Salvatore Santamaria
Imperial College London
Matrix metalloproteinaseDocking (molecular)LRP1CellVersicanThrombospondinEnzymeChemistryAggrecanIn vitroAggrecanaseOsteoarthritisADAMTSProteaseDisintegrinActive siteCancer researchBiochemistryMetalloproteinaseStereochemistryCell cultureBiologyCell biology
43Publications
14H-index
584Citations
Publications 41
Newest
#1Salvatore Santamaria (Imperial College London)H-Index: 14
#2Doretta Cuffaro (UniPi: University of Pisa)H-Index: 5
Last. Josefin Ahnström (Imperial College London)H-Index: 16
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ADAMTS-5 is a major protease involved in the turnover of proteoglycans such as aggrecan and versican. Dysregulated aggrecanase activity of ADAMTS-5 has been directly linked to the etiology of osteoarthritis (OA). For this reason, ADAMTS-5 is a pharmaceutical target for the treatment of OA. ADAMTS-5 shares high structural and functional similarities with ADAMTS-4, which makes the design of selective inhibitors particularly challenging. Here we exploited the ADAMTS-5 binding capacity of β-N-acetyl...
4 CitationsSource
Commentary on 'Capivasertib restricts SARS-CoV-2 cellular entry: a potential clinical application for COVID-19' by Sun et al.
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#1Salvatore Santamaria (Imperial College London)H-Index: 14
#2Rens de Groot (UCL: University College London)H-Index: 9
Last. Rens de Groot (UCL: University College London)H-Index: 1
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The a disintegrin-like and metalloproteinase with thrombospondin motif (ADAMTS) family comprises 19 proteases that regulate the structure and function of extracellular proteins in the extracellular...
5 CitationsSource
#2Rens de GrootH-Index: 9
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#1Salvatore Santamaria (Imperial College London)H-Index: 14
#2Doretta Cuffaro (UniPi: University of Pisa)H-Index: 5
Last. Josefin Ahnstroem (Imperial College London)
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ADAMTS-5 is a major protease involved in the turnover of proteoglycans such as aggrecan and versican. Its aggrecanase activity has been directly linked to the etiology of osteoarthritis (OA), identifying ADAMTS-5 as a pharmaceutical target for OA treatment. However, most existing ADAMTS-5 inhibitors target its active site and therefore suffer from poor selectivity. Here, using a novel approach, we have designed a new class of sugar-based arylsulfonamide inhibitors, which are selective for ADAMTS...
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A Disintegrin And Metalloproteinase with ThromboSpondin motif (ADAMTS)-5 was identified in 1999 as one of the enzymes responsible for cleaving aggrecan, the major proteoglycan in articular cartilage. Studies in vitro, ex vivo and in vivo have validated ADAMTS-5 as a target in osteoarthritis (OA), a disease characterized by extensive degradation of aggrecan. For this reason, it attracted the interest of many research groups aiming to develop a therapeutic treatment for OA patients. However, ADAMT...
14 CitationsSource
: Biotinylation is a versatile technique that has been used to label proteins for a variety of applications. Under alkaline conditions, the N-hydroxylsuccinimide (NHS) ester present on the biotinylation reagent reacts with primary amines such as the side chain of lysine residues or the N-termini of proteins to yield stable amide bonds. However, the effect of biotinylation on enzyme structure and function has not been generally appreciated. In this chapter, I describe specific issues involving bi...
1 CitationsSource
#1Salvatore Santamaria (Imperial College London)H-Index: 14
#2Kazuhiro Yamamoto (University of Liverpool)H-Index: 17
: Aggrecan is a major matrix component of articular cartilage, and its dysregulated proteolysis is a crucial event in the pathogenesis of arthritis. Aggrecanases, members of ADAMTS family, play a pivotal role in aggrecan degradation with ADAMTS-4 and ADAMTS-5 being key enzymes. Cleavage events mediated by ADAMTSs are highly specific and very well characterized; therefore, it is possible to investigate aggrecanolysis by using antibodies reacting with the new N- and C-termini of the cleavage produ...
5 CitationsSource
#1Magdalena Gierula (Imperial College London)H-Index: 8
#2Isabelle I. Salles-Crawley (Imperial College London)H-Index: 6
Last. Josefin Ahnström (Imperial College London)H-Index: 16
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BACKGROUND: Activated protein C (APC)-mediated inactivation of factor (F)Va is greatly enhanced by protein S. For inactivation to occur, a trimolecular complex among FVa, APC, and protein S must form on the phospholipid membrane. However, direct demonstration of complex formation has proven elusive. OBJECTIVES: To elucidate the nature of the phospholipid-dependent interactions among APC, protein S, and FVa. METHODS: We evaluated binding of active site blocked APC to phospholipid-coated magnetic ...
5 CitationsSource
#1Salvatore Santamaria (Imperial College London)H-Index: 14
#2Kazuhiro Yamamoto (University of Liverpool)H-Index: 17
Last. Josefin Ahnström (Imperial College London)H-Index: 16
view all 8 authors...
ADAMTS (A Disintegrin-like and Metalloproteinase domain with Thrombospondin type 1 Motif)-1, -4 and -5 share the abilities to cleave large aggregating proteoglycans including versican and aggrecan. These activities are highly relevant to cardiovascular disease and osteoarthritis and during development. Here, using purified recombinant ADAMTS-1, -4 and -5, we quantify, compare, and define the molecular basis of their versicanase activity. A novel sandwich-ELISA detecting the major versican cleava...
11 CitationsSource