoprotein interactions are especially difficult to study due to the noncovalent nature of the interactions and inherently low binding affinities of proteins to glycan ligands on glycoproteins. Here, we report a “ligand-assisted imprinting probe” (LIP)-based approach to fabricate protein probes for elucidating protein-glycoprotein interactions. The LIP was designed with dual photoactivatable groups for introduction of a site-specific clickable alkyne handle proximal to the carbohydrate-binding pocket of the lectin, namely, Ricinus communis agglutinin 120, cluster of differentiation-22(CD22) and recombinant human Siglec-7 Fc chimera protein (Siglec-7-Fc). In a proof-of-principle study, alkynylated RCA120 was conjugated with a photoreactive diazirine crosslinker and an environment-sensitive fluorophore by a bioorthogonal click reaction for anchoring the glycoprotein ovalbumin in solution and detecting endogenously expressed glycoproteins on HeLa cells, respectively. An environmental sensor was also site-specifically conjugated on the surface of CD22 near the carbohydrate binding site for no-wash imaging of living HeLa cell. We anticipate that the fabrication of this protein probe will accelerate the discovery of novel PPIs.
Furthermore, we synthesized a second generation LIP for the fabrication of Siglec-7-Fc-drug conjugates via click reaction with azido-doxorubicin and application on the inhibition of HeLa cells viability through the analysis of MTT assay. To validate the Siglec-7-Fc-drug conjugates internalized into HeLa cells through interaction with glycoprotein on the highly expressed sialosides of HeLa cells membrane, HEK 293 cells with low expressed sialosides was used as a control and treated with Siglec-7-Fc-drug conjugates. The result displayed that the glycoprotein on HeLa cells have carbohydrate ligand to bind the carbohydrate binding site of Siglec-7-Fc and doxorubicin can be released in the HeLa cell to further inhibit the viability of cells.
In the application process of lectin probes, we also developed another kind of ligand-directed environmental probes. One of the ligand is the mannose part of bleomycin which is an anti-cancer drug. Other two probes are mannose and galactose as the ligands in separate. We apply these carbohydrate probes to investigate the bleomycin receptor on the membrane of MCF-7. This research result have revealed that there are some feasible receptors interacted with the carbohydrate of bleomycin to internalize into the MCF-7 cells rather than the cellular process by diffusion.

參考文獻
1. Scott, D. E.; Bayly, A. R.; Abell, C.; Skidmore, J. Small molecules, big targets: drug discovery faces the protein-protein interaction challenge. Nat. Rev. Drug Discovery 2016, 15, 533-550.
2. Takaoka, Y.; Ojida, A.; Hamachi, I. Protein organic chemistry and applications for labeling and engineering in live-cell systems. Angew. Chem., Int. Ed. 2013, 52, 4088-4106.
3. Sakurai, K.; Ozawa, S.; Yamaguchi, T. Photoaffinity labeling studies of the carbohydrate-binding proteins with different affinities. Bioorg. Med. Chem. 2015, 23, 5319-5325.
4. Tamura, T.; Ueda, T.; Goto, T.; Tsukidate, T.; Shapira, Y.; Nishikawa, Y.; Fujisawa, A.; Hamachi, I. Rapid labelling and covalent inhibition of intracellular native proteins using ligand-directed N-acyl-N-alkyl sulfonamide. Nat. Commun. 2018, 9, 1870.
5. Kunishima, M.; Nakanishi, S.; Nishida, J.; Tanaka, H.; Morisaki, D.; Hioki, K.; Nomoto, H. Convenient modular method for affinity labeling (MoAL method) based on a catalytic amidation. Chem. Commun. 2009, 37, 5597-5599.
6. Murale, D. P.; Hong, S. C.; Haque, M. M.; Lee, J. S. Photo-affinity labeling (PAL) in chemical proteomics: a handy tool to investigate protein-protein interactions (PPIs). Proteome Sci. 2016, 15, 14-47.
7. Site-Specific Protein Labeling: Methods and Protocols; Methods in Molecular Biology; Gautier, A., Hinner, M. J., Eds.; Springer: New York, 2015.
8. Chang, T.-C.; Lai, C.-H.; Chien, C.-W.; Liang, C.-F.; Adak, A. K.; Chuang, Y.-J.; Chen, Y.-J.; Lin, C.-C. Synthesis and Evaluation of a Photoactive Probe with a Multivalent Carbohydrate for Capturing Carbohydrate–Lectin Interactions. Bioconjugate Chem. 2013, 24, 1895-1906.
9. Chang, T.-C.; Adak, A. K.; Lin, T.-W.; Li, P.-J.; Chen, Y.-J.; Lai, C.-H.; Liang, C.-F.; Chen, Y.-J.; Lin, C.-C. A photo-cleavable biotin affinity tag for the facile release of a photo-crosslinked carbohydrate-binding protein. Bioorg. Med. Chem. 2016, 24, 1216-1224.
10. Varki, A. Evolutionary forces shaping the golgi glycosylation machinery: Why cell surface glycans are universal to living cells. Cold Spring Harb. Perspect. Biol. 2011, 3, a005462.
11. Maverakis, E.; Kim, K.; Shimoda, M.; Gershwin, M. E.; Patel, F.; Wilken, R.; Raychaudhuri, S.; Ruhaak, L. R.; Lebrilla, C. B. Glycans in the immune system and The Altered Glycan Theory of Autoimmunity: A critical review. J. Autoimmun. 2015, 57, 1-13.
12. McMichael, A. J.; Borrow, P.; Tomaras, G. D.; Goonetilleke, N.; Haynes, B. F. The immune response during acute HIV-1 infection: clues for vaccine development. Nat. Rev. Immunol. 2010, 10, 11-23.
13. Christiansen, M. N.; Chik, J.; Lee, L.; Anugraham, M.; Abrahams, J. L.; Packer, N. H. Cell surface protein glycosylation in cancer. Proteomics 2014, 14, 525-546.
14. Pearce, O. M.; Laubli, H. Sialic acids in cancer biology and immunity. Glycobiology 2016, 26, 111-128.
15. Reis, C. A.; Osorio, H.; Silva, L.; Gomes, C.; David, L. Alterations in glycosylation as biomarkers for cancer detection. J. Clin. Pathol. 2010, 63, 322-329.
16. Bull, C.; Stoel, M. A.; den Brok, M. H.; Adema, G. J. Sialic acids sweeten a tumor's life. Cancer Res. 2014, 74, 3199-3204.
17. Almaraz, R. T.; Tian, Y.; Bhattarcharya, R.; Tan, E.; Chen, S. H.; Dallas, M. R.; Chen, L.; Zhang, Z.; Zhang, H.; Konstantopoulos, K.; Yarema, K. J. Metabolic flux increases glycoprotein sialylation: implications for cell adhesion and cancer metastasis. Mol. Cell. Proteomics 2012, 11, M112 017558.
18. Uemura, T.; Shiozaki, K.; Yamaguchi, K.; Miyazaki, S.; Satomi, S.; Kato, K.; Sakuraba, H.; Miyagi, T. Contribution of sialidase NEU1 to suppression of metastasis of human colon cancer cells through desialylation of integrin beta4. Oncogene 2009, 28, 1218-1229.
19. Shiozaki, K.; Yamaguchi, K.; Takahashi, K.; Moriya, S.; Miyagi, T. Regulation of sialyl Lewis antigen expression in colon cancer cells by sialidase NEU4. J. Biol. Chem. 2011, 286, 21052-21061.
20. Becker, D. J.; Lowe, J. B. Fucose: biosynthesis and biological function in mammals. Glycobiology 2003, 13, 41R-53R.
21. Lin, T.-W.; Chang, H.-T.; Chen, C.-H.; Chen, C.-H.; Lin, S.-W.; Hsu, T.-L.; Wong, C.-H. Galectin-3 binding protein and galectin-1 interaction in breast cancer cell aggregation and metastasis. J. Am. Chem. Soc. 2015, 137, 9685-9693.
22. Takeda, Y.; Shinzaki, S.; Okudo, K.; Moriwaki, K.; Murata, K.; Miyoshi, E. Fucosylated haptoglobin is a novel type of cancer biomarker linked to the prognosis after an operation in colorectal cancer. Cancer 2012, 118, 3036-3043.
23. Fujita, K.; Shimomura, M.; Uemura, M.; Nakata, W.; Sato, M.; Nagahara, A.; Nakai, Y.; Takamatsu, S.; Miyoshi, E.; Nonomura, N. Serum fucosylated haptoglobin as a novel prognostic biomarker predicting high‐Gleason prostate cancer. Prostate 2014, 74, 1052-1058.
24. Kuno, A.; Uchiyama, N.; Koseki-Kuno, S.; Ebe, Y.; Takashima, S.; Yamada, M.; Hirabayashi, J. Evanescent-field fluorescence-assisted lectin microarray: a new strategy for glycan profiling. Nat. Methods 2005, 2, 851-856.
25. Hayashi, T.; Sun, Y.; Tamura, T.; Kuwata, K.; Song, Z.; Takaoka, Y.; Hamachi, I. Semisynthetic lectin-4-dimethylaminopyridine conjugates for labeling and profiling glycoproteins on live cell surfaces. J. Am. Chem. Soc. 2013, 135, 12252-12258.
26. Rabinovich, G. A.; Croci, D. O. Regulatory circuits mediated by lectin-glycan interactions in autoimmunity and cancer. Immunity 2012, 36, 322-335.
27. van Kooyk, Y.; Rabinovich, G. A. Protein-glycan interactions in the control of innate and adaptive immune responses. Nat. Immunol. 2008, 9, 593-601.
28. Crocker, P. R.; Varki, A. Siglecs in the immune system. Immunology 2001, 103, 137-145.
29. Rabinovich, G. A.; Toscano, M. A.; Jackson, S. S.; Vasta, G. R. Functions of cell surface galectin-glycoprotein lattices. Curr. Opin. Struct. Biol. 2007, 17, 513-520.
30. Leffler, H.; Carlsson, S.; Hedlund, M.; Qian, Y.; Poirier, F. Introduction to galectins. Glycoconj. J. 2004, 19, 433-440.
31. Figdor, C. G.; van Kooyk, Y.; Adema, G. J. C-type lectin receptors on dendritic cells and Langerhans cells. Nat. Rev. Immunol. 2002, 2, 77-84.
32. Morris, K. N.; Wool, I. G. Determination by systematic deletion of the amino acids essential for catalysis by ricin A chain. Proc. Natl. Acad. Sci. U. S. A. 1992, 89, 4869-4873.
33. Szewczak, A. A.; Moore, P. B.; Chang, Y. L.; Wool, I. G. The conformation of the sarcin/ricin loop from 28S ribosomal RNA. Proc. Natl. Acad. Sci. U. S. A. 1993, 90, 9581-9585.
34. Itakura, Y.; Nakamura-Tsuruta, S.; Kominami, J.; Sharon, N.; Kasai, K.; Hirabayashi, J. Systematic comparison of oligosaccharide specificity of Ricinus communis agglutinin I and Erythrina lectins: a search by frontal affinity chromatography. J. Biochem. 2007, 142, 459-469.
35. Rutenber, E.; Robertus, J. D. Structure of ricin B-chain at 2.5 A resolution. Proteins 1991, 10, 260-269.
36. Wu, A. M.; Wu, J. H.; Singh, T.; Lai, L. J.; Yang, Z.; Herp, A. Recognition factors of Ricinus communis agglutinin 1 (RCA(1)). Mol. Immunol. 2006, 43, 1700-1715.
37. You, W.-K.; Kasman, I.; Hu-Lowe, D. D.; McDonald, D. M. Ricinus communis Agglutinin I Leads to Rapid Down-Regulation of VEGFR-2 and Endothelial Cell Apoptosis in Tumor Blood Vessels. Am. J. Pathol. 2010, 176, 1927-1940.
38. Rana, M.; Dhamija, H.; Prashar, B.; Sharma, S. Ricinus communis L. - A review. Int. J. Pharmtech Res. 2012, 4, 1706-1711.
39. Crocker, P. R.; Paulson, J. C.; Varki, A. Siglecs and their roles in the immune system. Nat. Rev. Immunol. 2007, 7, 255-266.
40. Delputte, P. L.; Van Gorp, H.; Favoreel, H. W.; Hoebeke, I.; Delrue, I.; Dewerchin, H.; Verdonck, F.; Verhasselt, B.; Cox, E.; Nauwynck, H. J. Porcine sialoadhesin (CD169/Siglec-1) is an endocytic receptor that allows targeted delivery of toxins and antigens to macrophages. PLoS One 2011, 6, e16827.
41. Izquierdo-Useros, N.; Lorizate, M.; McLaren, P. J.; Telenti, A.; Krausslich, H. G.; Martinez-Picado, J. HIV-1 Capture and Transmission by Dendritic Cells: The Role of Viral Glycolipids and the Cellular Receptor Siglec-1. PLoS Pathog. 2014, 10, e1004146.
42. Kiwamoto, T.; Kawasaki, N.; Paulson, J. C.; Bochner, B. S. Siglec-8 as a drugable target to treat eosinophil and mast cell-associated conditions. Pharmacol. Ther. 2012, 135, 327-336.
43. Pillai, S.; Netravali, I. A.; Cariappa, A.; Mattoo, H. Siglecs and immune regulation. Annu. Rev. Immunol. 2012, 30, 357-392.
44. Poe, J. C.; Fujimoto, Y.; Hasegawa, M.; Haas, K. M.; Miller, A. S.; Sanford, I. G.; Bock, C. B.; Fujimoto, M.; Tedder, T. F. CD22 regulates B lymphocyte function in vivo through both ligand-dependent and ligand-independent mechanisms. Nat. Immunol. 2004, 5, 1078-1087.
45. Jellusova, J.; Nitschke, L. Regulation of B cell functions by the sialic acid-binding receptors siglec-G and CD22. Front. Immunol. 2011, 2, 96.
46. Dörner, T.; Shock, A.; Goldenberg, D. M.; Lipsky, P. E. The mechanistic impact of CD22 engagement with epratuzumab on B cell function: Implications for the treatment of systemic lupus erythematosus. Autoimmun. Rev. 2015, 14, 1079-1086.
47. Tamir, I.; Dal Porto, J. M.; Cambier, J. C. Cytoplasmic protein tyrosine phosphatases SHP-1 and SHP-2: regulators of B cell signal transduction. Curr. Opin. Immunol. 2000, 12, 307-315.
48. Powell, L. D.; Jain, R. K.; Matta, K. L.; Sabesan, S.; Varki, A. Characterization of sialyloligosaccharide binding by recombinant soluble and native cell-associated CD22. Evidence for a minimal structural recognition motif and the potential importance of multisite binding. J. Biol. Chem. 1995, 270, 7523-7532.
49. Collins, B. E.; Blixt, O.; Han, S.; Duong, B.; Li, H.; Nathan, J. K.; Bovin, N.; Paulson, J. C. High-affinity ligand probes of CD22 overcome the threshold set by cis ligands to allow for binding, endocytosis, and killing of B cells. J Immunol. 2006, 177, 2994-3003.
50. Peng, W.; Paulson, J. C. CD22 ligands on a natural N-glycan scaffold efficiently deliver toxins to B-lymphoma cells. J. Am. Chem. Soc. 2017, 139, 12450-12458.
51. O’Reilly, M. K.; Collins, B. E.; Han, S.; Liao, L.; Rillahan, C.; Kitov, P. I.; Bundle, D. R.; Paulson, J. C. Bifunctional CD22 ligands use multimeric immunoglobulins as protein scaffolds in assembly of immune complexes on B cells. J. Am. Chem. Soc. 2008, 130, 7736-7745.
52. McEnaney, P. J.; Parker, C. G.; Zhang, A. X.; Spiegel, D. A. Antibody-recruiting molecules: An emerging paradigm for engaging immune function in treating human disease. ACS Chem. Biol. 2012, 7, 1139-1151.
53. Jandus, C.; Boligan, K. F.; Chijioke, O.; Liu, H.; Dahlhaus, M.; Démoulins, T.; Schneider, C.; Wehrli, M.; Hunger, R. E.; Baerlocher, G. M.; Simon, H.-U.; Romero, P.; Münz, C.; von Gunten, S. Interactions between Siglec-7/9 receptors and ligands influence NK cell–dependent tumor immunosurveillance. J. Clin. Invest. 2014, 124, 1810-1820.
54. Hudak, J. E.; Canham, S. M.; Bertozzi, C. R. Glycocalyx engineering reveals a Siglec-based mechanism for NK cell immunoevasion. Nat. Chem. Biol. 2014, 10, 69-75.
55. Nicoll, G.; Avril, T.; Lock, K.; Furukawa, K.; Bovin, N.; Crocker, P. R. Ganglioside GD3 expression on target cells can modulate NK cell cytotoxicity via siglec-7-dependent and -independent mechanisms. Eur. J. Immunol. 2003, 33, 1642-1648.
56. Ito, A.; Handa, K.; Withers, D. A.; Satoh, M.; Hakomori, S. Binding specificity of siglec7 to disialogangliosides of renal cell carcinoma: possible role of disialogangliosides in tumor progression. FEBS Lett. 2001, 504, 82-86.
57. Kawasaki, Y.; Ito, A.; Withers, D. A.; Taima, T.; Kakoi, N.; Saito, S.; Arai, Y. Ganglioside DSGb5, preferred ligand for Siglec-7, inhibits NK cell cytotoxicity against renal cell carcinoma cells. Glycobiology 2010, 20, 1373-1379.
58. Yamaji, T.; Teranishi, T.; Alphey, M. S.; Crocker, P. R.; Hashimoto, Y. A small region of the natural killer cell receptor, Siglec-7, is responsible for its preferred binding to alpha 2,8-disialyl and branched alpha 2,6-sialyl residues. A comparison with Siglec-9. J. Biol. Chem. 2002, 277, 6324-6332.
59. Jäger, S.; Cimermancic, P.; Gulbahce, N.; Johnson, J. R.; McGovern, K. E.; Clarke, S. C.; Shales, M.; Mercenne, G.; Pache, L.; Li, K.; Hernandez, H.; Jang, G. M.; Roth, S. L.; Akiva, E.; Marlett, J.; Stephens, M.; D’Orso, I.; Fernandes, J.; Fahey, M.; Mahon, C.; O’Donoghue, A. J.; Todorovic, A.; Morris, J. H.; Maltby, D. A.; Alber, T.; Cagney, G.; Bushman, F. D.; Young, J. A.; Chanda, S. K.; Sundquist, W. I.; Kortemme, T.; Hernandez, R. D.; Craik, C. S.; Burlingame, A.; Sali, A.; Frankel, A. D.; Krogan, N. J. Global landscape of HIV-human protein complexes. Nature 2011, 481, 365-370.
60. Jain, A.; Liu, R.; Ramani, B.; Arauz, E.; Ishitsuka, Y.; Ragunathan, K.; Park, J.; Chen, J.; Xiang, Y. K.; Ha, T. Probing cellular protein complexes using single-molecule pull-down. Nature 2011, 473, 484-488.
61. Aoki, S. K.; Diner, E. J.; de Roodenbeke, C. t. K.; Burgess, B. R.; Poole, S. J.; Braaten, B. A.; Jones, A. M.; Webb, J. S.; Hayes, C. S.; Cotter, P. A.; Low, D. A. A widespread family of polymorphic contact-dependent toxin delivery systems in bacteria. Nature 2010, 468, 439-442.
62. Stellberger, T.; Häuser, R.; Baiker, A.; Pothineni, V. R.; Haas, J.; Uetz, P. Improving the yeast two-hybrid system with permutated fusions proteins: the Varicella Zoster Virus interactome. Proteome Sci. 2010, 8, 8.
63. Petschnigg, J.; Groisman, B.; Kotlyar, M.; Taipale, M.; Zheng, Y.; Kurat, C. F.; Sayad, A.; Sierra, J. R.; Usaj, M. M.; Snider, J.; Nachman, A.; Krykbaeva, I.; Tsao, M.-S.; Moffat, J.; Pawson, T.; Lindquist, S.; Jurisica, I.; Stagljar, I. The mammalian-membrane two-hybrid assay (MaMTH) for probing membrane-protein interactions in human cells. Nat. Methods 2014, 11, 585-592.
64. Jones, R. B.; Gordus, A.; Krall, J. A.; MacBeath, G. A quantitative protein interaction network for the ErbB receptors using protein microarrays. Nature 2006, 439, 168-174.
65. Liu, B.; Archer, C. T.; Burdine, L.; Gillette, T. G.; Kodadek, T. Label transfer chemistry for the characterization of protein-protein interactions. J. Am. Chem. Soc. 2007, 129, 12348-12349.
66. Li, X. W.; Rees, J. S.; Xue, P.; Zhang, H.; Hamaia, S. W.; Sanderson, B.; Funk, P. E.; Farndale, R. W.; Lilley, K. S.; Perrett, S.; Jackson, A. P. New insights into the DT40 B cell receptor cluster using a proteomic proximity labeling assay. J. Biol. Chem. 2014, 289, 14434-14447.
67. Bar, D. Z.; Atkatsh, K.; Tavarez, U.; Erdos, M. R.; Gruenbaum, Y.; Collins, F. S. Biotinylation by antibody recognition-a method for proximity labeling. Nat. Methods 2018, 15, 127-133.
68. Leitner, A.; Walzthoeni, T.; Aebersold, R. Lysine-specific chemical cross-linking of protein complexes and identification of cross-linking sites using LC-MS/MS and the xQuest/xProphet software pipeline. Nat. Protoc. 2013, 9, 120-137.
69. Kim, D. I.; Roux, K. J. Filling the void: Proximity-based labeling of proteins in living cells. Trends Cell Biol. 2016, 26, 804-817.
70. Rees, J. S.; Li, X.-W.; Perrett, S.; Lilley, K. S.; Jackson, A. P. Protein neighbors and proximity proteomics. Mol. Cell. Proteomics 2015, 14, 2848-2856.
71. Branon, T. C.; Bosch, J. A.; Sanchez, A. D.; Udeshi, N. D.; Svinkina, T.; Carr, S. A.; Feldman, J. L.; Perrimon, N.; Ting, A. Y. Efficient proximity labeling in living cells and organisms with TurboID. Nat. Biotechnol. 2018, 36, 880-887.
72. Lam, S. S.; Martell, J. D.; Kamer, K. J.; Deerinck, T. J.; Ellisman, M. H.; Mootha, V. K.; Ting, A. Y. Directed evolution of APEX2 for electron microscopy and proximity labeling. Nat. Methods 2014, 12, 51-54.
73. Rhee, H. W.; Zou, P.; Udeshi, N. D.; Martell, J. D.; Mootha, V. K.; Carr, S. A.; Ting, A. Y. Proteomic mapping of mitochondria in living cells via spatially restricted enzymatic tagging. Science 2013, 339, 1328-1331.
74. Chen, A. L.; Kim, E. W.; Toh, J. Y.; Vashisht, A. A.; Rashoff, A. Q.; Van, C.; Huang, A. S.; Moon, A. S.; Bell, H. N.; Bentolila, L. A.; Wohlschlegel, J. A.; Bradley, P. J. Novel components of the Toxoplasma inner membrane complex revealed by BioID. mBio 2015, 6, e02357−14.
75. Krishnamurthy, A.; Jimeno, A. Bispecific antibodies for cancer therapy: A review. Pharmacol. Ther. 2018, 185, 122-134.
76. Sawa, M.; Hsu, T.-L.; Itoh, T.; Sugiyama, M.; Hanson, S. R.; Vogt, P. K.; Wong, C.-H. Glycoproteomic probes for fluorescent imaging of fucosylated glycans in vivo. Proc. Natl. Acad. Sci. U.S.A. 2006, 103, 12371-12376.
77. Krall, N.; da Cruz, F. P.; Boutureira, O.; Bernardes, G. J. L. Site-selective protein-modification chemistry for basic biology and drug development. Nat. Chem. 2016, 8, 103-113.
78. Li, X.; Fang, T.; Boons, G.-J. Preparation of well-defined antibody-drug conjugates through glycan remodeling and strain-promoted azide-alkyne cycloadditions. Angew. Chem., Int. Ed. 2014, 53, 7179-7182.
79. Witus, L. S.; Francis, M. B. Using synthetically modified proteins to make new materials. Acc. Chem. Res. 2011, 44, 774-783.
80. Kim, C. H.; Axup, J. Y.; Schultz, P. G. Protein conjugation with genetically encoded unnatural amino acids. Curr. Opin. Chem. Biol. 2013, 17, 412-419.
81. Gong, Y.; Pan, L. Recent advances in bioorthogonal reactions for site-specific protein labeling and engineering. Tetrahedron Lett. 2015, 56, 2123-2132.
82. Baker, A. S.; Deiters, A. Optical control of protein function through unnatural amino acid mutagenesis and other optogenetic approaches. ACS Chem. Biol. 2014, 9, 1398-1407.
83. Gautier, A.; Deiters, A.; Chin, J. W. Light-activated kinases enable temporal dissection of signaling networks in living cells. J. Am. Chem. Soc. 2011, 133, 2124-2127.
84. Lemke, E. A.; Summerer, D.; Geierstanger, B. H.; Brittain, S. M.; Schultz, P. G. Control of protein phosphorylation with a genetically encoded photocaged amino acid. Nat. Chem. Biol. 2007, 3, 769-772.
85. Wu, N.; Deiters, A.; Cropp, T. A.; King, D.; Schultz, P. G. A genetically encoded photocaged amino acid. J. Am. Chem. Soc. 2004, 126, 14306-14307.
86. Deiters, A.; Groff, D.; Ryu, Y.; Xie, J.; Schultz, P. G. A genetically encoded photocaged tyrosine. Angew. Chem., Int. Ed. 2006, 45, 2728-2731.
87. Baslé, E.; Joubert, N.; Pucheault, M. Protein chemical modification on endogenous amino acids. Chem. Biol. 2010, 17, 213-227.
88. Tanaka, K.; Fujii, Y.; Fukase, K. Site-selective and nondestructive protein labeling through azaelectrocyclization-induced cascade reactions. ChemBioChem 2008, 9, 2392-2397.
89. Fuhrmann, J.; Clancy, K. W.; Thompson, P. R. Chemical biology of protein arginine modifications in epigenetic regulation. Chem. Rev. 2015, 115, 5413-5461.
90. Chen, G.; Heim, A.; Riether, D.; Yee, D.; Milgrom, Y.; Gawinowicz, M. A.; Sames, D. Reactivity of functional groups on the protein surface:  development of epoxide probes for protein labeling. J. Am. Chem. Soc. 2003, 125, 8130-8133.
91. Schlick, T. L.; Ding, Z.; Kovacs, E. W.; Francis, M. B. Dual-Surface Modification of the Tobacco Mosaic Virus. J. Am. Chem. Soc. 2005, 127, 3718-3723.
92. McFarland, J. M.; Joshi, N. S.; Francis, M. B. Characterization of a three-component coupling reaction on proteins by isotopic labeling and nuclear magnetic resonance spectroscopy. J. Am. Chem. Soc. 2008, 130, 7639-7644.
93. Rosen, C. B.; Francis, M. B. Targeting the N terminus for site-selective protein modification. Nat. Chem. Biol. 2017, 13, 697-705.
94. Koshi, Y.; Nakata, E.; Miyagawa, M.; Tsukiji, S.; Ogawa, T.; Hamachi, I. Target-specific chemical acylation of lectins by ligand-tethered DMAP catalysts. J. Am. Chem. Soc. 2008, 130, 245-251.
95. Song, Z.; Takaoka, Y.; Kioi, Y.; Komatsu, K.; Tamura, T.; Miki, T.; Hamachi, I. Extended affinity-guided DMAP chemistry with a finely tuned acyl donor for intracellular FKBP12 labeling. Chem. Lett. 2014, 44, 333-335.
96. Tamura, T.; Song, Z.; Amaike, K.; Lee, S.; Yin, S.; Kiyonaka, S.; Hamachi, I. Affinity-guided oxime chemistry for selective protein acylation in live tissue systems. J. Am. Chem. Soc. 2017, 139, 14181-14191.
97. Heidler, P.; Link, A. N-acyl-N-alkyl-sulfonamide anchors derived from Kenner's safety-catch linker: powerful tools in bioorganic and medicinal chemistry. Bioorg. Med. Chem. 2005, 13, 585-599.
98. Falchi, A.; Giacomelli, G.; Porcheddu, A.; Taddei, M. 4-(4,6-dimethoxy[1,3,5]triazin-2-yl)-4-methyl-morpholinium chloride (DMTMM): A valuable alternative to PyBOP for solid phase peptide synthesis. Synlett 2000, 275–277.
99. D’Este, M.; Eglin, D.; Alini, M. A systematic analysis of DMTMM vs EDC/NHS for ligation of amines to hyaluronan in water. Carbohydr. Polym. 2014, 108, 239-246.
100. Tsukiji, S.; Miyagawa, M.; Takaoka, Y.; Tamura, T.; Hamachi, I. Ligand-directed tosyl chemistry for protein labeling in vivo. Nat. Chem. Biol. 2009, 5, 341-343.
101. Tamura, T.; Tsukiji, S.; Hamachi, I. Native FKBP12 engineering by ligand-directed tosyl chemistry: labeling properties and application to photo-cross-linking of protein complexes in vitro and in living cells. J. Am. Chem. Soc. 2012, 134, 2216-2226.
102. Fujishima, S.-h.; Yasui, R.; Miki, T.; Ojida, A.; Hamachi, I. Ligand-directed acyl imidazole chemistry for labeling of membrane-bound proteins on live cells. J. Am. Chem. Soc. 2012, 134, 3961-3964.
103. Vodovozova, E. L. Photoaffinity labeling and its application in structural biology. Biochemistry (Moscow) 2007, 72, 1-20.
104. Herner, A.; Marjanovic, J.; Lewandowski, T. M.; Marin, V.; Patterson, M.; Miesbauer, L.; Ready, D.; Williams, J.; Vasudevan, A.; Lin, Q. 2-Aryl-5-carboxytetrazole as a new photoaffinity label for drug target identification. J. Am. Chem. Soc. 2016, 138, 14609-14615.
105. Singh, A.; Thornton, E. R.; Westheimer, F. H. The photolysis of diazoacetylchymotrypsin. J. Biol. Chem. 1962, 237, PC3006-3008.
106. Meier, H.; Zeller, K.-P. The Wolff rearrangement of α‐diazo carbonyl compounds. Angew. Chem., Int. Ed. 1975, 14, 32-43.
107. Smith, R. A. G.; Knowles, J. R. The preparation and photolysis of 3-aryl-3H-diazirines. J. Chem. Soc., Perkin Trans. 2, 1975, 686-694
108. Church, R. F. R.; Weiss, M. J. Diazirines. II. Synthesis and properties of small functionalized diazirine molecules. Observations on the reaction of a diaziridine with the iodine-iodide ion system. J. Org. Chem. 1970, 35, 2465-2471.
109. Brunner, J.; Senn, H.; Richards, F. M. 3-Trifluoromethyl-3-phenyldiazirine. A new carbene generating group for photolabeling reagents. J. Biol. Chem. 1980, 255, 3313-3318.
110. Leriche, G.; Chisholm, L.; Wagner, A. Cleavable linkers in chemical biology. Bioorg. Med. Chem. 2012, 20, 571-582.
111. Zhang, X.; Malhotra, S.; Molina, M.; Haag, R. Micro- and nanogels with labile crosslinks - from synthesis to biomedical applications. Chem. Soc. Rev. 2015, 44, 1948-1973.
112. Mortensen, M. R.; Skovsgaard, M. B.; Okholm, A. H.; Scavenius, C.; Dupont, D. M.; Rosen, C. B.; Enghild, J. J.; Kjems, J.; Gothelf, K. V. Small-molecule probes for affinity-guided introduction of biocompatible handles on metal-binding proteins. Bioconjugate Chem. 2018, 29, 3016-3025.
113. Pillow, T. H.; Sadowsky, J. D.; Zhang, D.; Yu, S. F.; Del Rosario, G.; Xu, K.; He, J.; Bhakta, S.; Ohri, R.; Kozak, K. R.; Ha, E.; Junutula, J. R.; Flygare, J. A. Decoupling stability and release in disulfide bonds with antibody-small molecule conjugates. Chem. Sci. 2017, 8, 366-370.
114. Hamann, P. R.; Hinman, L. M.; Beyer, C. F.; Lindh, D.; Upeslacis, J.; Flowers, D. A.; Bernstein, I. An anti-CD33 antibody-calicheamicin conjugate for treatment of acute myeloid leukemia. Choice of linker. Bioconjugate Chem. 2002, 13, 40-46.
115. Schneider, E. M.; Zeltner, M.; Zlateski, V.; Grass, R. N.; Stark, W. J. Click and release: fluoride cleavable linker for mild bioorthogonal separation. Chem. Commun. 2016, 52, 938-941.
116. Tomohiro, T.; Kato, K.; Masuda, S.; Kishi, H.; Hatanaka, Y. Photochemical construction of coumarin fluorophore on affinity-anchored protein. Bioconjugate Chem. 2011, 22, 315-318.
117. Tomohiro, T.; Inoguchi, H.; Masuda, S.; Hatanaka, Y. Affinity-based fluorogenic labeling of ATP-binding proteins with sequential photoactivatable cross-linkers. Bioorg. Med. Chem. Lett. 2013, 23, 5605-5608.
118. Morimoto, S.; Tomohiro, T.; Maruyama, N.; Hatanaka, Y. Photoaffinity casting of a coumarin flag for rapid identification of ligand-binding sites within protein. Chem. Commun. 2013, 49, 1811-1813.
119. Klymchenko, A. S. Solvatochromic and fluorogenic dyes as environment-sensitive probes: design and biological applications. Acc. Chem. Res. 2017, 50, 366-375.
120. Khan, S.; Gupta, A.; Verma, N. C.; Nandi, C. K. Time-resolved emission reveals ensemble of emissive states as the origin of multicolor fluorescence in carbon dots. Nano Lett. 2015, 15, 8300-8305.
121. Lakowicz, J. R. Principles of Fluorescence Spectroscopy, 3rd ed.; Springer: New York, 2006.
122. Olsson, T. S. G.; Williams, M. A.; Pitt, W. R.; Ladbury, J. E. The thermodynamics of protein-ligand interaction and solvation: insights for ligand design. J. Mol. Biol. 2008, 384, 1002-1017.
123. Myslinski, J. M.; DeLorbe, J. E.; Clements, J. H.; Martin, S. F. Protein–ligand interactions: Thermodynamic effects associated with increasing nonpolar surface area. J. Am. Chem. Soc. 2011, 133, 18518-18521.
124. MacNevin, C. J.; Gremyachinskiy, D.; Hsu, C.-W.; Li, L.; Rougie, M.; Davis, T. T.; Hahn, K. M. Environment-sensing merocyanine dyes for live cell imaging applications. Bioconjugate Chem. 2013, 24, 215-223.
125. Chen, H.-J.; Chew, C. Y.; Chang, E.-H.; Tu, Y.-W.; Wei, L.-Y.; Wu, B.-H.; Chen, C.-H.; Yang, Y.-T.; Huang, S.-C.; Chen, J.-K.; Chen, I. C.; Tan, K.-T. S-cis diene conformation: A new bathochromic shift strategy for near-infrared fluorescence switchable dye and the imaging applications. J. Am. Chem. Soc. 2018, 140, 5224-5234.
126. Karpenko, I. A.; Collot, M.; Richert, L.; Valencia, C.; Villa, P.; Mély, Y.; Hibert, M.; Bonnet, D.; Klymchenko, A. S. Fluorogenic squaraine dimers with polarity-sensitive folding as bright far-red probes for background-free bioimaging. J. Am. Chem. Soc. 2015, 137, 405-412.
127. Lang, K.; Chin, J. W. Bioorthogonal reactions for labeling proteins. ACS Chem. Biol. 2014, 9, 16-20.
128. Pham, N. D.; Parker, R. B.; Kohler, J. J. Photocrosslinking approaches to interactome mapping. Curr. Opin. Chem. Biol. 2013, 17, 90-101.
129. Carlsen, P. H. J.; Katsuki, T.; Martin, V. S.; Sharpless, K. B. A greatly improved procedure for ruthenium tetroxide catalyzed oxidations of organic compounds. J. Org. Chem. 1981, 46, 3936-3938.
130. Stolowitz, M. L.; Ahlem, C.; Hughes, K. A.; Kaiser, R. J.; Kesicki, E. A.; Li, G.; Lund, K. P.; Torkelson, S. M.; Wiley, J. P. Phenylboronic acid-salicylhydroxamic acid bioconjugates. 1. A novel boronic acid complex for protein immobilization. Bioconjugate Chem. 2001, 12, 229-239.
131. Kikuchi, D.; Sakaguchi, S.; Ishii, Y. An alternative method for the selective bromination of alkylbenzenes using NaBrO3/NaHSO3 reagent. J. Org. Chem. 1998, 63, 6023-6026.
132. Sá, M. M.; Ramos, M. D.; Fernandes, L. Fast and efficient preparation of Baylis–Hillman-derived (E)-allylic azides and related compounds in aqueous medium. Tetrahedron 2006, 62, 11652-11656.
133. Gritter, R. J.; Dupre, G. D.; Wallace, T. J. Oxidation of benzyl alcohols with manganese dioxide. Nature 1964, 202, 179-181.
134. Kambe, T.; Correia, B. E.; Niphakis, M. J.; Cravatt, B. F. Mapping the protein interaction landscape for fully functionalized small-molecule probes in human cells. J. Am. Chem. Soc. 2014, 136, 10777-10782.
135. Montalbetti, C. A. G. N.; Falque, V. Amide Bond Formation and Peptide Coupling. Tetrahedron, 2005, 61, 10827–10852.
136. Morley, T. J.; Withers, S. G. Chemoenzymatic synthesis and enzymatic analysis of 8-modified cytidine monophosphate-sialic acid and sialyl lactose derivatives. J. Am. Chem. Soc. 2010, 132, 9430-9437.
137. Kajihara, Y.; Yamamoto, T.; Nagae, H.; Nakashizuka, M.; Sakakibara, T.; Terada, I. A novel α-2,6-sialyltransferase: Transfer of sialic acid to fucosyl and sialyl trisaccharides. J. Org. Chem. 1996, 61, 8632-8635.
138. Yamamoto, T.; Nakashizuka, M.; Terada, I. Cloning and expression of a marine bacterial beta-galactoside α2,6-sialyltransferase gene from Photobacterium damsela JT0160. J. Biochem. 1998, 123, 94-100.
139. Cheng, J.; Huang, S.; Yu, H.; Li, Y.; Lau, K.; Chen, X. Trans-sialidase activity of Photobacterium damsela α2,6-sialyltransferase and its application in the synthesis of sialosides. Glycobiology 2010, 20, 260-268.
140. Liang, L.; Astruc, D. The copper(I)-catalyzed alkyne-azide cycloaddition (CuAAC) “click” reaction and its applications. An overview. Coord. Chem. Rev. 2011, 255, 2933-2945.
141. Nicolson, G. L.; Blaustein, J.; Etzler, M. E. Characterization of two plant lectins from Ricinus communis and their quantitative interaction with a murine lymphoma. Biochemistry 1974, 13, 196-204.
142. Harvey, D. J.; Wing, D. R.; Kuster, B.; Wilson, I. B. Composition of N-linked carbohydrates from ovalbumin and co-purified glycoproteins. J. Am. Soc. Mass. Spectrom. 2000, 11, 564-571.
143. Gestwicki, J. E.; Cairo, C. W.; Strong, L. E.; Oetjen, K. A.; Kiessling, L. L. Influencing receptor-ligand binding mechanisms with multivalent ligand architecture. J. Am. Chem. Soc. 2002, 124, 14922-14933.
144. Arndt, N. X.; Tiralongo, J.; Madge, P. D.; von Itzstein, M.; Day, C. J. Differential carbohydrate binding and cell surface glycosylation of human cancer cell lines. J. Cell. Biochem. 2011, 112, 2230-2240.
145. Tao, S. C.; Li, Y.; Zhou, J.; Qian, J.; Schnaar, R. L.; Zhang, Y.; Goldstein, I. J.; Zhu, H.; Schneck, J. P. Lectin microarrays identify cell-specific and functionally significant cell surface glycan markers. Glycobiology 2008, 18, 761-769.
146. Ellis, G. A.; Palte, M. J.; Raines, R. T. Boronate-mediated biologic delivery. J. Am. Chem. Soc. 2012, 134, 3631-3634.
147. Sun, T.; Yu, S.-H.; Zhao, P.; Meng, L.; Moremen, K. W.; Wells, L.; Steet, R.; Boons, G.-J. One-step selective exoenzymatic labeling (SEEL) strategy for the biotinylation and identification of glycoproteins of living cells. J. Am. Chem. Soc. 2016, 138, 11575-11582.
148. Wu, Z. L.; Huang, X.; Burton, A. J.; Swift, K. A. D. Probing sialoglycans on fetal bovine fetuin with azido-sugars using glycosyltransferases. Glycobiology 2016, 26, 329-334.
149. Palmisano, G.; Larsen, M. R.; Packer, N. H.; Thaysen-Andersen, M. Structural analysis of glycoprotein sialylation – part II: LC-MS based detection. RSC Adv. 2013, 3, 22706-22726.
150. Junutula, J. R.; Raab, H.; Clark, S.; Bhakta, S.; Leipold, D. D.; Weir, S.; Chen, Y.; Simpson, M.; Tsai, S. P.; Dennis, M. S.; Lu, Y.; Meng, Y. G.; Ng, C.; Yang, J.; Lee, C. C.; Duenas, E.; Gorrell, J.; Katta, V.; Kim, A.; McDorman, K.; Flagella, K.; Venook, R.; Ross, S.; Spencer, S. D.; Lee Wong, W.; Lowman, H. B.; Vandlen, R.; Sliwkowski, M. X.; Scheller, R. H.; Polakis, P.; Mallet, W. Site-specific conjugation of a cytotoxic drug to an antibody improves the therapeutic index. Nat. Biotechnol. 2008, 26, 925-932.
151. Alley, S. C.; Okeley, N. M.; Senter, P. D. Antibody-drug conjugates: targeted drug delivery for cancer. Curr. Opin. Chem. Biol. 2010, 14, 529-537.
152. Bartoli, G.; Bosco, M.; Carlone, A.; Dalpozzo, R.; Marcantoni, E.; Melchiorre, P.; Sambri, L. Reaction of dicarbonates with carboxylic acids catalyzed by weak Lewis acids: general method for the synthesis of anhydrides and esters. Synthesis 2007, 22, 3489-3496.
153. Gilbert, M.; Brisson, J. R.; Karwaski, M. F.; Michniewicz, J.; Cunningham, A. M.; Wu, Y.; Young, N. M.; Wakarchuk, W. W. Biosynthesis of ganglioside mimics in Campylobacter jejuni OH4384. Identification of the glycosyltransferase genes, enzymatic synthesis of model compounds, and characterization of nanomole amounts by 600-MHz (1)H and (13)C NMR analysis. J. Biol. Chem. 2000, 275, 3896-3906.
154. Gilbert, M.; Karwaski, M. F.; Bernatchez, S.; Young, N. M.; Taboada, E.; Michniewicz, J.; Cunningham, A. M.; Wakarchuk, W. W. The genetic bases for the variation in the lipo-oligosaccharide of the mucosal pathogen, Campylobacter jejuni. Biosynthesis of sialylated ganglioside mimics in the core oligosaccharide. J. Biol. Chem. 2002, 277, 327-337.
155. Liang, J.; Zhang, Z.; Zhao, H.; Wan, S.; Zhai, X.; Zhou, J.; Liang, R.; Deng, Q.; Wu, Y.; Lin, G. Simple and rapid monitoring of doxorubicin using streptavidin-modified microparticle-based time-resolved fluorescence immunoassay. RSC Adv. 2018, 8, 15621-15631.
156. Hou, H.; Zhao, Y.; Li, C.; Wang, M.; Xu, X.; Jin, Y. Single-cell pH imaging and detection for pH profiling and label-free rapid identification of cancer-cells. Sci. Rep. 2017, 7, 1759.
157. Park, J. W.; Hong, K.; Kirpotin, D. B.; Colbern, G.; Shalaby, R.; Baselga, J.; Shao, Y.; Nielsen, U. B.; Marks, J. D.; Moore, D.; Papahadjopoulos, D.; Benz, C. C. Anti-HER2 immunoliposomes: Enhanced efficacy attributable to targeted delivery. Clin. Cancer Res. 2002, 8, 1172-1181.
158. Hamouda, H.; Kaup, M.; Ullah, M.; Berger, M.; Sandig, V.; Tauber, R.; Blanchard, V. Rapid analysis of cell surface N-glycosylation from living cells using mass spectrometry. J. Proteome Res. 2014, 13, 6144-6151.
159. Goh, J. B.; Ng, S. K. Impact of host cell line choice on glycan profile. Crit. Rev. Biotechnol. 2018, 38, 851-867.
160. Chen, J.; Stubbe, J. Bleomycins: Towards better therapeutics. Nat. Rev. Cancer 2005, 5, 102-112.
161. Chapuis, J. C.; Schmaltz, R. M.; Tsosie, K. S.; Belohlavek, M.; Hecht, S. M. Carbohydrate dependent targeting of cancer cells by bleomycin-microbubble conjugates. J. Am. Chem. Soc. 2009, 131, 2438-2439.
162. Yu, Z.; Schmaltz, R. M.; Bozeman, T. C.; Paul, R.; Rishel, M. J.; Tsosie, K. S.; Hecht, S. M. Selective tumor cell targeting by the disaccharide moiety of bleomycin. J. Am. Chem. Soc. 2013, 135, 2883-2886.
163. Bhattacharya, C.; Yu, Z.; Rishel, M. J.; Hecht, S. M. The carbamoylmannose moiety of bleomycin mediates selective tumor cell targeting. Biochemistry 2014, 53, 3264-3266.
164. Punnonen, E. L.; Ryhanen, K.; Marjomaki, V. S. At reduced temperature, endocytic membrane traffic is blocked in multivesicular carrier endosomes in rat cardiac myocytes. Eur. J. Cell Biol. 1998, 75, 344-352.
165. Yamano, S.; Dai, J.; Yuvienco, C.; Khapli, S.; Moursi, A. M.; Montclare, J. K. Modified Tat peptide with cationic lipids enhances gene transfection efficiency via temperature-dependent and caveolae-mediated endocytosis. J. Controlled Release 2011, 152, 278-285.
166. Liu, R.; Li, H.; Gao, X.; Mi, Q.; Zhao, H.; Gao, Q. Mannose-conjugated platinum complexes reveals effective tumor targeting mediated by glucose transporter 1. Biochem. Biophys. Res. Commun. 2017, 487, 34-40.
167. Augustin, R. The protein family of glucose transport facilitators: It's not only about glucose after all. IUBMB Life 2010, 62, 315-333.
168. Krzeslak, A.; Wojcik-Krowiranda, K.; Forma, E.; Jozwiak, P.; Romanowicz, H.; Bienkiewicz, A.; Brys, M. Expression of GLUT1 and GLUT3 glucose transporters in endometrial and breast cancers. Pathol. Oncol. Res. 2012, 18, 721-728.
169. Heuser, J. E.; Anderson, R. G. Hypertonic media inhibit receptor-mediated endocytosis by blocking clathrin-coated pit formation. J. Cell Biol. 1989, 108, 389-400.