John W. Fenton II

Bedeutung für die Hirudotherapie

John W. Fenton II is an American biochemist whose published work relevant to hirudotherapy concerns the structure and function of α-thrombin, the enzyme that hirudin inhibits. In 'Thrombin active-site regions' (Seminars in Thrombosis and Hemostasis, 1986), written with D. H. Bing, he surveyed growing knowledge of the topographic features of α-thrombin and how these features define the enzyme's specificity and biological functions (PMID 3535077). The paper set out a dual characterisation. Thrombin is not merely an enzyme with moderately restricted proteolytic capability yet extraordinarily high specificity for certain bonds, such as the Aα-cleavage site in fibrinogen; it is also a protein with hormone-like activities involving cell-receptor interactions. These activities do not require the catalytically active enzyme but are blocked by hirudin, as by antithrombin III, and appear to involve a unique insertion and subsequent peptide segment at an exon junction. The enzymic functions, in contrast, depend on the catalytic site itself, deriving specificity from the adjacent apolar-binding site within the fibrinopeptide side and the independent anionic-binding site within the fibrin side of the active groove (PMID 3535077). Fenton was also a co-author of the 1990 paper that designed the hirulogs, the bivalent hirudin-derived thrombin inhibitors (PMID 2223763). ASH holds no verified record of his institutional appointments or of a role in the regulatory history of recombinant hirudin, and makes no such claims.