Disease relevance of S 2251

• In the human glioblastoma cell line, T-MG1, plasminogen activator activity (PA-activity) was demonstrated by using the chromogenic substrate S-2251 [1].
• The determination of blood fibrinolytic activity by synthetic chromogenic substrate S-2251 in patients with high risk of thromboembolism [2].

High impact information on S 2251

• The neutrophil-derived fraction inhibited tPA with plasminogen activity on S-2251 but not on H-D-isoleucyl-L-prolyl-L-arginine-p-nitroanilide (S-2288) [3].
• Both C5a inactivation and S-2251 cleavage were inhibited by the plasmin inhibitor alpha 2-antiplasmin, the urokinase inhibitor amiloride, and by anti-urokinase antibodies [4].
• Actins isolated from a variety of sources inhibited plasmin's hydrolysis of the synthetic substrate S-2251 in a noncompetitive manner, with a Ki of a 0.6-3.1 microM [5].
• In the presence of the peptides, the affinity of thrombin for the substrates S-2366 (pyro-Glu-Pro-Arg-4-nitroanilide), Chromozyme TH (tosyl-Gly-Pro-Arg-4-nitroanilide), and S-2251 (D-Val-Leu-Lys-4-nitroanilide) increased 1.5-2-fold with little change in the Vmax of substrate cleavage [6].
• The zymogen was readily self-activated during the refolding process to generate an active form (21 kDa) of hK4 (rhK4). rhK4 cleaved the chromogenic substrates Val-Leu-Arg-pNA (S-2266), Pro-Phe-Arg-pNA (S-2302), Ile-Glu-Gly-Arg-pNA (S-2222), and Val-Leu-Lys-pNA (S-2251), indicating that rhK4 has a trypsin-type substrate specificity [7].

Biological context of S 2251

• The inhibitory fraction had only a slight effect on urokinase with plasminogen- or plasmin-mediated fibrinolysis and no effect on urokinase- or plasmin-mediated cleavage of H-D-valyl-L-leucyl-L-lysine-p-nitroanilide (S-2251) [3].
• The kinetics of inhibition of the amidolytic activity of plasmin on D-Val-L-Leu-L-Lys p-nitroanilide hydrochloride (S-2251) by fibrinogen and fibrin were determined [8].
• Oleic acid-induced cleavage of this subunit containing the catalytic site of plasmin was suppressed by the plasmin substrate H-D-valyl-L-leucyl-L-lysine-p-nitroanilide (S-2251) and was prevented by alpha 2-antiplasmin [9].
• Activation procedures of plasminogen and subsequent assays of plasmin using a variety of substrates have been recently superseded by an assay which involves the formation of a plgn-SK complex which complex has an active site which hydrolyses the chromogenic substrate S-2251 [10].
• Various compounds were synthesized by combining three components at positions P1, P1' and P2'. Of these, N-(trans-4-aminomethylcyclohexanecarbonyl)-Tyr(O-2-bromobenzylo xycarbonyl)- octylamide inhibited plasmin selectively with IC50 values of 0.80 and 0.23 microM towards S-2251 and fibrin, respectively [11].

Anatomical context of S 2251

• An in vitro assay system, which measures the plasmin-mediated lysis of a chromogenic substrate, S-2251, was validated for use with granulosa cells of the hen to assess levels of both cell-associated and secreted PA [12].
• The plasminogen activator activity (PAA) in extracts of the intima, media, and adventitia of the normal human aorta and other large arteries (carotid artery, renal artery and iliac artery) was studied with a sensitive, quantitative spectrophotometric assay using plasminogen and the chromogenic plasmin substrate S-2251 [13].

Associations of S 2251 with other chemical compounds

• Heparin acted as a uncompetitive inhibitor of trypsin (Ki = 1.2 X 10(-6) M), plasmin (Ki = 4.9 X 10(-6) M) and urokinase (Ki = 1.0 X 10(-7) M) when Bz-Phe-Val-Arg-p-nitroanilide (S-2160), H-D-Val-Leu-Lys-p-nitroanilide (S-2251) and plasminogen, respectively, were used as substrates [14].
• Therapy was surveyed by daily measurement of the available plasminogen activity (aPl) with the chromogenic substrate S-2251 and by a modified bioassay, whereby the concentration of tranexamic acid was determined thrombelastographically and expressed as antifibrinolytic equivalent [15].
• When Glu-plg I and II were activated by urokinase (UK) and the hydrolysis of S-2251 was measured, the extent of hydrolysis increased in the presence of t-x and 6AHA [16].
• One of bovine preparations had the highest amidolytic activity toward synthetic substrates S-2238 and S-2251 and also showed fibrinolytic activity when tested with the plasminogen-free fibrin plate method [17].
• Plasminogen kringle 1+2+3 (K1-3) containing lysine-binding sites inhibited the reaction of plasmin with alpha 2-plasmin inhibitor (alpha 2PI), in a rate assay using a synthetic chromogenic substrate, S-2251 [18].

Gene context of S 2251

• Secreted and cell-associated PA activity was measured by its ability to activate plasminogen into plasmin, that is, by the release of paranitroaniline from the plasmin synthetic substrate S-2251 [19].
• When the amounts of added tPA and analogues were standardized so that each generated the same absorbance in a chromogenic assay containing S-2251, plasminogen, and fibrinogen fragments, there was a significant difference in the way in which the analogues were titrated by the inhibitor [20].
• The assay is based on plasminogen activation by low-M(r) u-PA and subsequent cleavage of the plasmin-specific tripeptide substrate, S-2251 [21].
• LV-Ka exhibits substrate specificities not only for the glandular kallikrein H-D-Val-Leu-Arg-pNA (S-2266) but also for the plasmin substrates S-2251 and Tos-Gly-Pro-Lys-pNA [22].
• Fn and Fg-CNBr had no effect on the reaction of miniplasmin with S-2251, alpha 2AP or alpha 2M [23].

Analytical, diagnostic and therapeutic context of S 2251

• Chromogenic peptide (S-2251) microassay was used for a quantitative estimation of the PA activity in conditioned medium and enzyme-linked immunosorbent assay (ELISA) for tissue plasminogen activator concentration [24].
• The material contained none of the known plasma proteinase inhibitors when studied by crossed-immunoelectrophoresis and electroimmunoassay, but inhibited a clot-lysis-time assay and an esterolytic assay that used the synthetic substrate S-2251 (D-Val-Leu-Lys-p-nitroanilide) [25].
• Sweat was concentrated x 50 by ultrafiltration, and its PA activity determined by the two-step assay method (conversion of plasminogen to plasmin with the subsequent assay of plasmin activity using the substrate S-2251) [26].
• SDS-PAGE confirmed that the enhancement of the hydrolysis of S-2251 by the mixture of Glu-plg, sct-PA and HHS-5 was due to the facilitation of the conversion of Glu-plg to plasmin [27].
• 0. The activation rate and conformational changes of such acid-treated plg were measured using the hydrolysis of S-2251, spectrofluorometry and spectropolarimetry (circular dichroism) [28].

References