分子間相互作用解析 ITC的最新趨勢
MicroCal產品的應用經理Verna Frasca使用Google學術搜尋，調查截至2018年6月30日與ITC相關的論文。報告如下。
何謂ITC 〜分子間相互作用解析的黃金標準〜
ITC被譽為蛋白質、核酸、脂質等生物大分子的分子間相互作用解析的黃金標準。其特點不僅在於能求出結合的強度，還能獲得化學計量及熱力學參數。
ITC的歷史 〜世界上首台ITC是MicroCal〜
時光倒流至1987年。在美國東海岸的北安普敦的MicroCal LLC（現為Malvern Panalytical）從一個名為OMEGA的系統開始銷售。（驚人的是，至今仍有OMEGA在運行！）隨後，1992年推出MCS ITC，1998年推出VP-ITC（至今仍然銷售中！），2007年推出成功縮小容量的iTC200。2004年開發出世界第一台全自動的AutoITC，2008年推出顯著改進版本Auto-iTC200。2015年，進行了硬體及軟體的升級，開始製造、銷售PEAQ-ITC和PEAQ-ITC Automated。
世界各地有數千台ITC被用於生命科學領域的研究機構，以及小分子與生物製藥製造商中。
ITC論文調查 〜ITC使用的論文數量大幅增加〜
使用Google學術搜尋，每5年期間用「MicroCal +（列舉ITC的產品名以“or”連接）」進行搜尋，得到以下結果。
- 1988-1992: 15 次命中
- 1993-1997: 246 次命中
- 1998-2002: 857 次命中
- 2003-2007: 2250 次命中
- 2008-2012: 4360 次命中
- 2013-2018: 5800 次命中
MicroCal ITC使用的論文數量顯著上升。
詳細瀏覽這些論文，可以看到測量了各種分子間相互作用類型。例如，蛋白質-小分子、蛋白質-蛋白質、蛋白質-DNA、抗原-抗體，以及酶和底物等。ITC通常用於評估作為低分子藥物候選物質的化合物和其目標分子（主要是蛋白質）的結合。此外，納米顆粒、聚合物、膜、表面活性劑及膠束等領域的評估也在增加。
這些研究被發表在超過350本出版物，其中自2015年1月到2018年6月底，至少有25篇論據使用了MicroCal ITC的系統，以下為32本這類出版物。（論據數量為四捨五入）
雜誌發表的ITC測量案例
以下介紹了發表於各種雜誌上的ITC測量案例。（全部為英文）
Acta parasitological: “Measurement of binding strength between prey proteins interacting with Toxoplasma gondii SAG1 and SAG2 using isothermal titration calorimetry (ITC)”
AIDS: “Design of a highly potent HIV-1 fusion inhibitor targeting the gp41 pocket”
Allergy: “Characterization of maize chitinase‐A, a tough allergenic molecule”
Anesthesiology: “Discovery of a novel general anesthetic chemotype using high-throughput screening”
Archives of Toxicology: “Interaction of perfluoroalkyl acids with human liver fatty acid-binding protein”
Bioengineering & Translational Medicine: “Targeting HPV‐infected cervical cancer cells with PEGylated liposomes encapsulating siRNA and the role of siRNA complexation with polyethylenimine”
Biomedicine & Pharmacotherapy: “Nanobodies targeting cortactin proline rich, helical and actin binding regions downregulate invadopodium formation and matrix degradation in SCC-61 cancer cells”
Blood: “Structural basis for quinine-dependent antibody binding to platelet integrin αIIbβ3”
Breast Cancer Research: “Gossypol has anti-cancer effects by dual-targeting MDM2 and VEGF in human breast cancer”
Cell Host & Microbe: “Structural conservation despite huge sequence diversity allows EPCR binding by the PfEMP1 family implicated in severe childhood malaria”
Cerebral Cortex: “Cortical layer inversion and deregulation of reelin signaling in the absence of SOCS6 and SOCS7”
Chemical Research in Toxicology: “Identification and Molecular Interaction Studies of Thyroid Hormone Receptor Disruptors among Household Dust Contaminants”
Chemistry Select: “An ITC Study on the Interaction Energy Between Galactomannan Biopolymers and Selected MO2 Nanoparticles in Hydrogels”
ChemNanoMat: “The Effect of PEGylation on Multivalent Binding: A Surface Plasmon Resonance and Isothermal Titration Calorimetry Study with Structurally Diverse PEG‐Dendritic GATG Copolymers”
Chirality: “Isothermal Titration Calorimetry of Chiral Polymeric Nanoparticles”
Clinical and Translational Oncology: “Selection of DNA aptamers for extra cellular domain of human epidermal growth factor receptor 2 to detect HER2 positive carcinomas”
Cogent Biology: “Isolation and purification of phytocystatin from almond: Biochemical, biophysical, and immunological characterization”
Colloid and Polymer Science: “Adsorption of lysozyme on pH-responsive PnBA-b-PAA polymeric nanoparticles: studies by stopped-flow SAXS and ITC”
Extremophiles: “High-affinity RNA binding by a hyperthermophilic single-stranded DNA-binding protein”
Flavour and Fragrance Journal: “Facile separation of cinnamyl acetate and cinnamaldehyde based on host–guest complexation with β‐cyclodextrin”
Food Chemistry: “Effect of the addition of mannoproteins on the interaction between wine flavonols and salivary proteins”
Food Research International: “Evaluation of butyrylcholinesterase inhibitory activity by chlorogenic acids and coffee extracts assessed in ITC and docking simulation models”
Journal of Agricultural and Food Chemistry: “Ethanol Concentration Influences the Mechanisms of Wine Tannin Interactions with Poly(l-proline) in Model Wine”
Water, Air, & Soil Pollution: “Exploring the Effect of Cu2+ on Sludge Hydrolysis and Interaction Mechanism between Cu2+ and Xylanase by Multispectral and Thermodynamic Methods”
2015年以後出版的以下出版物中包含有使用MicroCal ITC的程序章節。
AMPK (Methods in Molecular Biology, volume 1732): “Applications of NMR and ITC for the Study of the Kinetics of Carbohydrate Binding by AMPK β-Subunit Carbohydrate-Binding Modules”
Antimicrobial Peptides (Methods in Molecular Biology, volume 1548): “Calorimetry Methods to Study Membrane Interactions and Perturbations Induced by Antimicrobial Host Defense Peptides”
Applied Biophysics for Drug Discovery: “Thermodynamics in Drug Discovery”
Biocalorimetry (Methods, volume 76):
Biocalorimetry: Foundations and Contemporary Approaches
Biochemical Roles of Eukaryotic Cell Surface Macromolecules (Advances in Experimental Medicine and Biology, volume 842): “Biophysical Characterization of the Interaction of O-acylcholines with the Major Bovine Seminal Plasma Protein, PDC-109”
c-Di-GMP Signaling (Methods in Molecular Biology, volume 1657): “Isothermal Titration Calorimetry to Determine Apparent Dissociation Constants (Kd) and Stoichiometry of Interaction (n) of C-di-GMP Binding Proteins”
Calorimetry (Methods in Enzymology, volume 567)
Current Protocols in Nucleic Acid Chemistry: “Calorimetry of Nucleic Acids”
Excipient Applications in Formulation Design and Drug Delivery: “Drug Excipient interactions”
Glycosaminoglycans: “Using Isothermal Titration Calorimetry to Determine Thermodynamic Parameters of Protein–Glycosaminoglycan Interaction”
In Vitro Mutagenesis (Methods in Molecular Biology, volume 1498): “Biochemical and Biophysical Methods to Examine the Effects of Site-Directed Mutagenesis on Enzymatic Activities and Interprotein Interactions”
Molecular Physiology and Ecophysiology of Sulfur: “Investigation of Protein-Protein Interactions of Ferredoxin and Sulfite Reductase Under Different Sodium Chloride Concentrations by NMR Spectroscopy and Isothermal Titration Calorimetry”
Nucleic Acid Aptamers (Methods in Molecular Biology, volume 1380): “Label-free determination of the dissociation constant of small molecule-aptamer interaction by isothermal titration calorimetry”
Nucleic Acid Crystallography (Methods in Molecular Biology, volume 1320): “Isothermal Titration Calorimetry: Assisted Crystallization of RNA–Ligand Complexes”
Polymer Micelles: “Micellization Thermodynamics of Pluronic P123 (EO20PO70EO20) Amphiphilic Block Copolymer in Aqueous Ethylammonium Nitrate (EAN) Solutions”
Potassium Channels (Methods in Molecular Biology, volume 1684): “Ion Binding to Transport Proteins using Isothermal Titration Calorimetry”
Semaphorin Signaling Methods (Methods in Molecular Biology, volume 1493): “Characterizing Plexin GTPase Interactions Using Gel Filtration, Surface Plasmon Resonance Spectrometry, and Isothermal Titration Calorimetry”
SH2 Domains (Methods in Molecular Biology, volume 1555): “Calorimetric measurement of SH2 domain ligand affinities”
Thermodynamics and Kinetics of Drug Binding: “Thermodynamic Profiling of Carbonic Anhydrase Inhibitors”
Vitamin C: “Encapsulation of Vitamin C into β‐Cyclodextrin for Advanced and Regulatory Release”
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