Salvatore Santamaria
Imperial College London
Matrix metalloproteinaseDocking (molecular)LRP1VersicanThrombospondinEnzymeChemistryAggrecanIn vitroAggrecanaseOsteoarthritisADAMTSProteaseDisintegrinProteolysisActive siteCancer researchBiochemistryMetalloproteinaseStereochemistryBiologyCell biology
43Publications
14H-index
584Citations
Publications 40
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...
1 CitationsSource
#1Salvatore Santamaria (Imperial College London)H-Index: 14
#2Rens de Groot (UCL: University College London)H-Index: 1
Last. Rens de Groot (UCL: University College London)H-Index: 9
view all 2 authors...
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...
1 CitationsSource
#2Rens de GrootH-Index: 9
Source
#1Salvatore Santamaria (Imperial College London)H-Index: 14
#2Doretta Cuffaro (UniPi: University of Pisa)H-Index: 5
Last. Josefin Ahnstroem (Imperial College London)
view all 10 authors...
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...
Source
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...
11 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...
9 CitationsSource
#1Alain Colige (University of Liège)H-Index: 12
#1Alain Colige (University of Liège)H-Index: 50
Last. Rens de Groot (Imperial College London)H-Index: 9
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: The protease ADAMTS7 functions in the extracellular matrix (ECM) of the cardiovascular system. However, its physiological substrate specificity and mechanism of regulation remain to be explored. To address this, we conducted an unbiased substrate analysis using terminal amine isotopic labeling of substrates (TAILS). The analysis identified candidate substrates of ADAMTS7 in the human fibroblast secretome, including proteins with a wide range of functions, such as collagenous and noncollagenous...
7 CitationsSource