Study of the binding interaction between fluorinated matrix metalloproteinase inhibitors and Human Serum Albumin.

Published on May 22, 2014in European Journal of Medicinal Chemistry5.572
· DOI :10.1016/J.EJMECH.2014.03.064
Giuseppe Digilio18
Estimated H-index: 18
Tiziano Tuccinardi35
Estimated H-index: 35
(UniPi: University of Pisa)
+ 6 AuthorsArmando Rossello28
Estimated H-index: 28
(UniPi: University of Pisa)
Abstract Fluorinated, arylsulfone-based inhibitors of Matrix Metalloproteinases (MMP) have been used, in the [ 18 F]-radiolabelled version, as radiotracers targeted to MMP-2/9 for Positron Emission Tomography (PET). Although they showed acceptable tumour uptake, specificity was rather low. To get further insights into the reason of low specificity, the binding interaction of these compounds with Human Serum Albumin (HSA) has been investigated. 19 F NMR spectroscopy showed that all compounds considered partition between multiple HSA binding sites, being characterized by either slow-exchange kinetics (with K a in the order of 10 5  M −1 ) and fast-exchange kinetics (with K a in the order of 10 4  M -1 ). For 2-(2-(4′-(2-fluoroethoxy)biphenyl-4-ylsulfonyl)phenyl)acetic acid ( 1a ) and 2-(2-(4′-(2-fluoroacetamido)biphenyl-4-ylsulfonyl)phenyl)acetic acid ( 1c ), these slow and fast-exchanging binding sites could be mapped to Sudlow's site I and II, respectively. It is shown that high affinity albumin binding constitutes a theoretical limitation for the specificity achievable by MMP-inhibitors as MMP-targeted PET tracers in cancer imaging, because albumin accumulating aspecifically in tumours lowers the binding potential of radiotracers.
📖 Papers frequently viewed together
18 Citations
19 Citations
8 Citations
#1Nathalie Matusiak (UMCG: University Medical Center Groningen)H-Index: 3
#2Aren van WaardeH-Index: 34
view all 7 authors...
Dysregulation of matrix metalloproteinase (MMP) activity can lead to a wide range of disease states such as atherosclerosis, inflammation or cancer. The ability to image MMP activity non-invasively in vivo, by radiolabelled synthetic inhibitors, would allow the characterization of atherosclerotic plaques, inflammatory lesions or tumors. Here we present an overview of radiolabelled MMP inhibi- tors (MMPIs) and MMP peptides for positron emission tomography (PET) and single photon emission computed...
48 CitationsSource
#1F Casalini (University of Eastern Piedmont)H-Index: 1
#1Francesca CasaliniH-Index: 10
Last. Alessandro MaiocchiH-Index: 14
view all 20 authors...
New fluorinated, arylsulfone-based matrix metalloproteinase (MMP) inhibitors containing carboxylate as the zinc binding group were synthesized as radiotracers for positron emission tomography. Inhibitors were characterized by Ki for MMP-2 in the nanomolar range and by a fair selectivity for MMP-2/9/12/13 over MMP-1/3/14. Two of these compounds were obtained in the 18F-radiolabeled form, with radiochemical purity and yield suitable for preliminary studies in mice xenografted with a human U-87 MG ...
10 CitationsSource
#1Bianca WaschkauH-Index: 5
#2Andreas Faust (European Institute)H-Index: 20
Last. Christoph Bremer (WWU: University of Münster)H-Index: 28
view all 4 authors...
Matrix metalloproteinases (MMPs) are proteolytic enzymes that degrade structural components of the extracellular matrix and participate in pathologies such as cancer and inflammatory disorders. The development of novel contrast agents for optical imaging of MMP activity in vivo is of great interest. The commonly used near-infrared fluorescence-compatible agents are dye-quenched probes that do not emit fluorescence until they interact with MMPs. In contrast, fluorescent synthetic low-molecular-we...
27 CitationsSource
#1Verena HugenbergH-Index: 6
#2Hans-Jörg BreyholzH-Index: 17
Last. Stefan WagnerH-Index: 19
view all 13 authors...
In vivo imaging of MMPs is of great (pre)clinical interest and can potentially be realized with modern three-dimensional and noninvasive in vivo molecular imaging techniques such as positron emission tomography (PET). Consequently, MMP inhibitors (MMPIs) radiolabeled with positron emitting nuclides (e.g., 18F) represent a suitable tool for the visualization of activated MMPs with PET. On the basis of our previous work and results regarding radiolabeled and unlabeled derivatives of the nonselecti...
39 CitationsSource
#1Concetta V. Gringeri (University of Eastern Piedmont)H-Index: 10
Last. Silvio Aime (UNITO: University of Turin)H-Index: 91
view all 9 authors...
Two novel Gd-based contrast agents (CAs) for the molecular imaging of matrix metalloproteinases (MMPs) were synthetized and characterized in vitro and in vivo. These probes were based on the PLG*LWAR peptide sequence, known to be hydrolyzed between Gly and Leu by a broad panel of MMPs. A Gd–DOTA chelate was conjugated to the N-terminal position through an amide bond, either directly to proline (compd Gd–K11) or through a hydrophilic spacer (compd Gd–K11N). Both CA were made strongly amphiphilic ...
16 CitationsSource
#1João M. C. Teixeira (UC: University of Coimbra)H-Index: 11
#2David M. Dias (UC: University of Coimbra)H-Index: 9
Last. Carlos F. G. C. Geraldes (UC: University of Coimbra)H-Index: 55
view all 7 authors...
The study of ligand–receptor interactions using high-resolution NMR techniques, namely the saturation transfer difference (STD), is presented for the recognition process between La(III) complexes of 1,4,7,10-tetrakis(carboxymethyl)-1,4,7,10-tetraazacyclododecane monoamide and diethylenetriaminepentaacetic acid bisamide glycoconjugates and the galactose-specific lectin Ricinus communis agglutinin (RCA120). This new class of Gd(III)-based potential targeted MRI contrast agents (CAs), bearing one o...
5 CitationsSource
#1Ulrich auf dem Keller (UBC: University of British Columbia)H-Index: 35
#2Caroline L. BellacH-Index: 10
Last. Christopher M. OverallH-Index: 99
view all 14 authors...
Matrix metalloproteinases (MMP), strongly associated pathogenic markers of cancer, have undergone extensive drug development programs. Marimastat, a noncovalent MMP inhibitor, was conjugated with FITC to label cellular metalloproteinase cancer targets in MDA-MB-231 cells in vitro . Punctate localization of active transmembrane MMP14 was observed. For molecular-targeted positron emission tomography imaging of syngeneic 67NR murine mammary carcinoma in vivo , marimastat was 18 F-labeled using a sh...
75 CitationsSource
#1Hans-Jörg Breyholz (WWU: University of Münster)H-Index: 17
#2Stefan Wagner (WWU: University of Münster)H-Index: 19
Last. Klaus Kopka (WWU: University of Münster)H-Index: 56
view all 9 authors...
Matrix metalloproteinases (MMPs) are zinc- and calcium-dependent endopeptidases. Representing a subfamily of the metzincin superfamily, MMPs are involved in the proteolytic degradation of components of the extracellular matrix. Unregulated MMP expression, MMP dysregulation and locally increased MMP activity are common features of various diseases, such as cancer, atherosclerosis, stroke, arthritis, and others. Therefore, activated MMPs are suitable biological targets for the specific visualizati...
53 CitationsSource
#1Emilia S. Olson (UCSD: University of California, San Diego)H-Index: 13
#2Tao Jiang (UCSD: University of California, San Diego)H-Index: 13
Last. Roger Y. Tsien (UCSD: University of California, San Diego)H-Index: 172
view all 7 authors...
High-resolution imaging of molecules intrinsically involved in malignancy and metastasis would be of great value for clinical detection and staging of tumors. We now report in vivo visualization of matrix metalloproteinase activities by MRI and fluorescence of dendrimeric nanoparticles coated with activatable cell penetrating peptides (ACPPs), labeled with Cy5, gadolinium, or both. Uptake of such nanoparticles in tumors is 4- to 15-fold higher than for unconjugated ACPPs. With fluorescent molecu...
461 CitationsSource
#1Javier Cortes (Hebron University)H-Index: 76
#2Cristina Saura (Hebron University)H-Index: 33
Abstract Breast cancer deaths in western countries are falling due to screening and adjuvant therapy, but the treatment of metastatic breast cancer (MBC) has not shown comparable advances. The most active single agents are taxanes, which extend both disease-free and overall survival. However, opportunities remain for improving outcome. Nanoparticle technology is proving a valuable addition to the pharmaceutical armamentarium, particularly in oncology. Its use to bind paclitaxel to human albumin ...
91 CitationsSource
Cited By10
#1Doretta Cuffaro (UniPi: University of Pisa)H-Index: 5
#2Elisa Nuti (UniPi: University of Pisa)H-Index: 25
Last. Armando Rossello (UniPi: University of Pisa)H-Index: 28
view all 4 authors...
Matrix metalloproteinases (MMPs) and A disintegrin and Metalloproteinase (ADAMs) are zinc-dependent endopeptidases belonging to the metzincin superfamily. Upregulation of metzincin activity is a major feature in many serious pathologies such as cancer, inflammations, and infections. In the last decades, many classes of small molecules have been developed directed to inhibit these enzymes. The principal shortcomings that have hindered clinical development of metzincin inhibitors are low selectivi...
#1Di Wu (BTBU: Beijing Technology and Business University)H-Index: 9
#2Sen MeiH-Index: 1
Last. Chengtao Wang (BTBU: Beijing Technology and Business University)H-Index: 1
view all 8 authors...
Abstract Theaflavin (TF), which is the key pigment in black tea, is a health-promoting food component with beneficial effects on humans. However, the interactions by which these effects are transferred and exerted into protein-rich foods are unclear. Here, egg ovalbumin (OVA) was selected as a representative dietary protein to ascertain their binding mechanism. Steady-state, time-resolved fluorescence and isothermal titration calorimetric results showed that TF can interact well with OVA with an...
19 CitationsSource
#1Yanqiu Zuo (Guilin University of Technology)H-Index: 2
#2Yuefan Rui (Guilin University of Technology)H-Index: 2
Last. Zhongsheng Yi (Guilin University of Technology)H-Index: 4
view all 5 authors...
: Three PBDEs (BDE25, BDE47, and BDE154) were selected to investigate the interactions between PBDEs and hen egg white lysozyme (HEWL) by molecular modeling, fluorescence spectroscopy, and FT-IR spectra. The docking results showed that hydrogen bonds were formed between BDE25 and residue TRP63 and between BDE47 and TRP63 with bond lengths of 2.178 A and 2.146 A, respectively. The molecular dynamics simulations indicated that van der Waals forces played a predominant role in the binding of three ...
#1Elisa Nuti (UniPi: University of Pisa)H-Index: 25
#2Doretta Cuffaro (UniPi: University of Pisa)H-Index: 5
Last. Armando Rossello (UniPi: University of Pisa)H-Index: 28
view all 15 authors...
Matrix metalloproteinase-12 (MMP-12) selective inhibitors could play a role in the treatment of lung inflammatory and cardiovascular diseases. In the present study, the previously reported 4-methoxybiphenylsulfonyl hydroxamate and carboxylate based inhibitors (1b and 2b) were modified to enhance their selectivity for MMP-12. In the newly synthesized thioaryl derivatives, the nature of the zinc binding group (ZBG) and the sulfur oxidation state were changed. Biological assays carried out in vitro...
12 CitationsSource
#1Angélique Gajahi Soudahome (University of La Réunion)H-Index: 1
#2Aurélie Catan (University of La Réunion)H-Index: 6
Last. Joël Couprie (University of La Réunion)H-Index: 3
view all 14 authors...
: The long-acting glucagon-like peptide-1 analogue liraglutide has proven efficiency in the management of type 2 diabetes and also has beneficial effects on cardiovascular diseases. Liraglutide's protracted action highly depends on its capacity to bind to albumin via its palmitic acid part. However, in diabetes, albumin can undergo glycation, resulting in impaired drug binding. Our objective in this study was to assess the impact of human serum albumin (HSA) glycation on liraglutide affinity. Us...
7 CitationsSource
#1Di Wu (Sichuan University)H-Index: 36
#1Di Wu (Sichuan University)H-Index: 42
Last. Hui Li (Sichuan University)H-Index: 20
view all 7 authors...
Abstract Monitoring the interaction between drugs and proteins is critical to understanding drug transport and metabolism underlying pharmacodynamics. The binding capacities to human serum albumin of two anticancer drugs, capecitabine and gefitinib, were compared via an approach combining 19 F NMR, 1 H saturation transfer difference (STD) NMR, circular dichroism and docking simulations. Results showed that the two drugs interaction with human serum albumin caused 19 F NMR signal shifted to diffe...
9 CitationsSource
#1Roche C. de Guzman (VT: Virginia Tech)H-Index: 9
#2Shanel M. Tsuda (VT: Virginia Tech)H-Index: 2
Last. Mark Van Dyke (VT: Virginia Tech)H-Index: 7
view all 6 authors...
Hair-derived keratin biomaterials composed mostly of reduced keratin proteins (kerateines) have demonstrated their utility as carriers of biologics and drugs for tissue engineering. Electrostatic forces between negatively-charged keratins and biologic macromolecules allow for effective drug retention; attraction to positively-charged growth factors like bone morphogenetic protein 2 (BMP-2) has been used as a strategy for osteoinduction. In this study, the intermolecular surface and bulk interact...
15 CitationsSource
#1Zari Hooshyar (PNU: Payame Noor University)H-Index: 13
#2Ghasem Rezanejade Bardajee (PNU: Payame Noor University)H-Index: 23
Last. Nastaran Dianatnejad (PNU: Payame Noor University)H-Index: 3
view all 6 authors...
Understanding the interaction between protein and manganese(II) Diamine sarcophagine (Mn(II)-DiAmsar) has significant implications for biological applications of Mn(II)-DiAmsar. To this aim, at first, Mn(II)-DiAmsar was synthesized and characterized. In the next step, the interaction between Mn(II)-DiAmsar and protein [human serum albumin (HSA) and bovine serum albumin (BSA)] was investigated by Fourier transform infrared (FT-IR), UV–Visible (UV–Vis), fluorescence spectroscopies, and cyclic volt...
11 CitationsSource
#1Fang Liu (NTU: Nanyang Technological University)H-Index: 89
#1Fang Liu (NTU: Nanyang Technological University)H-Index: 17
Last. Bengang XingH-Index: 53
view all 3 authors...
Human serum albumin (HSA), a major transport protein component in blood plasma, has been reported recently to play many important roles in pharmacotherapeutics development. Owing to its promising intrinsic binding capability of drug molecules, HSA offers favorable characteristics and can be directly used as its monomeric formula or can be fabricated into protein based nanoparticle platforms to realize the effective delivery of therapeutic molecules into targeted diseases areas. In addition, HSA ...
39 CitationsSource
Ontregeling van de activiteit van ‘matrix metalloproteinases’ (MMPs) en ‘a disintegrin and metalloproteinases’ (ADAMs) treedt op bij een groot aantal ziekten, waaronder ontstekingen en kanker. Het meten van de activiteit van MMPs en ADAMs in vivo op een niet-invasieve wijze door middel van radioactief gemerkte synthetische remmers en nucleaire beeldvorming, zou de mogelijkheid bieden om ontstekingshaarden en kanker beter te karakteriseren. Het doel van dit proefschrift is het ontwerp, de bereidi...